in the above definition of formula i , halogen is fluorine , chlorine , bromine or iodine . preferred halogens are fluorine and chlorine . c 1 - c 4 alkyl is , for example , methyl , ethyl , propyl , 1 - methylethyl , n - butyl , 1 - methylethyl , isopropyl , 1 , 1 - dimethylethyl , 1 - methylpropyl , 2 - methylpropyl , cyclopropyl and cyclobutyl . preferred alkyls are methyl and ethyl . examples of ar groups include , 4 - fluorophenyl , 2 - 4 - difluorophenyl , 2 , 4 , 6 - trifluorophenyl , 4 - chlorophenyl , 2 , 4 - dichlorophenyl , 2 , 4 , 6 - trichlorophenyl , 4 - trifluoromethylphenyl and 4 - trifluoromethoxyphenyl . preferred ar groups are phenyl group having 1 or 2 substituents each independently selected from fluorine , chlorine , trifluoromethyl and trifluromethoxy . most preferably , ar is 2 , 4 - difluorophenyl , 2 , 4 - dichlorophenyl , 4 - trifluromethylphenyl or 4 - trifluoromethoxyphenyl . examples of 5 - or 6 - membered monocyclic rings are 1 - pyrrolyl , 2 - pyrrolyl , 3 - pyrrolyl , 2 - furyl , 3 - furyl , 2 - thienyl , 3 - thienyl , 1 - imidazolyl , 4 - imidazolyl , 1 - pyrazolyl , 3 - pyrazolyl , 4 - pyrazolyl , 5 - pyrazolyl , 1 -( 1h )- 1 , 2 , 4 - triazolyl , 3 -( 1h )- 1 , 2 , 4 - triazolyl , 3 -( 4h )- 1 , 2 , 4 - triazolyl , 5 -( 1h )- 1 , 2 , 4 - triazolyl , 4 -( 4h )- 1 , 2 , 4 - triazolyl , 1 , 2 , 3 - triazolyl , 2 - oxazolyl , 4 - oxazolyl , 5 - oxazolyl , 2 - thiazolyl , 4 - thiazolyl , 5 - thiazolyl , 1 , 2 , 4 - oxadiazol - 3 - yl , 1 , 2 , 4 - oxadiazol - 5 - yl , 1 , 3 , 4 - oxadiazol - 2 - yl , 1 , 2 , 4 - thiadiazol - 3 - yl , 1 , 2 , 4 - thiadiazol - 5 - yl , 1 , 3 , 4 - thiadiazol - 2 - yl , 5 -( 1h )- tetrazolyl , 5 -( 2h )- tetrazolyl , 2 - pyridyl , 3 - pyridyl , 4 - pyridyl , 2 - pyrimidyl , 4 - pyrimidyl and 5 - pyrimidyl . examples of 8 - to 10 - membered bicyclic heterocycle groups are 2 - benzimidazolyl , 5 - benzimidazolyl , 2 - benzoxazolyl , 5 - benzoxazolyl , 6 - benzoxazolyl , 2 - benzothiazolyl , 5 - benzothiazolyl , 6 - benzothiazolyl , imidazolo [ 4 , 5 - b ] pyridin - 2 - yl , imidazolo [ 4 , 5 - b ] pyridin - 5 - yl , oxazolo [ 5 , 4 - b ] pyridin - 2 - yl , oxazolo [ 5 , 4 - b ] pyridin - 5 - yl , oxazolo [ 5 , 4 - b ] pyridin - 6 - yl , thiazolo [ 5 , 4 - b ] pyridin - 2 - yl , thiazolo [ 5 , 4 - b ] pyridin - 5 - yl and thiazolo [ 5 , 4 - b ] pyridin - 6 - yl . triazolone - yl may be 2 - or 5 - substutitued 1 , 2 , 4 - triazol - 3 - one , such as 2h - 1 , 2 , 4 - triazol - 3 - one - 4 - yl or 4h - 1 , 2 , 4 - triazol - 3 - one - 2 - yl . examples of r 1 include hydrogen , methyl , ethyl , propyl , hydroxymethyl , alkoxymethyl , fluoromethyl and trifluoromethyl . preferably , r 1 is alkyl . most preferably , r 1 is methyl . examples of r 2 include hydrogen , methyl , ethyl , propyl , hydroxymethyl , alkoxymethyl , fluromethyl and trifluoromethyl . preferably , r 2 is hydrogen . depending on the substituents in formula i , the compound may have one or more than one asymmetric centers , resulting in possible stereoisomers . this invention relates to single individual isomers as well as mixture of isomers . when r 1 and r 2 are the same , formula i has one asymmetric center and there are two possible isomers , i . e . 2r and 2s isomers . this invention relates to mixtures as well as individual isomers . the most preferable isomer is the 2r isomer . when r 1 and r 2 are different , formula i has two asymmetric centers , and there are four possible isomers , i . e . 2r , 3r ; 2r , 3s ; 2s , 3r and 2s , 3s . this invention relates to the mixture of isomers as well as individual isomers . the most preferred isomer in this situation is 2r , 3r . it is more preferred that r 7 is a group ## str4 ## wherein r is as described above , and most preferred that the other groups additionally are as follows : ar is 2 , 4 - difluorophenyl , r 1 is methyl , and r 2 through r 6 are each hydrogen . specifically , the more preferred embodiments of the present invention include the compounds that are disclosed in table 3 . those disclosed in example nos . 36 - 51 are more preferred , with example nos . 43 , 47 , 50 and 51 being the most preferred . the compounds of formula i can be prepared by a convergent approach from the epoxide of formula ii and the piperazino compound of formula iii ( see scheme 1 ). the epoxides were prepared following the synthetic routes described in the literature ( chem . pharm . bull ., 1993 , 41 , 1035 - 1042 ). the synthetic routes for the preparation of certain piperazino compounds of the formula iii are disclosed in schemes 4 - 6 and 8 . the scheme 7 describes a linear synthetic route for preparing certain compounds of formula i . the epoxide of formula ii and the piperazino compound of formula iii were reacted in the presence of base such as sodium carbonate , potassium carbonate , cesium carbonate and the like . this reaction was also performed in the presence of lithium perchlorate and sodium perchlorate . the suitable solvents were chosen from acetonitrile , dmf , dmso , thf , dichloromethane , chloroform , methanol , ethanol , isopropanol and tert - butanol . the most preferred solvents were dmf and acetonitrile . the temperature of the reaction varied from 60 - 180 ° c ., depending on the solvent and reactants . the most preferred temperature was 80 - 140 ° c . the reactants were allowed to react to the completion or near to the completion of the reaction . the length of reaction time varied from few hours to several hours depending on the reactants , temperature , and the solvent . ## str5 ## certain compounds of formula i were prepared from a common intermediate , which forms example 2 of this invention as described in scheme 3 . example 2 was prepared from epoxide iv by two synthetic routes as depicted in scheme 2 . in the first route , a 1 : 1 molar ratio of epoxide and ethyl piperazine - 1 - carboxylate were reacted in the presence of potassium carbonate or lithium perchlorate in a suitable solvent . the obtained ester was hydrolysed with strong base such as sodium hydroxide or potassium hydroxide to give piperazinyl compound 2 . in this reaction the resulting n - carboxylic acid undergoes in - situ decarboxylation to give the piperazino compound 2 . in an alternate route , the piperazino compound was obtained in a single step from the reaction of epoxide iv with piperazine . in a typical procedure , the epoxide and excess piperazine were reacted in the presence of lithium perchlorate in a suitable solvent and at a desired temperature . certain compound of formula i wherein x is co , so 2 , cs , or -- n ═ n -- were prepared as described in scheme 3 . the compounds of formula i wherein x is co were produced from the reaction of piperazinyl compound 2 with acid chloride ( r 7 cocl ) in the presence of a base such as triethylamine , n - methylmorpholine , n , n - diisopropylethylamine . the reaction was carried out in an inert solvent at - 20 ° c . to 80 ° c . the most preferred solvents were dichloromethane , chloroform , tetrahydrofuran and acetonitrile . most preferably the reaction was carried out at 0 - 25 ° c . certain compounds of formula i wherein x is so 2 were prepared from the reaction of 2 and r 7 -- so 2 -- cl . in these reactions , r 7 is as described above . certain compounds of formula i wherein x is co or cs and r 7 is or were prepared from the reaction of piperazinyl compound 2 and isocyanates and isothiocyanates . in a typical reaction , a 1 : 1 molar ratio of compound and isocyanate or isothiocyanate were reacted in a suitable solvent at - 15 to 45 ° c . the preferred solvents were acetonitrile , ethyl acetate and dichloromethane . the preferred temperature was 0 to 25 ° c . the reaction time varied from few hours to several hours depending on the reactants , solvent and temperature . ## str6 ## the reaction of 1h or 2h - 1 , 2 , 4 - triazol - 3 - diazonium salt with the piperazinyl compound 2 gave the n - azo compound of formula viii . this reaction was conducted at suitable temperature in suitable solvent in the presence of base like sodium hydroxide , potassium hydroxide and potassium carbonate . certain compounds of formula i wherein x is bond and r 7 is unsubstituted or substituted azole were prepared according to scheme 1 the synthetic routes followed for the preparation of piperazinyl azoles x , xi , xii , xiii and xvi are described in schemes 4 - 6 . in a typical procedure , piperazinyl azole and epoxide were heated in a suitable solvent in the presence of lithium perchlorate or potassium carbonate for 24 - 48 h . the molar ratio of the reactants varied from 1 : 1 to 1 : 5 . after usual workup the product was purified by column chromatography . ## str7 ## certain compounds of formula i wherein x is a bond and r 7 is a 4 -[ 2 - substituted - 1 , 2 , 4 - triazol - 3 - one - 4 - yl ] phenyl group were prepared in two independent synthetic routes . the first route involves the linear approach as described in scheme 7 . the intermediates formed during this synthesis are compounds of formula i , wherein x is bond and r 7 is phenyl group with substitution . ## str8 ## the second synthetic route involves a more efficient convergent approach ( scheme 1 ). in a typical procedure , an appropriate epoxide of formula ii and an appropriate piperazinyl derivative xxiii were reacted in the presence of lithium perchlorate in a suitable solvent and at a suitable temperature . the reactants were allowed to react to the completion of the reaction . the reaction time varied from few hours to several hours depending on the reactants . the epoxides used in this invention are known and were prepared by following the reported procedures . the piperazino compounds of formula xxiii were prepared as described in scheme 8 . ## str9 ## pharmaceutically acceptable salts of formula i were prepared by mixing the solution of the free base with excess of acid at 0 - 25 ° c . the precipitated salt was collected by filtration . in some cases the solvent was evaporated to dryness and the resulting crude salt was recrystallized in a suitable solvent . for the preparation of these acid addition salts , acids were selected from hydrochloric acid , hydrobromic acid , sulphuric acid , tartaric acid , succinic acid , fumaric acid , methanesulphonic acid or p - toluenesulphonic acid . the compounds of the present invention were evaluated in vitro for their antifungal activity and were assessed based on minimum inhibitory concentration of the test compound , i . e . the concentration of the test compound at which growth of particular organism fails to occur . the mic was determined after incubating the test compound with the strain for 48 h at 37 ° c . in an appropriate medium . the microorganisms used in this test include candida albicans , c . tropicalis , c . kefyr , c . krusei , c . guilliermondii , c . glabrata , cryptococcus neoformans , aspergillus niger and a . fumigatus . in vitro data of certain representative compounds is provided in the following table . table 1__________________________________________________________________________in vitro activity of compounds of formula i mic of compounds of formula i , μg / mlfungal fluco - itraco - strains # 36 # 40 # 41 # 42 # 43 # 44 # 46 nazole nazole__________________________________________________________________________candida 0 . 09 0 . 09 0 . 09 0 . 09 0 . 048 0 . 048 0 . 048 0 . 78 0 . 09albicansc . tropicalis 0 . 09 0 . 048 0 . 09 0 . 09 0 . 048 0 . 048 0 . 048 0 . 39 0 . 09c . kefyr 0 . 048 0 . 048 0 . 48 0 . 048 0 . 048 0 . 048 0 . 048 0 . 39 0 . 09c . krusei 0 . 09 0 . 19 1 . 56 1 . 56 0 . 09 0 . 09 0 . 19 50 0 . 39c . guillier - 0 . 048 0 . 048 0 . 048 0 . 09 0 . 09 0 . 048 0 . 048 1 . 56 0 . 19mondiic . glabrata 0 . 09 0 . 39 0 . 78 12 . 5 0 . 78 1 . 56 0 . 39 12 . 5 0 . 19cryptococcus 0 . 048 0 . 48 0 . 48 0 . 19 0 . 048 0 . 048 0 . 048 1 . 56 0 . 39neoformanssaccheromyces 0 . 19 0 . 09 0 . 19 0 . 39 0 . 09 0 . 048 0 . 09 6 . 25 0 . 39cerevisiaea . niger 0 . 78 0 . 78 3 . 12 3 . 12 0 . 19 0 . 19 0 . 09 & gt ; 100 0 . 39aspergillus 0 . 39 0 . 39 0 . 78 0 . 39 0 . 19 0 . 048 0 . 048 & gt ; 100 0 . 19fumigatus__________________________________________________________________________ certain selected compounds were evaluated in - vivo for their antifungal efficacy . series of doses of test compounds were administered by oral , i . v and s . c . routes to infected mice , i . e mice that are inoculated with a strain of candida albicans or aspergillus fumigatus . efficacy of test compound was determined based on survival of treated mice compared to control . the in vivo efficacy was assessed based on ed 50 of the test compound . the following table provides ed 50 of certain compounds for systemic infections of c . albicans and a . fumigatus in mice models . table 2______________________________________in - vivo activity of compounds of formula i therapeutic efficacy ( ed . sub . 50 mg / kg ) in mice systemic infectinonsexample # c . albicans a . fumigatus______________________________________36 8 . 01 & gt ; 4540 4 . 68 67 . 0541 8 . 01 89 . 2842 & gt ; 90 71 . 1443 1 . 57 42 . 346 56 . 02 & gt ; 45______________________________________ the compounds of formula i and their salts are antifungal agents , useful to treat or prevent topical , lung invasive , as well as systemic fungal infections in mammals including humans . for example they are useful in treating topical infections in man caused by species of candida , trichophyton , microsporum , mucosal infections caused by species of candida , and systemic infections caused by species of candida , aspergillus , cryptococcus , pneumocystis , histoplasma or blastomyces . the above compounds have shown impressive in vivo efficacy against mice systemic candidiosis , systemic aspergillosis and lung invasive aspergillosis . when the compounds of the present invention or their pharmaceutically acceptable salts are used for treatment or prophylaxis of fungal infections in mammals including humans , they can be administered alone , but generally it is more preferred to administer the compounds in a pharmaceutical formulation . this formulation varies with intended route of administration . for example the compounds can be administered orally in the form of tablets , coated tablets , capsules , suspensions , solutions and the like . these oral preparations which contain the present compounds are prepared with excipients , binders , coloring agents , flavors , etc . which can be formulated in a manner known in the art . the present compounds can be injected parenterally , for example intravenously , intramuscularly or subcutaneously . these injections are sterile aqueous solutions which contain the antifungal agent with other substances , such as salts , glucose or an isotonic agent , and can be formulated in a conventional manner . the amount of the present compounds incorporated into the pharmaceutical composition varies depending on the physical and chemical properties of the drug , dosage and route of administration . preferably the oral formulations are prepared with 1 to 25 % ( w / w ) antifungal agent and the injection formulation is prepared with 0 . 1 to 5 % ( w / w ) of antifungal agent . alternatively , the antifungal agents also can be administered in the form of a suppository or pessary , or they may be applied topically in the form of lotion , solution , ointment , cream or dusting powder . suppositories and ointments which contain 1 - 10 % of active ingredient with a base , stabilizer or surfactant can be prepared in a conventional manner . the dosage of the compound of formula i or its pharmaceutically acceptable salt can be suitably determined depending on the indivdual cases , taking symptoms , age , sex , disease status , patient condition , route of administration and the like into consideration . usually the dosage can be 0 . 01 - 20 mg / kg in single or divided daily doses . table 3__________________________________________________________________________ ## str10 ## example # r . sub . 3 r . sub . 5 x -- r . sub . 7 configuration at c . sub . 2 and__________________________________________________________________________ c . sub . 3 1 h h -- cooet r , r 2 h h -- h r , r 3 h h -- cn r , r 4 h h -- cho r , r 5 -- ch . sub . 3 -- ch . sub . 3 -- h r , r 6 -- ch . sub . 3 -- ch . sub . 3 -- cooet r , r 7 h h ## str11 ## r , r__________________________________________________________________________ ## str12 ## example # x -- r . sub . 7 configuration at c . sub . 2 and__________________________________________________________________________ c . sub . 3 8 ## str13 ## r , r 9 ## str14 ## r , r10 ## str15 ## r , r11 ## str16 ## r , r12 ## str17 ## r , r13 ## str18 ## r , r14 ## str19 ## r , r15 ## str20 ## r , r16 ## str21 ## r , r17 ## str22 ## r , r18 ## str23 ## r , r19 ## str24 ## r , r20 ## str25 ## r , r21 ## str26 ## r , r22 ## str27 ## r , r23 ## str28 ## r , r__________________________________________________________________________ configuration atexample # x = bond ; r . sub . 7 c . sub . 2 and c . sub . 3__________________________________________________________________________24 ## str29 ## r , r25 ## str30 ## r , r26 ## str31 ## r , r27 ## str32 ## r , r28 ## str33 ## r , r29 ## str34 ## r , r30 ## str35 ## r , r31 ## str36 ## r , r32 ## str37 ## r , r33 ## str38 ## r , r34 ## str39 ## r , r35 ## str40 ## r , r36 ## str41 ## r , r37 ## str42 ## s , r38 ## str43 ## s , s39 ## str44 ## r , s40 ## str45 ## r , r41 ## str46 ## r , r42 ## str47 ## r , r43 ## str48 ## r , r44 ## str49 ## r , r45 ## str50 ## r , r46 ## str51 ## r , r47 ## str52 ## r , r48 ## str53 ## r , r49 ## str54 ## r , r50 ## str55 ## r , r51 ## str56 ## r , r__________________________________________________________________________ a mixture of ( 2r , 3s )- 2 -( 2 , 4 - difluorophenyl )- 3 - methyl - 2 -( 1h - 1 , 2 , 4 - triazol - 1 - yl ) methyloxirane iv ( 1 . 0 g , 4 . 0 mmol ), ethyl piperazine - 1 - carboxylate ( 1 . 2 ml , 8 mmol ) and potassium carbonate in dmf ( 5 ml ) was heated at 120 ° c . for 18 h . after cooling the reaction mixture was poured onto crushed ice and extracted with ethyl acetate ( 3 × 30 ml ). the combined extract was washed with water , brine , dried ( mgso 4 ) and concentrated and the resulting product was purified on a column of silica gel ( hexane / etoac , 1 : 1 ) to give the title compound as off - white solid ( 400 mg , 24 %). 1 h nmr ( cdcl 3 ) δ : 0 . 90 ( d , 3h , ch 3 ), 1 . 26 ( t , 3h , ch 3 ), 2 . 31 - 2 . 49 ( m , 2h , ch 2 ), 2 . 78 - 3 . 07 ( m , 3h , ch 2 and ch ), 3 . 40 - 3 . 59 ( m , 4h , 2xch 2 ), 4 . 15 ( q , 2h , och 2 ), 4 . 9 ( ab q , 2h , ch 2 ), 5 . 05 ( s , 1h , oh ), 6 . 66 - 6 . 84 ( m , 2h , ar -- h ), 7 . 36 - 7 . 51 ( m , 1h , ar -- h ), 7 . 78 ( s , 1h , het - h ), 7 . 92 ( s , 1h , het - h ). fab - ms : 410 . 2 ( mh + ), calcd . c 19 h 25 f 2 n 5 o 3 409 . 44 . a mixture of ( 2r , 3s )- 2 -( 2 , 4 - difluorophenyl )- 3 - methyl - 2 -( 1h - 1 , 2 , 4 - triazol - 1 - yl ) methyloxirane ( 1 . 0 g , 4 . 0 mmol ), piperazine ( 860 mg , 10 mmol ) and lithium perchlorate ( 625 mg , 6 mmol ) in acetonitrile ( 15 ml ) was heated under reflux for 48 h . the solvent was removed under reduced pressure , the residue was treated with crushed ice and extracted with ethylacetate ( 3 × 30 ml ). the combined organic extract was washed with water , brine , dried ( na 2 so 4 ) and concentrated to give the title compound as thick viscous gum ( 1 . 5 g , 78 %). the title compound was also prepared by hydrolysis of 2r , 3r - 2 -( 2 , 4 - difluorophenyl )- 3 -( 4 - ethoxycarbonylpiperazin - 1 - yl )- 1 -( 1h - 1 , 2 , 4 - triazol - 1 - yl ) butan - 2 - ol 1 with 2m sodium hydroxide solution . 1 h nmr ( cdcl 3 ) δ : 0 . 97 ( d , 3h , ch 3 ), 2 . 32 - 2 . 42 ( m , 2h , ch 2 ), 2 . 66 - 2 . 90 ( complex , 8h , 3xch 2 , ch and nh ), 4 . 85 ( ab q , 2h , ch 2 ), 6 . 68 - 6 . 83 ( m , 2h , ar -- h ), 7 . 42 - 7 . 55 ( m , 1h , ar -- h ), 7 . 78 ( s , 1h , het - h ), 8 . 0 ( s , 1h , het - h ). fab - ms : 338 . 1 ( mh + ), calcd . c 16 h 21 f 2 n 5 o 337 . 38 . to a cooled ( 0 ° c .) mixture of ( 2r , 3r )- 2 -( 2 , 4 - difluorophenyl )- 3 -( piperazin - 1 - yl )- 1 -( 1h - 1 , 2 , 4 - triazol - 1 - yl ) butan - 2 - ol 2 ( 250 mg , 0 . 74 mmol ) and triethylamine ( 0 . 42 ml , 3 mmol ) in acetonitrile ( 15 ml ) was added cyanogen bromide ( 160 mg , 1 . 5 mmol ) in acetonitrile ( 0 . 5 ml ). the reaction mixture was stirred at room temperature for 18 h . the solvent was removed under reduced pressure . to the resulting residue water was added and extracted with ethyl acetate ( 3 × 20 ml ). the combined organic extract was washed with water , brine and dried over magnesium sulphate . the solvent was removed and the product was purified on a column of silica gel ( hexane / etoac , 1 : 1 ) to give the title compound as a colorless solid ( 150 mg , 56 %). 1 h nmr ( cdcl 3 ) δ : 0 . 89 ( d , 3h , ch 3 ), 2 . 52 - 2 . 61 ( m , 2h , ch 2 ), 3 . 0 - 3 . 31 ( m , 7h , 3xch 2 and ch ), 4 . 88 - 4 . 91 ( m , 3h , ch 2 and oh ), 6 . 66 - 6 . 78 ( m , 2h , ar -- h ), 7 . 3 - 7 . 5 ( m , 1h , ar -- h ), 7 . 78 ( s , 1h , het - h ), 7 . 87 ( s , 1h , het - h ). fab - ms : 363 . 0 ( mh + ), calcd . c 17 h 20 f 2 n 6 o 362 . 39 . a mixture of compound 2 ( 200 mg , 0 . 6 mmol ) and potassium carbonate ( 248 mg , 1 . 8 mmol ) in dmf ( 5 ml ) was heated at 120 ° c . for 24 h . the contents were poured into cold water and extracted with ethyl acetate ( 3 × 20 ml ). the combined organic extract was washed with water , brine and dried over sodium suphate . the solvent was removed under reduced pressure and the resulting product was purified on a column of silica gel ( etoac / meoh ; 98 : 2 ) to give the title compound as colorless solid ( 80 mg , 36 %). 1 h nmr ( cdcl 3 ) δ : 0 . 90 ( d , 3h , ch 3 ), 2 . 44 - 2 . 52 ( m , 2h , ch 2 ), 2 . 93 - 3 . 11 ( m , 3h , ch 2 and ch ), 3 . 39 - 3 . 59 ( m , 4h , 2xch 2 ), 4 . 93 - 4 . 97 ( m , 3h , ch 2 and oh ), 6 . 66 - 6 . 81 ( m , 2h , ar -- h ), 7 . 36 - 7 . 48 ( m , 1h , ar -- h ), 7 . 79 ( s , 1h , het - h ), 7 . 91 ( s , 1h , het - h ), 8 . 02 ( s , 1h , cho ). fab - ms : 366 . 1 ( mh + ), calcd . c 17 h 2 lf 2 n 5 o 2 365 . 39 . the title compound 5 was obtained as a thick viscous oil in 58 % yield from the reacton of ( 2r , 3s )- 2 -( 2 , 4 - difluorophenyl )- 3 - methyl - 2 -( 1h - 1 , 2 , 4 - triazol - 1 - yl ) methyloxirane iv and 2 , 5 - dimethylpiperazine , by a similar method described in example 2 . 1 h nmr ( cdcl 3 ) δ : 0 . 85 - 0 . 96 ( 3 d merged , 9h , 3xch 3 ), 1 . 85 - 1 . 96 ( m , 2h ), 2 . 4 - 2 . 59 ( m , 2h ), 2 . 64 - 2 . 96 ( m , 3h ), 3 . 27 - 3 . 38 ( m , 1h ), 4 . 81 ( ab q , 2h , ch 2 ), 5 . 50 ( brs , 1h , oh ), 6 . 69 - 6 . 84 ( m , 2h , ar -- h ), 7 . 45 - 7 . 58 ( m , 1h , ar -- h ), 7 . 81 ( s , 1h , het - h ), 8 . 02 ( s , 1h , het - h ). fab - ms : 366 . 1 ( mh + ), calcd . cl 8 h 2 , f 2 n , o 365 . 43 . to a mixture of compound 5 ( 228 mg , 0 . 62 mmol ) and triethylamine ( 0 . 18 ml , 1 . 24 mmol ) in dichloromethane ( 10 ml ) at 0 ° c . was added dropwise ethyl chloroformate ( 135 mg , 1 . 24 mmol ) in dichloromethane ( 3 ml ). the reaction mixture was stirred at 0 ° c . for 30 minutes and 1 h at room temperature . the contents were diluted with 30 ml of dichloromethane , washed with water , brine and dried over magnesium sulphate . the solvent was removed under reduced pressure and the resulting oil was chromatographed on a column of silica gel . elution with hexane / etoac ( 1 : 1 ) gave the title compound as an off - white solid ( 210 mg , 80 %). 1 h nmr ( cdcl 3 ) δ : 0 . 94 ( d , 3h , ch 3 ), 1 . 07 - 1 . 10 ( m , 6h , 2xch 3 ), 1 . 28 ( t , 3h , ch 3 ), 2 . 34 - 2 . 46 ( m , 1h ), 2 . 76 - 2 . 82 ( m , 1h ), 2 . 96 - 3 . 09 ( m , 2h ), 3 . 21 - 3 . 31 ( m , 1h ), 3 . 67 ( m , 1h ), 3 . 98 - 4 . 27 ( m , 3h ), 4 . 80 ( ab q , 2h ), 5 . 13 ( s , 1h , oh ), 6 . 67 - 6 . 82 ( m , 2h , ar -- h ), 7 . 39 - 7 . 52 ( m , 1h , ar -- h ), 7 . 78 ( s , 1h , het - h ), 7 . 94 ( s , 1h , het - h ). fab - ms : 438 . 3 ( mh + ), calcd . c 21 h 29 f 2 n 5 o 3 437 . 49 . to a mixture of compound 2 ( 150 mg , 0 . 44 mmol ) and triethylamine ( 1 . 0 ml , 0 . 72 mmol ) in dichloromehane ( 15 ml ) was added di - tert - butyldicarbonate ( 110 mg , 0 . 48 mmol ) at ° c . the reaction mixture was stirred for 1 h at 0 ° c . and 3 h at room temperature . then diluted with chloroform ( 20 ml ), washed with water , brine and dried over sodium sulphate . the solvent was removed under reduced pressure and the resulting product was purified on a column of silica gel ( etoac / hexane ) to give the title compound as a colorless solid ( 160 mg , 82 %). 1 h nmr ( cdcl 3 ) δ : 0 . 92 ( d , 3h , ch 3 ), 1 . 46 ( s , 9h , 3xch 3 ), 2 . 34 - 2 . 40 ( m , 2h , ch 2 ), 2 . 79 - 2 . 92 ( m , 2h , ch 2 ), 2 . 97 ( m , 1h , ch ), 3 . 43 ( m , 4h , 2xch 2 ), 4 . 88 ( ab q , 2h , ch 2 ), 5 . 11 ( s , 1h , oh ), 6 . 66 - 6 . 80 ( m , 2h , ar -- h ), 7 . 38 - 7 . 51 ( m , 1h , ar -- h ), 7 . 78 ( s , 1h , het - h ), 7 . 94 ( s , 1h , het - h ). fab - ms 438 . 2 ( mh + ); calcd . c 21 h 29 f 2 n 5 o 3 437 . 49 . to a ice cooled solution of ( 2r , 3r )- 2 -( 2 , 4 - diflurophenyl )- 3 -( piperazin - 1 - yl )- 1 -( 1h - 1 , 2 , 4 - triazole - 1 - yl ) butan - 2 - ol 2 ( 150 mg , 0 . 44 mmol ) in acetonitrile ( 10 ml ) was added phenylisocyanate ( 60 mg , 0 . 5 mmol ) in acetonitrile ( 4 ml ). the reaction mixture was stirred at 0 ° c . for 2 h , diluted with 20 ml of ethyl acetate and successively washed with water , brine and dried over sodium sulphate . this organic extract was concentrated and the residue was purified by passing through a column of silica gel ( hexane / etoac ) to give the title compound as a colorless solid ( 170 mg , 84 %). 1 h nmr ( cdcl 3 ) δ : 0 . 92 ( d , 3h , ch 3 ), 2 . 5 ( m , 2h , ch 2 ), 3 . 02 ( m , 3h , ch 2 and ch ), 3 . 52 ( m , 4h , 2xch 2 ), 4 . 8 - 5 . 1 ( ab q and s merged , 3h , ch 2 and oh ), 6 . 31 ( brs , 1h , nh ), 6 . 65 - 6 . 85 ( m , 2h , ar -- h ), 7 . 0 - 7 . 1 ( m , 1h , ar -- h ), 7 . 25 - 7 . 5 ( m , 5h , ar -- h ), 7 . 78 ( s , 1h , het - h ), 7 . 92 ( s , 1h , het - h ). ms ( fab ): 457 . 0 ( mh + ), calcd . c 23 h 26 f 2 n 6 o 2 456 . 49 . the tiltle compound was prepared similarly to example 8 starting from same piperazine derivative and ethylisocyanate . the product was obtained as a colorless solid in 75 % yield . 1 h nmr ( cdcl 3 ) δ : 0 . 9 ( d , 3h , ch 3 ), 1 . 14 ( t , 3h , ch 3 ), 2 . 42 ( m , 2h , ch 2 ), 2 . 8 - 3 . 1 ( m and q merged , 3h , ch 2 and ch ), 3 . 2 - 3 . 5 ( m , 6h , 3xch 2 ), ( 4 . 4 brs , 1h , nh ), 4 . 88 ( ab q , 2h , ch 2 ), 5 . 06 ( s , 1h , oh ), 6 . 7 - 6 . 9 ( m , 2h , ar -- h ), 7 . 45 ( m , 1h , ar -- h ), 7 . 78 ( s , 1h , het - h ), 7 . 93 ( s , 1h , het - h ). fab - ms : 409 . 1 ( mh + ), calcd . c 19 h 26 f 2 n 6 o 2 408 . 45 . the title compound was prepared similarly to example 8 starting from same piperazine derivative 2 and phenylisothiocyanate . the product was obtained as a colorless solid in 80 % yield . 1 h nmr ( cdcl 3 ) δ : 0 . 88 ( d , 3h , ch 3 ), 2 . 5 ( m , 2h , ch 2 ), 2 . 9 - 3 . 1 ( m , 3h , ch 2 and h ), 3 . 84 ( m , 4h , 2xch 2 ), 4 . 8 - 5 . 1 ( ab q and s merged , ch 2 and oh ), 6 . 7 - 6 . 85 ( m , 2h , ar -- h ), 7 . 1 - 7 . 5 ( m , 7h , 6 ar -- h and 1 nh ), 7 . 77 ( s , 1h , het - h ), 7 . 88 ( s , 1h , het - h ). fab - ms : 473 . 3 ( mh + ), calcd . c 23 h 26 f 2 n 6 os 472 . 56 . the title compound was prepared similarly to example 8 starting from same piperazine derivative 2 and ethylthioisocyanate . the product was obtained as a colorless solid in 85 % yield . 1 h nmr ( cdcl 3 ) δ : 0 . 88 ( d , 3h , ch 3 ), 1 . 25 ( t , 3h , ch 3 ), 2 . 5 ( m , 2h , ch 2 ), 3 . 06 ( m , 3h , ch 2 and ch ), 3 . 6 - 4 . 0 ( q and m merged , 6h , 3xch 2 ), 4 . 8 - 5 . 0 ( ab q and s merged , 3h , ch 2 and oh ), 5 . 39 ( s , 1h , nh ), 6 . 7 - 6 . 9 ( m , 2h , ar -- h ), 7 . 4 - 7 . 5 ( m , 1h , ar -- h ), 7 . 78 ( s , 1h , het - h ), 7 . 89 ( s , 1h , het - h ). fab - ms : 425 . 1 ( mh + ), calcd . c 19 h 26 f 2 n 6 os 424 . 51 . to a mixture of compound 2 ( 674 mg , 2 mmol ) and triethylamine ( 0 . 55 ml , 4 mmol ) in tetrahydrofuran ( 10 ml ) was added dropwise 2 , 4 - difluorobezoyl chloride ( 440 mg , 2 . 5 mmol ) in 5 ml tetrahydrofuran at 0 ° c . the reaction mixture was stirred at 0 ° c . for 30 minutes and at room temperature for 18 h . the solvent was removed under reduced pressure , the residue was dissolved in dichloromethane ( 50 ml ). the organic phase was washed with brine , dried over sodium sulphate . the solvent was removed under reduced pressure and the resulting product was purified on a column of silica gel ( etoac / hexane , 9 : 1 ) to give the title compound as colorless prisms ( 448 mg , 47 %). 1 h nmr ( cdcl 3 ) δ : 0 . 88 ( d , j = 6 . 1 hz , 3h ), 2 . 04 - 2 . 59 ( m , 2h ); 2 . 99 - 3 . 09 ( m , 4h ); 3 . 35 ( s , 2h ); 3 . 72 - 4 . 10 ( m , 1h ) 4 . 91 ( s , 2h ); 5 . 01 ( s , 1h ); 6 . 65 - 7 . 00 ( m , 5h ); 7 . 34 - 7 . 48 ( m , 1h ); 7 . 77 ( s , 1h ); 7 . 9 ( s , 1h ). fab - ms : 478 . 3 ( mh + ), calcd . c 23 h 23 f 4 n 5 o 2 477 . 46 . the example 13 was prepared form the reaction of piperazino derivative 2 and 4 -( trifluoromethyl ) benzoyl chloride by following the similar procedure described for the example 12 . 1 h nmr ( cdcl 3 ) δ : 0 . 88 ( d , j = 6 . 5 hz , 3h ); 2 . 39 - 2 . 59 ( m , 2h ) 3 . 00 - 3 . 10 ( m , 4h ); 3 . 41 - 3 . 73 ( m , 4h ); 4 . 83 ( ab q , 2h ) 6 . 65 - 6 . 79 ( m , 2h ); 7 . 35 - 7 . 47 ( m , 1h ); 7 . 49 ( d , j = 8 . 0 hz , 2h ) 7 . 66 ( d , j = 8 . 0 hz , 2h ); 7 . 78 ( s , 1h ), 7 . 91 ( s , 1h ). fab - ms : 510 . 1 ( mh + ), calcd . c 24 h 24 f 5 n 5 o 2 509 . 48 . the example 14 was prepared form the reaction of piperazino derivative 2 and 4 - nitrobenzoyl chloride by following the similar procedure described for the example 12 . after column purification the product was obtained as brown prisms in 92 % yield . 1 h nmr ( cdcl 3 ) δ : 0 . 88 ( d , j = 6 . 5 hz , 3h ), 2 . 42 - 2 . 61 ( m , 2h ) 3 . 05 - 3 . 08 ( m , 4h ); 3 . 39 - 3 . 73 ( m , 3h ); 4 . 92 ( s , 3h ) 6 . 66 - 6 . 78 ( m , 2h ); 7 . 34 - 7 . 47 ( m , 1h ); 7 . 55 ( d , j = 8 . 6 hz , 2h ) 7 . 77 ( s , 1h ); 7 . 88 ( s , 1h ); 8 . 26 ( d , j = 8 . 6 hz , 2h ). fab - ms : 487 . 0 ( mh + ), c 23 h 24 f 2 n 6 o 4 486 . 42 . a solution of nitrocompound 14 ( 487 mg , 1 . 0 mmol ) in ethyl acetate ( 95 ml ) was hydrogenated over 10 % pd -- c ( 50 mg ) at 45 psi pressure and room temperature for 6 h . the catalyst was removed by filtration and the filtrate was concentrated to give the amino compound 15 as a colorless solid ( 330 mg , 72 %). 1 h nmr ( cdcl 3 ) δ : 0 . 89 ( d , j = 5 . 8 hz , 3h ); 2 . 42 - 2 . 47 ( m , 2h ) 2 . 88 - 3 . 06 ( m , 3h ); 3 . 63 ( br , 4h ); 3 . 09 ( br , 2h ) 4 . 82 ( t , j = 16 . 3 hz , 2h ); 5 . 02 ( br , 1h ); 6 . 61 ( d , j = 8 . 5 hz , 2h ) 6 . 73 - 6 . 79 ( m , 2h ); 7 . 22 ( d , j = 8 . 5 hz , 2h ); 7 . 30 - 7 . 48 ( m , 1h ) 7 . 77 ( s , 1h ); 7 . 92 ( s , 1h ). fab - ms : 457 . 1 ( mh + ), calcd . c 23 h 26 f 2 n 6 o 2 456 . 46 . to a mixture of piperazinyl compound 2 ( 146 mg , 0 . 43 mmol ) and triethylamine in dichloromethane ( 5 ml ) was added p - toluenesulphonyl chloride ( 51 mg , 0 . 45 mmol ) in dichloromethane ( 1 ml ) at 0 ° c . the reaction mixture was stirred at 0 ° c . for 15 minutes and 2 h at room temperature . then the reaction mixture was diluted with chloroform ( 15 ml ), washed with water , brine and dried over sodium sulphate . the solvent was removed under reduced pressure and the resulting product was purified on a column of silica gel ( chcl 3 / meoh ; 98 : 2 ) to give the title compound as a colorless solid ( 75 mg , 16 %). 1 h nmr ( cdcl 3 ) δ : 0 . 88 ( d , j = 6 . 9 hz , 3h ), 2 . 44 ( s , 3h ), 2 . 48 - 2 . 57 ( m , 2h ), 2 . 92 - 3 . 08 ( m , 7h ), 4 . 74 ( s , 2h ), 4 . 83 ( s , 1h ), 6 . 64 - 6 . 76 ( m , 2h ), 7 . 29 - 7 . 36 ( m , 3h ), 7 . 63 ( s , 1h ), 7 . 68 ( s , 1h ), 7 . 74 ( s , 1h ), 7 . 80 ( s , 1h ). fab - ms : 491 . 9 ( mh + ), calcd . c 23 h 27 f 2 n 5 o 3 s 491 . 55 . the epoxide iv ( 300 mg , 1 . 19 mmol ) and liclo 4 ( 235 mg , 1 . 43 mmol ) were dissolved in 12 ml dry acetonitrile and 1 - methanesulfonylpiperazine ( 190 mg , 1 . 79 mmol ) was added . the mixture was heated to reflux for 4 days , cooled and the solvent evaporated . the residue was dissolved in dichloromethane and then washed with water and brine . the solution was dried over na 2 so 4 and the solvent evaporated . the crude reaction products were eluted through a silica gel column using 3 % meoh / 97 % etoac as eluent to give the title compound ( 180 mg , 36 %) as a colorless solid . 1 h nmr ( cdcl 3 ) δ : 0 . 91 ( d , j = 6 . 4 hz , 3h ), 2 . 56 - 2 . 61 ( m , 2h ), 2 . 80 ( s , 3h ), 3 . 02 - 3 . 18 ( m , 3h ), 3 . 22 - 3 . 30 ( m , 4h ), 4 . 89 ( s , 2h ), 4 . 93 ( s , 1h ), 6 . 66 - 6 . 79 ( m , 2h ), 7 . 35 - 7 . 48 ( m , 1h ), 7 . 79 ( s , 1h ), 7 . 88 ( s , 1h ). fab - ms : 415 . 9 ( mh + ), c 17 h 23 f 2 n 5 o 3 s 415 . 45 the title compound was prepared from piperazinyl compound 2 and p - nitrobenzenesulphonyl chloride by following the similar procedure described for example 12 . the product was obtained as tan needles in 38 % yield after purification on a column of silica gel ( chcl 3 / meoh ; 96 : 4 ) followed by recrystalization in ether . 1 h nmr ( cdcl 3 ) δ : 0 . 87 ( d , j = 6 . 7 hz , 3h ), 2 . 51 - 2 . 66 ( m , 2h ), 2 . 96 - 3 . 20 ( m , 7h ), 4 . 74 ( s , 2h ), 4 . 81 ( s , 1h ), 6 . 62 - 6 . 76 ( m , 2h ), 7 . 29 - 7 . 41 ( m , 1h ), 7 . 72 ( s , 1h ), 7 . 77 ( s , 1h ), 7 . 94 - 7 . 98 ( m , 2h ), 8 . 39 - 8 . 43 ( m , 2h ). fab - ms : 523 . 2 ( mh + ), calcd . c 22 h 24 f 2 n 6 o 5 s 522 . 52 . a solution of nitrocompound 18 ( 230 mg , 0 . 44 mmol ) in ethanol ( 10 ml ) was hydrogenated over 10 % pd -- c ( 25 mg ) at 45 psi pressure and room temperature for 18 h . the catalyst was removed by filtration and the filtrate was concentrated and the resulting product was purified on a column of silica gel ( chcl 3 / meoh ; 57 : 43 ) to give the amino compound 19 as a colorless solid ( 165 mg , 76 %). 1 h nmr ( cdcl 3 ) δ : 0 . 88 ( 2 , j = 6 . 1 hz , 3h ), 2 . 48 - 2 . 58 ( m , 2h ), 2 . 96 - 3 . 09 ( m , 7h ), 4 . 14 ( br , 2h ), 4 . 75 ( s , 2h ), 4 . 86 ( s , 1h ), 6 . 63 - 6 . 77 ( m , 4h ), 7 . 31 - 7 . 43 ( m , 1h ), 7 . 52 - 7 . 57 ( m , 2h ), 7 . 74 ( s , 1h ), 7 . 83 ( s , 1h ). fab - ms : 493 . 5 ( mh + ), calcd . c 22 h 26 f 2 n 6 o 3 s 492 . 54 . to a cooled solution of 3 - amino - 1h - 1 , 2 , 4 - triazole ( 378 mg , 4 . 5 mmol ) in concentrated hydrochloric acid ( 1 ml ) was added sodium nitrite ( 310 mg , 4 . 5 mmol ) in portions . the resulting diazonium salt was transferred to a flask containing compound 2 ( 1 g , 3 . 0 mmol ) in 20 ml of 3 : 1 mixture of 10 % sodium hydroxide solution and tetrahydrofuran . the resulting reaction mixture was stirred at room temperature for 2 h and extracted with chloroform ( 3 × 25 ml ). the combined organic extract was washed with water , brine and dried over sodium sulphate . the solvent was removed under reduced pressure and the resulting product was purified on a column of silica gel to give the title compound as thick viscous gum ( 100 mg , 8 %). 1 h nmr ( cdcl 3 ) δ : 0 . 92 ( d , 3h , ch 3 ), 2 . 65 ( m , 2h , ch 2 ), 3 . 1 - 3 . 3 ( m , 3h , ch 2 and ch ), 4 . 0 ( m , 4h , 2xch 2 ), 4 . 95 ( m , 3h , ch 2 and oh ), 6 . 72 - 6 . 81 ( m , 2h , ar -- h ), 7 . 4 - 7 . 49 ( m , 1h , ar -- h ), 7 . 79 ( s , 1h , het - h ), 7 . 91 ( s , 1h , het - h ), 7 . 97 ( s , 1h , het - h ). fab - ms : 433 . 2 ( mh + ), calcd . c 18 h 22 f 2 n 10 o 432 . 43 . a mixture of 2 - bromothiazole ( 1 . 64 g , 10 mmol ), ethyl 1 - piperazinecarboxylate ( 1 . 896 , 12 mmol ) and sodium iodide ( 1 . 498 , 10 mmol ) in n , n - dimethylformamide ( 10 ml ) was heated at 120 ° c . for 18 h . after cooling , the solvent was removed under reduced pressure and the residue was treated with crushed ice . the desired product was precipitated as colorless solid , was isolated by filtration ( 2 . 2 g , 91 %). 1 h nmr ( cdcl 3 ) δ : 1 . 28 ( t , 3h , ch 3 ), 3 . 48 ( m , 4h , 2xch 2 ), 3 . 62 ( m , 4h , 2xch 2 ), 4 . 17 ( q , 2h , och 2 ), 6 . 60 ( d , 1h , het - h , j = 3 . 5 hz ), 7 . 20 ( d , 1h , het - h , j = 3 . 5 hz ) to a methanolic solution of ethyl 4 -( 2 - thiazolyl ) piperazine - 1 - carboxylate ( 2 g , 8 mmol ), 20 ml of 10 % sodium hydroxide solution was added . the resulting mixture was heated under reflux for 5 h . after cooling , the reaction mixture was concentrated under reduced pressure , the residue was diluted with water and extracted with chloroform ( 3 × 30 ml ). the combined extract was washed with water , brine , dried ( na 2 so 4 ) and concentrated to give the title compound as a thick viscous liquid ( 1 . 2 g , 86 %). 1 h nmr ( cdcl 3 ) δ : 1 . 68 ( br s , 1h , nh ), 2 . 98 ( m , 4h , 2xch 2 ), 3 . 46 ( m , 2xch 2 ), 6 . 56 ( d , 1h , het - h , j = 3 . 5 hz ), 7 . 2 ( d , 1h , het - h , j = 3 . 5 hz ). to a mixture of ( 2r , 3s )- 2 -( 2 , 4 - difluorophenyl )- 3 - methyl - 2 -( 1h - 1 , 2 , 4 - triazol - 1 - yl ) methyloxirane iv ( 502 mg , 2 mmol ) and lithium perchlorate ( 320 mg , 3 mmol ) in acetonitrile ( 10 ml ), 2 -( piperazin - 1 - yl ) thiazole ( x )( 507 mg , 3 mmol ) was added . the resulting mixture was heated under reflux for 48 h . the reaction mixture was cooled , concentrated under reduced pressure . the residue was disolved in chloroform , washed with water , brine , dried ( na 2 so 4 ) and concentrated . the resulting product was purified on a column of silica gel using ethyl acetate and hexane ( 4 : 1 ) as eluent to give the title compound as colorless solid ( 650 mg , 77 %). 1 h nmr ( cdcl 3 ) δ : 0 . 93 ( d , 3h , ch 3 ), 2 . 57 ( m , 2h , ch 2 ), 3 . 05 ( m , 3h , ch 2 and ch ) 3 . 51 ( m , 4h , 2xch 2 ), 4 . 92 ( ab q , 2h , ch 2 ), 5 . 05 ( s , 1h , oh ), 6 . 58 ( d , 1h , het - h , j = 3 . 5 hz ), 6 . 7 - 6 . 8 ( m , 2h , ar -- h ), 7 . 2 ( d , 1h , het - h , j = 3 . 5 hz ), 7 . 4 - 7 . 5 ( m , 1h , ar -- h ), 7 . 78 ( s , 1h , het - h ), 7 . 93 ( s , 1 - h , het - h ). fab - ms : 421 . 0 ( mh + ), calcd . c 19 h 22 f 2 n 6 os 420 . 482 . the title compound was prepared in 48 % yield from ( 2r , 3s )- 2 -( 2 , 4 - difluorophenyl )- 3 - methyl - 2 -( 1h - 1 , 2 , 4 - triazol - 1 - yl ) methyloxirane and 3 -( piperazin - 1 - yl )- 1h - 1 , 2 , 4 - triazole ( xi ) in the presence of lithium perchlorate following the similar procedure described for example 21 . 1 h nmr ( cdcl 3 ) δ : 0 . 91 ( d , 3h , ch 3 ), 2 . 48 - 2 . 60 ( m , 2h , ch 2 ), 2 . 90 - 3 . 03 ( m , 3h , ch 2 and ch ), 3 . 32 - 3 . 51 ( m , 4h , 2xch 2 ), 4 . 81 - 5 . 04 ( m , 2h , ch 2 ), 5 . 20 ( br , 2h ), 6 . 67 - 6 . 86 ( m , 2h , ar -- h ), 7 . 35 - 7 . 58 ( m , 1h , ar -- h ), 7 . 72 ( s , 1h , het - h ), 7 . 78 ( s , 1h , het - h ), 8 . 01 ( s , 1h , het - h ) fab - ms : 405 . 0 ( mh + ), calcd . c 18 h 22 f 2 n 8 o 404 . 36 . a mixture of compound 3 ( 140 mg , 0 . 39 mmol ), sodium azide ( 31 mg , 0 . 47 mmol ) and ammonium chloride ( 25 mg , 0 . 47 mmol ) in dmf ( 5 ml ) was heated at 90 ° c . for 48 h . solvent was removed under reduced pressure and the residue was extracted with ethyl acetate ( 3 × 10 ml ). combined organic extract was washed with water , brine and dried over sodium sulphate . the solvent was removed under reduced pressure and the resulting product was purified on a column of silica gel to give the title compound as a off - white solid ( 30 mg , 19 %). 1 h nmr ( cdcl 3 ) δ : 0 . 93 ( d , 3h , ch 3 ), 2 . 63 ( m , 2h , ch 2 ), 3 . 07 ( m , 3h , ch 2 and ch ), 3 . 56 ( m , 4h , 2xch 2 ), 4 . 93 ( ab q and s merged , 3h , ch 2 and oh ), 6 . 70 - 6 . 77 ( m , 2h , ar -- h ), 7 . 42 - 7 . 45 ( m , 1h , ar -- h ), 7 . 80 ( s , 1h , het - h ), 7 . 96 ( s , 1h , het - h ). fab - ms : 406 . 3 ( mh + ), calcd . c 17 h 21 f 2 n 9 o 405 . 42 the title compound was prepared from the epoxide iv and tetrazolylpiperazine xvi ( ar = 4 - tetrt - butylphenyl ) by following the similar procedure described for example 21 . after usual workup and column purification the title compound was obtained as a colorless solid in 36 % yield . 1 h nmr ( cdcl 3 ) δ : 0 . 94 ( d , 3h , ch 3 ), 1 . 30 ( s , 9h , 3xch 3 ), 2 . 47 - 2 . 59 ( m , 2h , ch 2 ), 2 . 91 - 3 . 01 ( m , 3h , ch 2 and ch ), 3 . 50 ( m , 4h , 2xch 2 ), 4 . 88 ( ab q , 2h , ch 2 ), 5 . 12 ( br s , 1h , oh ), 5 . 53 ( s , 2h , ch 2 ), 6 . 67 - 6 . 81 ( m , 2h , ar -- h ), 7 . 29 - 7 . 48 ( m , 5h , ar -- h ), 7 . 79 ( s , 1h , het - h ), 7 . 95 ( s , 1h , het - h ). fab - ms : 552 . 2 ( mh + ); calcd . c 28 h 3 f 2 n 9 o 551 . 61 . the title compound was prepared from the epoxide iv and tetrazolylpiperazine xvi ( ar = 4 -( trifluoromethyl ) phenyl ) by following the similar procedure described for example 21 . after usual workup and column purification the title compound was obtained as a colorless solid in 30 % yield . 1 h nmr ( cdcl 3 ) δ : 0 . 93 ( d , 3h , ch 3 ), 2 . 51 - 2 . 56 ( m , 2h , ch 2 ), 2 . 96 - 3 . 02 ( m , 3h , ch 2 and ch ), 3 . 49 ( m , 4h , 2xch 2 ), 4 . 90 ( ab q , 2h , ch 2 ), 5 . 07 ( s , 1h , oh ), 5 . 62 ( s , 2h , ch 2 ), 6 . 68 - 6 . 77 ( m , 2h , ar -- h ), 7 . 43 - 7 . 65 ( m , 5h , ar -- h ), 7 . 78 ( s , 1h , het - h ), 7 . 93 ( s , 1h , het - h ). fab - ms : 564 . 1 ( mh + ), calcd . c 25 h 26 f 5 n 9 o 563 . 54 . the title compound was prepared from the epoxide iv and triazolylpiperazine xii ( ar = 4 - tert - butylphenyl ) by following the similar procedure described for example 21 . after usual workup and column purification the title compound was obtained as a colorless solid in 45 % yield . 1 h nmr ( cdcl 3 ) δ : 0 . 93 ( d , 3h ), 1 . 30 ( s , 9h ), 2 . 49 - 2 . 59 ( m , 2h ), 2 . 95 - 3 . 07 ( m , 3h ), 3 . 12 - 3 . 14 ( m , 4h ), 4 . 78 - 4 . 95 ( m , 2h ), 5 . 04 ( s , 1h ), 5 . 15 ( s , 2h ), 6 . 66 - 6 . 80 ( m , 2h ), 7 . 12 ( d , 2h , j = 8 . 3 hz ), 7 . 34 ( d , 2h , j = 8 . 3 hz ), 7 . 35 - 7 . 49 ( m , 1h ), 7 . 69 ( s , 1h ), 7 . 76 ( s , 1h ), 7 . 92 ( s , 1h ). fab - ms : 551 . 4 ( mh + ), calcd . c 29 h 36 f 2 n 8 o 550 . 66 the title compound was prepared from the epoxide iv and triazolylpiperazine xiii ( ar = 4 - tert - butylphenyl ) by following the similar procedure described for example 21 . after usual workup and column purification the title compound was obtained as a colorless solid in 46 % yield . 1 h nmr ( cdcl 3 ): 6 : 0 . 94 ( d , 3h , ch 3 ), 1 . 30 ( s , 9h , 3xch 3 ), 2 . 45 - 2 . 55 ( m , 2h ), 2 . 83 - 3 . 01 ( m , 3h ), 3 . 42 - 3 . 48 ( m , 4h ), 4 . 79 - 4 . 97 ( m , 2h ), 5 . 11 ( s , 2h ), 5 . 22 ( s , 1h ), 6 . 67 - 6 . 81 ( m , 2h ), 7 . 16 ( d , 2h , j = 8 . 2 hz ), 7 . 36 ( d , 2h , j = 8 . 2 hz ), 7 . 41 - 7 . 53 ( m , 1h ), 7 . 66 ( s , 1h ), 7 . 78 ( s , 1h ), 7 . 97 ( s , 1h ). fab - ms : 551 . 3 ( mh + ), calcd . c 29 h 36 f 2 n 8 o 550 . 66 . the title compound was prepared from the epoxide iv and triazolylpiperazine xiii ( ar = 4 -( trifluoromethyl ) phenyl ) by following the similar procedure described for example 21 . after usual workup and column purification the title compound was obtained as a colorless solid in 18 % yield . 1 h nmr ( cdcl 3 ) δ : 0 . 96 ( d , 3h , ch 3 ), 2 . 49 - 2 . 54 ( m , 2h , ch 2 ), 2 . 88 - 2 . 99 ( m , 3h , ch 2 and ch ), 3 . 43 ( m , 4h , 2xch 2 ), 4 . 93 ( ab q , 2h , ch 2 ), 4 . 98 ( 2 s merged , 3h , ch 2 and oh ), 6 . 69 - 6 . 80 ( m , 2h , ar -- h ), 7 . 32 - 7 . 64 ( m , 5h , ar -- h ), 7 . 78 ( 2 s merged , 2h , het - h ), 7 . 98 ( s , 1h , het - h ). fab - ms : 562 . 9 ( mh + ), calcd . c 20 h 27 f 5 n 8 o 562 . 56 . the title compound was prepared by opening of the epoxide iv with 1 - phenylpiperazine in the presence of lithium perchlorate by following similar procedure described to example 21 . after column purification the compound was obtained as a colorless solid . 1h nmr ( cdcl 3 ) δ : 0 . 99 ( d , 3h , ch 3 ), 2 . 6 ( m , 2h , ch 2 ), 2 . 9 - 3 . 05 ( m , 3h , ch 2 and ch ), 4 . 89 ( ab q , 2h , ch 2 ), 5 . 23 ( s , 1h , oh ), 6 . 7 - 7 . 0 ( complex , 5h , ar -- h ), 7 . 2 - 7 . 3 ( m , 2h , ar -- h ), 7 . 5 ( m , 1h , ar -- h ), 7 . 79 ( s , 1h , ar -- h ), 7 . 79 ( s , 1h , het - h ), 7 . 97 ( s , 1h , het - h ). fab - ms : 414 . 1 ( mh + ), calcd . c 22 h 25 f 2 n 5 o 413 . 47 . the title compound was prepared similarly to example 21 using the oxirane iv ( 600 mg , 2 . 4 mmol ), 4 - nitrophenylpiperazine ( 660 mg , 3 . 2 mmol ) and lithium perchlorate ( 383 mg , 3 . 6 mmol ) as starting materials . after usual workup , the crude reaction product was purified on a column of silica gel ( etoac / hexane ) to give the desired compound as light yellow solid ( 920 mg , 84 %). 1 h nmr ( cdcl 3 ) δ : 0 . 94 ( d , 3h , ch 3 ), 2 . 58 - 2 . 64 ( m , 2h ,), 3 . 06 - 3 . 13 ( m , 3h ), 3 . 4 - 3 . 5 ( m , 4h ), 4 . 93 ( ab q , 2h , ch 2 ), 5 . 04 ( s , 1h , oh ), 6 . 7 - 6 . 85 ( m and d merged , 4h , ar -- h ), 7 . 38 - 7 . 51 ( m , 1h , ar -- h ), 7 . 79 ( s , 1h , het - h ), 7 . 91 ( s , 1h , het - h ), 8 . 13 ( d , 2h , ar -- h ). fab - ms : 459 . 2 ( mh + ), calcd . c 22 h 24 f 2 n 6 o 3 458 . 47 to a solution of nitrocompound 30 ( 600 mg , 1 . 3 mmol ) in 50 ml of ethyl acetate , 120 mg of 5 % platinum on charcoal was added . the reaction mixture was hydrogenated in parr hydrogenator at room temperature and 45 psi pressure for 18 h . the catalyst was removed by filtration and the filtrate was concentrated in vacuo . the pure amino compound 31 was obtained by dissolving the product in ethyl acetate and precipitating by addition of hexane ( 530 mg , 95 %). 1 h nmr ( cdcl 3 ) δ : 0 . 98 ( d , 3h , ch 3 ), 2 . 53 - 2 . 59 ( m , 2h , ch 2 ), 2 . 89 - 3 . 04 ( complex , 7h , 3xch 2 and ch ), 4 . 87 ( ab q , 2h , ch 2 ), 6 . 6 - 6 . 9 ( 2d and m merged , 6h , ar -- h ), 7 . 43 - 7 . 55 ( m , 1h , ar -- h ), 7 . 79 ( s , 1h , het - h ), 7 . 98 ( s , 1h , het - h ). fab - ms : 429 . 2 ( mh + ), calcd . c 22 h 26 f 2 n 6 o 428 . 487 . to a cooled ( 0 ° c .) mixture of amine 31 ( 300 mg , 0 . 7 mmol ) and triethylamine ( 0 . 4 ml ) in dichloromethane ( 30 ml ) was added ethyl chloroformate ( 160 mg , 1 . 5 mmol ) in dichloromethane ( 5 ml ). the reaction mixture was stirred at 0 ° c . for 2 h , then diluted with 30 ml of chloroform , washed with water , brine and dried over sodium sulphate . the solvent was removed under reduced pressure , the residue was purified on a column of silica gel ( hexane / etoac , 1 : 1 and 1 : 2 ) to give the title compound as amorphous solid ( 330 mg , 94 %). 1 h nmr ( cdcl 3 ) 6 : 0 . 99 ( d , 3h , ch 3 ), 1 . 29 ( t , 3h , ch 3 , j = 7 hz ), 2 . 58 ( m , 2h , ch 2 ), 2 . 95 ( m , 3h , ch 2 and ch ), 4 . 2 ( q , 2h , ch 2 , j = 7 hz ), 4 . 88 ( ab q , 2h , ch 2 ), 5 . 21 ( s , 1h , oh ), 6 . 44 ( s , 1h , nh ), 6 . 7 - 6 . 85 ( m , 2h , ar -- h ), 6 . 87 ( d , 2h , ar -- h , j = 8 . 9 hz ), 7 . 26 ( d , 2h , ar -- h , j = 8 . 9 hz ), 7 . 41 - 7 . 54 ( m , 1h , ar -- h ), 7 . 78 ( s , 1h , het - h ), 7 . 97 ( s , 1h , het - h ). fab - ms : 501 . 0 ( mh + ), calcd . c 25 h 30 f 2 n 6 o 3 500 . 55 . the title compound was prepared similarly to the above procedure using the amine 31 ( 428 mg , 1 mmol ) and phenyl chloroformate ( 235 mg , 1 . 5 mmol ) in the presence of triethylamine ( 0 . 4 ml ). after usual workup and purification on a silica gel column , the product was obtained as a colorless solid ( 475 mg , 89 %). 1 h nmr ( cdcl 3 ) δ : 0 . 98 ( d , 3h , ch 3 ), 2 . 58 ( m , 2h , ch 2 ), 2 . 98 ( m , 3h , ch 2 and ch ), 3 . 15 ( m , 4h , 2xch 2 ), 4 . 88 ( ab q , 2h , ch 2 ), 5 . 19 ( s , 1h , oh ), 6 . 7 - 7 . 0 ( d and m merged , 4h , ar -- h ), 7 . 2 - 7 . 6 ( complex , 8h , ar -- h ), 7 . 78 ( s , 1h , het - h ), 7 . 96 ( s , 1h , het - h ). fab - ms : 549 . 3 ( mh + ), calcd . c 29 h 30 f 2 n 6 o 3 548 . 594 . to a solution of compound 33 ( 400 mg , 0 . 73 mmol ) in dimethoxyethane ( 10 ml ) was added hydrazine ( 1 ml ) dropwise at room temperature and stirred for 4 h . the reaction mixture was concentrated under reduced pressure and the residue was treated with crushed ice . the precipitated product was isolated by filtration and washed with water and hexane to give the title compound as a colorless solid ( 300 mg , 85 %). 1 h nmr ( cdcl 3 ) δ : 0 . 99 ( d , 3h , ch 3 ), 2 . 54 - 2 . 60 ( m , 2h , ch 2 ), 2 . 90 - 3 . 0 ( m , 3h , ch 2 and ch ), 3 . 10 ( m , 4h , 2xch 2 ), 3 . 8 ( br s , 2h , nh2 ), 4 . 88 ( ab q , 2h , ch 2 ), 5 . 7 ( br s , 1h , oh ), 6 . 09 s , 1h , nh ), 6 . 7 - 6 . 9 ( d and m merged , 4h , ar -- h ), 7 . 3 - 7 . 6 ( d and m merged , 3h , ar -- h ), 7 . 8 ( s , 1h , het - h ), 7 . 93 ( br s , 1h , nh ), 8 . 0 ( s , 1h , het - h ). fab - ms : 487 . 0 ( mh + ), calcd . c 23 h 28 f 2 n 8 o 2 486 . 527 . to a mixture of semicarbazide 34 ( 486 mg , 1 mmol ) and formamidine acetate ( 416 mg , 4 mmol ) in methoxyethanol ( 5 ml ), triethylamine ( 0 . 8 ml ) was added . the reaction mixture was heated at 110 ° c . for 18 h . solvent was removed under reduced pressure and the residue was treated with crushed ice , extracted with ethyl acetate ( 3 × 30 ml ). the combined extract was successively washed with water and brine and dried over sodium sulphate . the solvent was removed under reduced pressure , the crude product was purified on a column of silica gel ( etoac / meoh , 9 : 1 ) to give the triazolone 35 as a crystaline solid ( 320 mg , 65 %). 1 h nmr ( cdcl 3 ) δ : 0 . 98 ( d , 3h , ch 3 , j = 6 . 4 hz ), 2 . 57 - 2 . 63 ( m , 2h , ch 2 ), 2 . 95 - 3 . 1 ( m , 3h , ch 2 and ch ), 4 . 9 ( ab q , 2h , ch 2 ), 5 . 14 ( s , 1h , oh ), 6 . 7 - 6 . 82 ( m , 2h , ar -- h ), 6 . 98 ( d , 2h , ar -- h , j = 8 . 9 hz ), 7 . 37 ( d , 2h , j = 8 . 9 , ar -- h ), 7 . 4 - 7 . 5 ( m , 1h , ar -- h ), 7 . 62 ( s , 1h , het - h ), 7 . 79 ( s , 1h , het - h ), 7 . 95 ( s , 1h , het - h ). fab - ms : 497 . 0 ( mh + ), calcd . c 24 h 26 f 2 n 8 o 2 496 . 522 to a mixture of triazolone 35 ( 248 mg , 0 . 5 mmol ) and cesium carbonate ( 326 mg , 1 mmol ) in dmf , 3 - bromopentane ( 226 mg , 1 . 5 mmol ) was added . the reaction mixture was heated at 80 ° c . for 18 h and concentrated in vacuo . the residue was treated with crushed ice , extracted with ethyl acetate ( 3 × 30 ml ). the combined extract was washed with brine , dried ( na 2 so 4 ) and the solvent was removed under rduced pressure . the resulting crude product was purified on a column of silica gel ( hexane / etoac ) to give the title compound 36 as a crystaline solid ( 240 mg , 85 %). the title compound was also prepared in an alternate method in a convergent approach according to scheme - 1 . thus a mixture of ( 2r , 3s )- 2 -( 2 , 4 - difluorophenyl )- 3 - methyl - 2 -( 1h - 1 , 2 , 4 - triazol - 1 - yl ) methyloxirane iv , piperazino compound xxiii ( r = 3 - pentyl ) and lithium perchlorate were heated in acetonitrile for 48 h . after usual workup and chromatographic purification , the title compound was obtained in 75 % yield . 1 h nmr ( cdcl 3 ) δ : 0 . 88 ( t , 6h , 2xch 3 ), 0 . 98 ( d , 3h , ch 3 ), 1 . 65 - 1 . 8 ( m , 4h , 2xch 2 ), 2 . 60 ( m , 2h , ch 2 ), 3 . 1 ( m , 3h , ch 2 and ch ), 3 . 2 ( m , 4h , 2xch 2 ), 4 . 12 ( m , 1h , ch ), 4 . 9 ( ab q , 2h , ch 2 ), 5 . 18 ( s , 1h , oh ), 6 . 7 - 6 . 8 ( m , 2h , ar -- h ), 6 . 97 ( d , 2h , ar -- h , j = 9 hz ), 7 . 4 - 7 . 6 ( d and m merged , 3h , ar -- h ), 7 . 64 ( s , 1h , het - h ), 7 . 79 ( s , 1h , het - h ), 7 . 96 ( s , 1h , het - h ). fab - ms : 567 . 3 ( mh + ), calcd . c 29 h 36 f 2 n 8 o 2 566 . 657 . the title compound was prepared from ( 2s , 3s )- 2 -( 2 , 4 - difluorophenyl )- 3 - methyl - 2 -( 1h - 1 , 2 , 4 - triazol - 1 - yl ) methyloxirane and piperazino compound xxiii ( r = 3 - pentyl ) by following the similar procedure described for the example 36 . 1 h nmr ( cdcl 3 ) δ : 0 . 88 ( t , 6h , 2xch 3 ), 1 . 25 ( d , 3h , ch 3 ), 1 . 65 - 1 . 84 ( m , 4h , 2xch 2 ), 2 . 46 ( m , 2h , ch 2 ), 2 . 75 ( m , 2h , ch 2 ), 2 . 93 ( m , 4h , 2xch 2 ), 3 . 19 ( q , 1h , ch ), 4 . 05 ( m , 1h , ch ), 4 . 44 ( d , 1h , j = 14 hz ), 4 . 95 ( d , 1h , j = 14 hz ), 4 . 98 ( s , 1h , oh ), 6 . 64 - 6 . 77 ( m , 2h , ar -- h ), 6 . 74 ( d , 2h , ar -- h ), 7 . 29 - 7 . 43 ( m , 3h ar -- h ), 7 . 59 ( s , 1h , het - h ), 7 . 77 ( s , 1h , het - h ), 7 . 93 ( s , 1h , het - h ). fab - ms : 567 . 2 ( mh + ), calcd . c 29 h 36 f 2 n 8 o 2 566 . 657 . the title compound was prepared from ( 2s , 3r )- 2 -( 2 , 4 - difluorophenyl )- 3 - methyl - 2 -( 1h - 1 , 2 , 4 - triazol - 1 - yl ) methyloxirane and piperazino compound xxiii ( r = 3 - pentyl ) by following the similar procedure described for the example 36 . 1 h nmr ( cdcl 3 ) δ : 0 . 88 ( t , 6h , 2xch 3 ), 0 . 97 ( d , 3h , ch 3 ), 1 . 70 - 1 . 84 ( m , 4h , 2xch 2 ), 2 . 63 ( m , 2h , ch 2 ), 3 . 01 ( m , 3h , ch 2 and ch ), 3 . 22 ( m , 4h , 2xch 2 ), 4 . 12 ( m , 1h , ch ), 4 . 90 ( ab q , 2h , ch 2 ), 5 . 14 ( s , 1h , oh ), 6 . 69 - 6 . 82 ( m , 2h , ar -- h ), 6 . 96 ( d , 2h , ar -- h ), 7 . 40 - 7 . 49 ( m and d merged , 3h , ar -- h ), 7 . 63 ( s , 1h , het - h ), 7 . 79 ( s , 1h , het - h ), 7 . 95 ( s , 1h , het - h ). fab - ms : 567 . 4 ( mh + ), calcd . c 29 h 36 f 2 n 8 o 2 566 . 657 . the title compound was prepared from ( 2r , 3r )- 2 -( 2 , 4 - difluorophenyl )- 3 - methyl - 2 -( 1h - 1 , 2 , 4 - triazol - 1 - yl ) methyloxirane and piperazino compound xxiii ( r = 3 - pentyl ) by following the similar procedure described for the example 36 . 1 h nmr ( cdcl 3 ) δ : 0 . 87 ( t , 6h , 2xch 3 ), 1 . 25 ( d , 3h , j = 7 hz ), 1 . 69 - 1 . 87 ( m , 4h , 2xch 2 ), 2 . 46 ( m , 2h , ch 2 ), 2 . 75 - 2 . 95 ( m , 6h , 3xch 2 ), 3 . 19 ( q , 1h , j = 7 hz ), 4 . 07 ( m , 1h , ch ), 4 . 45 ( d , 1h , j = 15 hz ), 4 . 94 ( d , 1h , j = 15 hz ), 5 . 03 ( s , 1h , oh ), 6 . 66 - 6 . 76 ( m , 2h , ar -- h ), 6 . 87 ( d , 2h , ar -- h ), 7 . 34 - 7 . 39 ( d and m merged , 3h , ar -- h ), 7 . 60 ( s , 1h , het - h ), 7 . 77 ( s , 1h , het - h ), 7 . 93 ( s , 1h , het - h ). fab - ms : 567 . 1 ( mh + ), calcd . c 29 h 36 f 2 n 8 o 2 566 . 657 . the example 40 was prepared similarly to the above procedure by alkylation of triazolone 35 with 2 - bromobutane in the presence of cesium carbonate . after column chromatography the product was obtained as a colorless solid . 1 h nmr ( cdcl 3 ) δ : 0 . 90 ( t , 3h , ch 3 ), 0 . 98 ( d , 3h , ch 3 ), 1 . 6 - 1 . 9 ( m , 2h , ch 2 ), 2 . 60 ( m , 2h , ch 2 ), 3 . 0 ( m , 3h , ch 2 and ch ), 3 . 22 ( m , 4h , 2xch 2 ), 4 . 29 ( m , 1h , ch ), 4 . 9 ( ab q , 2h , ch 2 ), 5 . 14 ( s , 1h , oh ), 6 . 65 - 6 . 85 ( m , 2h , ar -- h ), 6 . 96 ( d , 2h , ar -- h , j = 8 . 9 hz ), 7 . 5 ( m , 1h , ar -- h ), 7 . 61 ( s , 1h , het - h ), 7 . 79 ( s , 1h , het - h ), 7 . 95 ( s , 1h , het - h ). fab - ms : 553 . 1 ( mh + ), calcd . c 28 h 34 f 2 n 8 o 2 552 . 573 . the title compound 41 was prepared by alkylation of triazolone 35 with 2 - bromopropane in the presence of cesium carbonate following the procedure similar to the above described for example 36 . 1 h nmr ( cdcl 3 ) δ : 0 . 97 ( d , 3h , ch 3 ), 1 . 40 ( d , 6h , 2xch 3 ), 2 . 60 ( m , 2h , ch 2 ), 3 . 0 ( m , 3h , ch 2 and ch ), 3 . 22 ( m , 4h , 2xch 2 ), 4 . 55 ( m , 1h , ch ), 4 . 9 ( ab q , 2h , ch 2 ), 5 . 15 ( s , 1h , oh ), 6 . 7 - 6 . 85 ( m , 2h , ar -- h ), 6 . 96 ( d , 2h , ar -- h , j = 9 hz ), 7 . 38 ( d , 2h , ar -- h , j = 9 hz ), 7 . 5 ( m , 1h , ar -- h ), 7 . 59 ( s , 1h , het - h ), 7 . 79 ( s , 1h , het - h ), 7 . 95 ( s , 1h , het - h ). fab - ms : 539 ( mh + ), calcd . c 27 h 32 f 2 n 8 o 2 538 . 6 . to a mixture of triazolone 35 ( 248 mg , 0 . 5 mmol ) and potassium carbonate ( 138 mg , 1 mmol ) in dmf ( 6 ml ), 1 , 2 - epoxypropane ( 870 mg , 15 mmol ) was added . the reaction mixture was heated at 60 ° c . for 18 h and concentrated in vacuo . the residue was treated with crushed ice , extracted with ethyl acetate ( 3 × 30 ml ). the combined extract was washed with brine , dried ( na 2 so 4 ) and the solvent was removed under reduced pressure . the resulting crude product was purified on a column of silica gel ( etoac / meoh , 9 : 1 ) to give the hydoxypropyltriazolone 42 as a colorless solid ( 200 mg , 72 %). 1 h nmr ( cdcl 3 ) δ : 0 . 97 ( d , 3h , ch 3 ), 1 . 28 ( d , 3h , ch 3 ), 2 . 60 ( m , 2h , ch 2 ), 2 . 9 - 3 . 1 ( m and q merged , 3h , ch 2 and ch ), 3 . 23 ( m , 4h , 2xch 2 ), 3 . 7 - 4 . 0 ( m , 2h , ch 2 ), 4 . 8 - 5 . 0 ( ab q , 2h , ch 2 ), 5 . 12 ( s , 1h , oh ), 6 . 65 - 6 . 85 ( m , 2h , ar -- h ), 6 . 96 ( d , 2h , ar -- h , j = 9 hz ), 7 . 37 ( d , 2h , ar -- h , j = 9 hz ), 7 . 5 ( m , 1h , ar -- h ), 7 . 63 ( s , 1h , het - h ), 7 . 78 ( s , 1h , het - h ), 7 . 94 ( s , 1h , het - h ). fab - ms : 555 . 3 ( mh + ), calcd . c 27 h 32 f 2 n 8 o 3 554 . 60 to a solution of 1 -( nitrophenyl ) piperazine ( 20 . 7 , 0 . 1 mol ) and triethylamine ( 21 ml ) in dichloromethane ( 250 ml ) at 0 - 5 ° c . was added dropwise a solution of di - tert - butyldicarbonate in dichloromethane ( 50 ml ). the resulting mixture was stirred at 0 - 5 ° c . for 2 h and at room temperature for 18 h . then the reaction mixture was diluted with 100 ml of chloroform , washed with water , brine and dried over sodium sulphate . the solvent was removed under reduced pressure and the residue was triturated with hexane and hexane / ethyl acetate mixture to give the title compound as a yellow solid ( 29 g , 94 %). 1 h nmr ( cdcl 3 ) δ : 1 . 5 ( s , 9h , 3xch 3 ), 3 . 43 ( t , 4h , 2xch 2 ), 3 . 6 ( t , 4h , 2xch 2 ), 6 . 8 ( d , 2h , ar -- h , j = 9 hz ), 8 . 15 ( d , 2h , ar -- h , j = 9 hz ). a solution of butyl 4 -( 4 - nitrophenyl ) piperazine ( 60 g , 0 . 195 mol ) in ethyl acetate ( 800 ml ) was hydrogenated in the presence of 10 % palldium on charcoal ( 6 . 0 ) at room temperature and 45 psi pressure in the parr hydrogenator for 18 h . the catalyst was removed by filtration and the filtrate was concentrated in vacuo to give the title compound as a offwhite solid ( 50 g , 93 %). 1 h nmr ( cdcl 3 ) δ : 1 . 49 ( s , 9h , 3xch 3 ), 3 . 0 ( t , 4h , 2xch 2 ), 3 . 4 ( br s , 2h , nh 2 ), 3 . 5 ( t , 4h , 2xch 2 ), 6 . 65 ( d , 2h , ar -- h ), 6 . 85 ( d , 2h , ar -- h ). to a solution of tert - butyl 4 -( 4 - aminophenyl ) piperazine - 1 - carboxylate ( 50 g , 0 . 18 mol ) and triethylamine ( 39 ml , 0 . 27 mol ) in dichloromethane ( 400 ml ) was added dropwise a solution of phenyl chloroformate ( 36 . 65 g , 0 . 23 mol ) in dichloromethane ( 100 ml ) at 0 ° c . the resulting reaction mixture was stirred for 2 h at 0 ° c . and additional 3 h at room temperature . then diluted with chloroform ( 100 ml ), washed with water , brine and dried over sodium sulphate . the solvent was removed under reduced pressure , the crude product was purified on a column of silica gel ( hexane / etoac , 1 : 1 ) to give the tiltle compound as colorless solid ( 60 g , 84 %). 1 h nmr ( cdcl 3 ) δ : 1 . 48 ( s , 9h , 3xch 3 ), 3 . 0 - 3 . 2 ( m , 4h , 2xch 2 ), 3 . 6 ( m , 4h , 2xch 2 ), 6 . 8 ( brs , 1h , nh ), 6 . 92 ( d , 2h , ar -- h ), 7 . 1 - 7 . 5 ( complex , 7h , ar -- h ). to a solution of tert - butyl 4 -( phenoxycarbonylaminophenyl ) piperazine - 1 - carboxylate ( 36 g , 90 mmol ) in dimethoxyethane ( 300 ml ), anhydrous hrazine ( 40 g , 1 . 25 mol ) was added . the resulting reaction mixture was stirred at room temperature for 3 - 5 h . solvent was removed under reduced pressure and the residue was treated with crushed ice and left overnight at room temperature . the precipitated solid was collected , washed with water and hexane to give the title compound as a offwhite solid ( 25 g , 82 %). 1 h nmr ( cdcl 3 ) δ : 1 . 48 ( s , 9h , 3xch 3 ), 3 . 06 ( t , 4h , 2xch 2 ), 3 . 58 ( t , 4h , 2xch 2 ), 3 . 82 ( s , 2h , nh2 ), 5 . 98 ( s , 1h , nh ), 6 . 89 ( d , 2h , ar -- h , j = 8 . 9 hz ), 7 . 36 ( d , 2h , ar -- h , j = 8 . 9 hz ), 7 . 95 ( s , 1h , nh ). a mixture of 4 -[ 4 -( 4 - t - boc - piperazin - 1 - yl ) phenylsemicarbazide ( 25 g , 75 mmol ), formamidine acetate ( 31 , 2 g , 300 mmol ) and triethylamine ( 50 . 5 ml , 360 mmol ) in methoxyethanol ( 250 ml ) was heated at 110 ° c . for 18 h . the solvent was removed under reduced pressure , the residue was treated with crushed ice and extracted with ethyl acetate ( 3 × 250 ml ). combined extract was successively washed with water and brine and dried over sodium sulphate . the solvent was removed under reduced pressure and the product was purified on a column of silica gel to give the title compound as a colorless solid ( 16 . 7 g , 65 %). 1 h nmr ( cdcl 3 ) δ : 1 . 48 ( s , ( h , 9h , 3xch 3 ), 3 . 16 ( t , 4h , 2xch 2 ), 3 . 59 ( t , 4h , 2xch 2 ), 6 . 98 ( d , ar -- h , j = 9 hz ), 7 . 38 ( d , 2h , ar -- h ), 7 . 62 ( s , 1h , het - h ), 9 . 7 ( brs , 1h , nh ). a mixture of 4 [ 4 -( 4 - t - boc - piperazin - 1 - yl ) phenyl - 2h - 1 , 2 , 4 - triazol - 3 - one xxi ( 3 . 45 g , 10 mmol ), 3 - bromopentane ( 4 . 53 g ) and potassium carbonate ( 2 . 76 g , 20 mmol ) in dmf ( 30 ml ) was heated at 80 ° c . for 18 h . the solvent was removed under reduced pressure , the residue was diluted with water , extracted with ethyl acetate ( 3 × 50 ml ). the combined extract was washed with water , brine , dried ( na 2 so 4 ) and concentrated in vacuo . the resulting product was purified on a column of silica gel ( 2 . 9 g , 70 %) to give the title compound as a colorless solid . 1 h nmr ( cdcl 3 ) δ : 0 . 88 ( t , 6h , 2xch 3 ), 1 . 48 ( s , 9h , 3xch 3 ), 1 . 7 - 1 . 9 ( m , 4h , 2xch 2 ), 3 . 15 ( t , 4h , 2xch 2 ), 3 . 59 ( t , 4h , 2xch 2 ), 4 . 05 ( m , 1h , ch ), 6 . 98 ( d , 2h , ar -- h , j = 9 hz ), 7 . 44 ( d , 2h , ar -- h , j = 9 hz ), 7 . 63 ( s , 1h , het - h ). to a solution of 2 -( 3 - pentyl )- 4 -[ 4 -( 4 - t - boc - piperazin - 1 - yl ) phenyl - 1h - 1 , 2 , 4 - triazol - 3 - one ( 2 . 5 g , 6 mmol ) in ethyl acetate ( 30 ml ), 30 ml of 10 % hydrochloric acid was added . the resulting heterogenious mixture was stirred at room temperature for 5 h . solvent was removed under reduced pressure , the residue was diluted with water , basified with potassium carbonate and extracted with chloroform ( 3 × 50 ml ). the combined extract was washed with water , brine , dried ( na 2 so 4 ) and concentrated to give the title compound as colorless solid ( 1 . 8 g , 95 %). 1 h nmr ( cdcl 3 ) δ : 0 . 88 ( t , 6h , 2xch 3 ), 1 . 7 - 1 . 9 ( m , 4h , 2xch 2 ), 3 . 07 ( m , 4h , 2xch 2 ), 3 . 18 ( m , 4h , 2xch 2 ), 4 . 05 ( m , 1h , ch ), 6 . 95 ( d , 2h , ar -- h ), 7 . 42 ( d , 2h , ar -- h ), 7 . 63 ( s , 1h , het - h ). the title compound was obtained by alkylation of triazolone xxi with 2 - bromobutane in the presence of potassium carbonate . 1 h nmr ( cdcl 3 ) δ : 0 . 90 ( t , 3h , ch 3 ), 1 . 39 ( d , 3h , ch 3 ), 1 . 48 ( s , 9h , 3xch 3 ), 1 . 8 ( m , 2h , ch 2 ), 3 . 15 ( t , 4h , 2xch 2 ), 3 . 59 ( t , 4h , 2xch 2 ), 4 . 3 ( m , 1h , ch ), 6 . 97 ( d , 2h , ar -- h , j = 8 . 9 hz ), 7 . 42 ( d , 2h , ar -- h , j = 8 . 9 hz ), 7 . 61 ( s , 1h , het - h ). the title compound was obtained by removal of t - boc group of 2 -( 2 - butyl )- 4 [ 4 -( 4 - t - boc - piperazin - 1 - yl ) phenyl ]- 2h - 1 , 2 , 4 - triazol - 3 - one with 3m hydrochloric acid . 1 h nmr ( cdcl 3 ) δ : 0 . 90 ( t , 3h , ch 3 ), 1 . 39 ( d , 3h , ch 3 ), 3 . 04 ( m , 4h , 2xch 2 ), 3 . 17 ( m , 4h , 2xch 2 ), 4 . 29 ( m , 1h , ch ), 6 . 98 ( d , 2h , ar -- h , j = 8 . 9 hz ), 7 . 4 ( d , 2h , ar -- h , j = 8 . 9 hz ), 7 . 61 ( s , 1h , het - h ). the title compound was obtained by alkylation of triazolone xxi with 2 - bromopropane in the presence of potassium carbonate . m . p : 166 - 167 ° c . 1 h nmr ( cdcl 3 ) δ : 1 . 41 ( d , 6h , 2xch 3 ), 1 . 49 ( s , 9h , 3xch 3 ), 3 . 16 ( t , 4h , 2xch 2 ), 3 . 59 ( 2xch 2 ), 4 . 55 ( m , 1h , ch ), 6 . 97 ( d , 2h , ar -- h , j = 8 . 9 hz ), 7 . 40 ( d , 2h , ar -- h , j = 8 . 9 hz ), 7 . 59 ( s , 1h , het - h ). 4 -[ 4 -( piperazin - 1 - yl ) phenyl ] 2 -( 2 - propyl )- 2h - 1 , 2 , 4 - triazol - 3 - one ( xxiii ; x ═ h , r = 2 - propyl ): the title compound was obtained by removal of t - boc group of 4 -[ 4 -( 4 - t - boc - piperazin - 1 - yl ) phenyl ]- 2 -( 2 - propyl )- 2h - 1 , 2 , 4 - triazol - 3 - one with 3m hydrochloric acid . 1 h nmr ( cdcl 3 ) δ : 1 . 41 ( d , 6h , 2xch 3 ), 3 . 04 ( m , 4h , 2xch 2 ), 3 . 17 ( m , 4h , 2xch 2 ), 4 . 55 ( m , 1h , ch ), 6 . 97 ( d , 2h , ar -- h , j = 9 hz ), 7 . 38 ( d , 2h , ar -- h , j = 9 hz ), 7 . 59 ( s , 1h , het - h ). the title compound was obtained by alkylation of triazolone xxi with 1 , 2 - epoxypropane in the presence of potassium carbonate . 1 h nmr ( cdcl 3 ) δ : 1 . 28 ( d , 3h , ch 3 ), 1 . 48 ( s , 9h , 3xch 3 ), 3 . 17 ( t , 4h , 2xch 2 ), 3 . 4 ( brs , 1h , oh ), 3 . 59 ( t , 4h , 2xch 2 ), 3 . 70 ( dd , 1h ), 3 . 96 ( dd , 1h ), 4 . 2 ( m , 1h , ch ), 6 . 98 ( d , 2h , ar -- h , j = 8 . 9 hz ), 7 . 39 ( d , 2h , ar -- h , j = 8 . 9 hz ), 7 . 63 ( s , 1h , het - h ). the title compound was obtained by removal of t - boc group of 2 -( 2 - hydroxypropyl )- 4 -[ 4 -( 4 - t - boc - piperazin - 1 - yl ) phenyl ]- 2h - 1 , 2 , 4 - triazol - 3 - one with 3m hydrochloric acid . 1 h nmr ( cdcl 3 ) δ : 1 . 28 ( d , 3h , ch 3 ), 3 . 0 ( m , 4h , 2xch 2 ), 3 . 2 ( m , 4h , 2xch 2 ), 3 . 8 - 4 . 0 ( m , 2h , ch 2 ), 4 . 2 ( m , 1h , ch ), 6 . 98 ( d , 2h , ar -- h , j = 9 hz ), 7 . 3 ( d , 2h , ar -- h , j = 9 hz ), 7 . 62 ( s , 1h , het - h ) the title compound was prepared by alkylation of triazolone xxi ( x ═ h ) with 4 -( trifluoromethyl ) benzyl bromide in the presence of potassium carbonate . after usual workup and purification on a column of silica gel , the title compound was obtained in 95 % yield as a colorless solid . 1 h nmr ( cdcl 3 ) δ : 1 . 49 ( s , 9h , 3xch 3 ); 3 . 16 ( t , 4h , 2x 2 ); 3 . 59 ( t , 4h , 2x ch 2 ); 5 . 06 ( s , 2h , ch 2 ); 6 . 98 ( d , 2h , j = 8 . 9 hz , ar -- h ), 7 . 39 ( d , 2h , j = 8 . 9 hz , ar -- h ); 7 . 5 - 7 . 60 ( m , 6h , ar -- h ); 7 . 64 ( s , 1h , het - h ). the title compound was obtained by removal of t - boc group of 4 -[ 4 -( 4 - t - boc - piperazin - 1 - yl ) phenyl ]- 2 -[( 4 - trifluoromethyl ) benzyl ]- 2h - 1 , 2 , 4 - triazol - 3 - one with 3m hydrochloric acid . after usual workup the product was obtained as a colorless solid in 95 % yield . 1 h nmr ( dmso - d 6 ) δ : 2 . 81 - 2 . 84 ( m , 4h , 2xch 2 ); 3 . 04 - 3 . 07 ( m , 4h , 2x ch 2 ); 5 . 05 ( s , 2h , ch 2 ); 7 . 0 ( d , 2h , j = 9 hz , ar -- h ); 7 . 43 - 7 . 53 ( m , 4h , ar -- h ); 7 . 73 ( d , 2h , j = 8 hz , ar -- h ); 8 . 38 ( s , 1h , het - h ). the title compound was prepared from ( 2r , 3s )- 2 -( 2 , 4 - difluorophenyl )- 3 - methyl - 2 -( 1h - 1 , 2 , 4 - triazol - 1 - yl ) methyloxirane iv and piperazino compound xxiii ( r = 4 - trifluoromethylbenzyl ; x ═ h ) by following the similar procedure described for the example 36 . 1 h nmr ( cdcl 3 ) δ : 0 . 98 ( d , 3h , j = 5 . 5 hz , ch 3 ), 2 . 57 - 2 . 63 ( m , 2h , ch 2 ); 3 . 0 - 3 . 05 ( m , 3h ); 3 . 08 - 3 . 23 ( m , 4h , 2xch 2 ); 4 . 814 . 99 ( q , 2h , ch 2 ); 5 . 07 ( s , 2h , ch 2 ); 5 . 15 ( s , 1h ); 6 . 68 - 7 . 64 ( m , 12h ); 7 . 79 ( s , 1h , het - h ); 7 . 95 ( s , 1h , het - h ). fab - ms : 657 . 3 ( mh + ); calcd . c 32 h 31 o 2 f 5 n 8 656 . 64 . the title compound was obtained by alkylation of triazolone xxi ( x ═ h ) with 2 , 2 , 3 , 3 - tetrafluropropyl methanesulphonate in the presence of potassium carbonate . the product was obtained as light yellow solid in quantitative yield . 1 h nmr ( cdcl 3 ) δ : 1 . 48 ( s , 9h , 3xch 3 ); 3 . 18 ( t , 4h , 2xch 2 ); 3 . 59 ( t , 4h , 2xch 2 ); 4 . 34 - 4 . 48 ( m , 2h ) 5 . 71 - 6 . 28 ( m , 1h , chf 2 ); 6 . 98 ( d , 2h , ar -- h ) 7 . 39 ( d , 2h , ar -- h ); 7 . 69 ( s , 1h , het - h ). the title compound was obtained by the deprotection of the boc group of the above compound with 3n hydrochloric acid . the product was obtianed as light yellow solid in quantitative yield . this was used in the following step without further purification . 1 h nmr ( cdcl 3 ) o : 3 . 01 - 3 . 21 ( m , 8h ); 4 . 334 . 62 ( m , 3h , ch 2 and n -- h ); 5 . 67 - 6 . 29 ( m , 1h , chf 2 ); 6 . 97 ( d , 2h , ar -- h ); 7 . 37 ( d , 2h , ar -- h ); 7 . 70 ( s , 1h , het - h ). the title compound was prepared from ( 2r , 3s )- 2 -( 2 , 4 - difluorophenyl )- 3 - methyl - 2 -( 1h - 1 , 2 , 4 - triazol - 1 - yl ) methyloxirane iv and piperazino compound xxiii ( r = 2 , 2 , 3 , 3 ,- tetrafluoropropyl ; x ═ h ) by following the similar procedure described for the example 36 . 1 h nmr ( cdcl 3 ) δ : 0 . 97 ( d , 3h , j = 5 . 4 hz , ch 3 ); 2 . 57 - 2 . 65 ( m , 2h , ch 2 ); 3 . 00 - 3 . 23 ( m , 7h ); 4 . 35 - 4 . 48 ( m , 2h , ch 2 ); 4 . 82 - 5 . 00 ( m , 2h , ch 2 ); 5 . 13 ( s , 1h ); 5 . 71 - 6 . 28 ( m , 1h , -- chf 2 ); 6 . 69 - 6 . 83 ( m , 2h , ar -- h ); 6 . 96 ( d , 2h , j = 9 hz ; ar -- h ); 7 . 35 - 7 . 53 ( m , 3h , ar -- h ); 7 . 68 ( s , 1h , het - h ); 7 . 79 ( s , 1h , het - h ); 7 . 95 ( s , 1h , het - h ). fab - ms : 611 , 2 ( mh + ), calcd . c 27 h 28 o 2 f 6 n 8 610 . 56 . the title compound was prepared from the reaction of triazolone xxi ( x ═ h ) with 2 , 2 , 2 - trifluroethyl bromide in a sealed vessel in the presence of potassium carbonate . after usual workup and purification on a column of silica gel , the alkylated compound was obtained as a colorless solid in 21 % yield . 1 h nmr ( cdcl 3 ) δ : 1 . 49 ( s , 9h , 3xch 3 ); 3 . 18 ( t , 4h , 2xch 2 ); 3 . 59 ( t , 4h , 2xch 2 ); 4 . 44 ( q , 2h , ch 2 ); 6 . 98 ( d , 2h , j = 7 hz , ar -- h ); 7 . 38 ( d , 2h , j = 7 hz , ar -- h ); 7 . 69 ( s , 1h , het - h ). the title compound was obtained by deprotection of boc group of the above compound with 3m hydrochloric acid . 1 h nmr ( cdcl 3 ) δ : 1 . 73 ( s , 1h , n - h ); 3 . 00 - 3 . 20 ( m , 8h , 4xch 2 ); 4 . 44 ( q , 2h , ch 2 ); 6 . 95 - 7 . 00 ( m , 2h , ar -- h ); 7 . 34 - 7 . 39 ( m , 2h , ar -- h ); 7 . 68 ( s , 1h , het - h ). the title compound was prepared from ( 2r , 3s )- 2 -( 2 , 4 - difluorophenyl )- 3 - methyl - 2 -( 1h - 1 , 2 , 4 - triazol - 1 - yl ) methyloxirane iv and piperazino compound xxiii ( r = 2 , 2 , 2 - trifluoroethyl , x ═ h ) by following the similar procedure described for the example 36 . 1 h nmr ( cdcl 3 ) δ : 0 . 90 ( d , 3h , j = 6 . 3 hz , ch 3 ); 2 . 50 - 2 . 56 ( m , 2h , ch 2 ); 2 . 93 - 3 . 16 ( m , 7h ); 4 . 37 ( q , 2h , ch 2 ); 4 . 83 ( m , 2h , ch 2 ); 6 . 61 - 6 . 91 ( m , 4h , ar -- h ); 7 . 27 - 7 . 46 ( m , 3h , ar -- h ); 7 . 61 ( s , 1h , het - h ); 7 . 71 ( s , 1h , het - h ); 7 . 88 ( s , 1h , het - h ). fab - ms : 579 . 2 ( mh + ), calcd . c 26 h 27 o 2 f 5 n 8 578 . 55 . the title compound was prepared by alkylation of triazolone xxi ( x ═ h ) with 2 , 4 - difluorobenzyl bromide in the presence of potassium carbonate . after usual workup the product was obtained in quantitative yield as a colorless solid . 1 h nmr ( cdcl 3 ) δ : 1 . 49 ( 3 , 9h , 3xch 3 ); 3 . 17 ( t , 4h , 2xch 2 ); 3 . 59 ( t , 4h , 2xch 2 ); 5 . 04 ( s , 2h , ch 2 ); 6 . 78 - 7 . 01 ( m , 4h , ar -- h ); 7 . 29 - 7 . 45 ( m , 3h , ar -- h ); 7 . 63 ( s , 1h , het - h ). 2 -( 2 , 4 - difluorobenzyl )- 4 -[ 4 -( 4 - piperazin - 1 - yl )- 2h - 1 , 2 , 4 - triazol - 3 - one ( xxiii ; x ═ h . r = 2 , 4 - difluorobenzyl ): the title compound was obtained by deprotection of boc group of the above compound with 3n hydrochloric acid . 1 h nmr 3 ) δ : 1 . 70 ( s , 1h , n -- h ); 2 . 92 - 3 . 10 ( m , 8h , 4xch 2 ); 4 . 96 ( s , 2h , ch 2 ); 6 . 71 - 6 . 91 ( m , 4h , ar -- h ); 7 . 21 - 7 . 37 ( m , 3h , ar -- h ); 7 . 54 ( s , 1h , het - h ). the title compound was prepared from ( 2r , 3s )- 2 -( 2 , 4 - difluorophenyl )- 3 - methyl - 2 -( 1h - 1 , 2 , 4 - triazol - 1 - yl ) methyloxirane and piperazino compound xxiii ( r = 2 , 4 - difluorobenzyl , x ═ h ) by following the similar procedure described for the example 36 . 1 h nmr ( cdcl 3 ) δ : 0 . 91 ( d , 3h , j = 5 . 6 hz , ch 3 ); 2 . 49 - 2 . 57 ( m , 2h , ch 2 ); 2 . 91 - 3 . 14 ( m , 7h ); 4 . 73 - 4 . 91 ( m , 2h , ch 2 ); 4 . 97 ( s , 2h , ch 2 ); 5 . 09 ( s , 1h ); 6 . 60 - 6 . 90 ( m , 6h , ar -- h ); 7 . 25 - 7 . 45 ( m , 4h , ar -- h ); 7 . 54 ( s , 1h , het - h ); 7 . 70 ( s , 1h , het - h ); 7 . 87 ( s , 1h , het - h ). fab - ms : 623 . 1 ( mh + ); calcd . c 30 h 30 f 4 o 2 n 8 622 . 63 . the title compound was prepared by alkylation of triazolone xxi ( x ═ h ) with 4 -( trifluoromethoxy ) benzyl bromide in the presence of potassium carbonate . after usual workup the product was obtained in 90 % yield as a colorless solid . 1 h nmr ( cdcl 3 ) δ : 1 . 49 ( s , 9h , 3xch 3 ), 3 . 13 - 3 . 18 ( m , 4h , 2xch 2 ); 3 . 56 - 3 . 61 ( m , 4h , 2xch 2 ); 5 . 00 ( s , 2h , ch 2 ); 6 . 94 - 6 . 99 ( m , 2h , ar -- h ); 7 . 17 - 7 . 22 ( m , 2h , ar -- h ) 7 . 38 - 7 . 47 ( m , 4h , ar -- h ); 7 . 63 ( s , 1h , het - h ). the title compound was obtained by removal of t - boc group of the aboove compound with 3m hydrochloric acid . 1 h nmr ( cdcl 3 ) δ : 1 . 64 ( s , 1h , n -- h ); 3 . 01 - 3 . 20 ( m , 8h , 4xch 2 ); 5 . 01 ( s , 2h , ch 2 ); 6 . 95 - 6 . 99 ( m , 2h , ar -- h ); 7 . 18 - 7 . 22 ( m , 2h , ar -- h ), 7 . 34 - 7 . 47 ( m , 4h , ar -- h ); 7 . 61 ( s , 1h , het - h ). the title compound was prepared from ( 2r , 3s )- 2 -( 2 , 4 - difluorophenyl )- 3 - methyl - 2 -( 1h - 1 , 2 , 4 - triazol - 1 - yl ) methyloxirane and piperazino compound xxiii [ r = 4 -( trifluoromethoxy ) benzyl ; x ═ h ] by following the similar procedure described for the example 36 . 1 h nmr ( cdcl 3 ) δ : 0 . 98 ( d , 3h , j = 5 . 7 hz , ch 3 ); 2 . 57 - 2 . 65 ( m , 2h , ch 2 ); 2 . 99 - 3 . 22 ( m , 7h ); 4 . 82 - 4 . 92 ( m , 2h , ch 2 ) 5 . 01 ( s , 2h , ch 2 ); 5 . 15 ( s , 1h ); 6 . 68 - 7 . 54 ( m , 11h , ar -- h ); 7 . 62 ( s , 1h , het - h ); 7 . 79 ( s , 1h , het - h ); 7 . 95 ( s , 1h , het - h ). fab - ms : 671 . 3 ( mh + ), calcd . c 32 h 31 o 3 f 5 n 8 670 . 64 . the title compound was prepared by alkylation of triazolone xxi ( x ═ h ) with 4 - methoxybenzyl bromide in dmf in the presence of potassium carbonate . 1 h nmr ( cdcl 3 ) δ : 1 . 49 ( s , 9h , 3xch 3 ); 3 . 12 - 3 . 17 ( m , 4h , 2xch 2 ); 3 . 55 - 3 . 61 ( m , 4h , 2xch 2 ); 3 . 77 ( s , 3h , och 3 ); 4 . 94 ( s , 2h , ch 2 ); 6 . 83 - 6 . 99 ( m , 4h , ar -- h ); 7 . 32 - 7 . 41 ( m , 4h , ar -- h ); 7 . 59 ( s , 1h , het - h ). the title compound was obtained by deprotection of t - boc group of 2 -( 4 - methoxybenzyl )- 4 -[ 4 -( 4 - tert - boc - piperazin - 1 - yl ) phenyl - 2h - 1 , 2 , 4 - triazol - 3 - one with 3m hydrochloric acid . 1 h nmr ( cdcl 3 ) δ : 1 . 62 ( s , 1h , n - h ); 3 . 01 - 3 . 19 ( m , 8h , 4xch 2 ); 3 . 79 ( s , 3h , och 3 ); 4 . 95 ( s , 2h , ch 2 ); 6 . 86 - 6 . 99 ( m , 4h , ar -- h ); 7 . 35 - 7 . 39 ( m , 4h , ar -- h ); 7 . 57 ( s , 1h , het - h ). the title compound was prepared from ( 2r , 3s )- 2 -( 2 , 4 - difluorophenyl )- 3 - methyl - 2 -( 1h - 1 , 2 , 4 - triazol - 1 - yl ) methyloxirane iv and piperazino compound xxiii ( r = 4 - methoxybenzyl ; x ═ h ) by following the similar procedure described for the example 36 . 1 h nmr ( cdcl 3 ) δ : 0 . 96 ( d , 3h , j = 6 . 8 hz , ch 3 ); 2 . 56 - 2 . 62 ( m , 2h ch 2 ); 2 . 99 - 3 . 21 ( m , 7h ); 3 . 79 ( s , 3h , och 3 ); 4 . 89 - 4 . 99 ( m , 2h , 2 ); 4 . 95 ( s , 2h , ch 2 ); 5 . 14 ( s , 1h ); 6 . 68 - 6 . 97 ( m , 6h , ar -- h ); 7 . 35 - 7 . 53 ( m , 5h , ar -- h ), 7 . 58 ( s , 1h , het - h ); 7 . 78 ( s , 1h , het - h ); 7 . 95 ( s , 1h , het - h ). fab - ms : 617 . 0 ( mh + ), calcd . c 32 h 34 o 3 f 2 n 8 616 . 67 . the title compound was prepared by alkylation of triazolone xxi ( x ═ h ) with 2 , 4 - bis ( trifluoromethyl ) benzyl bromide in the presence of potassium carbonate . after usual workup the product was obtained in 76 % yield as a colorless solid . 1 h nmr ( cdcl 3 ) δ : 1 . 49 ( s , 9h , 3xch 3 ); 3 . 15 - 3 . 20 ( m , 4h , 2xch 2 ); 3 . 57 - 3 . 63 ( m , 4h , 2xch 2 ); 5 . 31 ( s , 2h , ch 2 ); 6 . 98 - 7 . 02 ( m , 2h , ar -- h ); 7 . 40 - 7 . 53 ( m , 3h , ar -- h ); 7 . 72 ( s , 1h , het - h ); 7 . 77 - 7 . 95 ( m , 2h , ar -- h ). the title compound was obtained by deprotection of t - boc group of 4 [- 4 -( 4 - tert - boc - piperazin - 1 - yl ) phenyl ]- 2 -( 2 , 4 - bis - trifluoromethyl ) benzyl - 2h - 1 , 2 , 4 - triazol - 3 - one with 3m hydrochloric acid . 1 h nmr ( cdcl 3 ) δ : 1 . 88 ( s , 1h , nh ); 3 . 02 - 3 . 21 ( m , 8h , 4xch 2 ); 5 . 31 ( s , 2h , ch 2 ); 6 . 96 - 7 . 01 ( m , 2h , ar -- h ); 7 . 39 - 7 . 95 ( m , 5h , ar -- h ); 7 . 70 ( s , 1h , het - h ). the title compound was prepared from ( 2r , 3s )- 2 -( 2 , 4 - difluorophenyl )- 3 - methyl - 2 -( 1h - 1 , 2 , 4 - triazol - 1 - yl ) methyloxirane iv and piperazino compound xxiii [ r = 2 , 4 - bis ( trifluromethyl ) benzyl ; x ═ h ] by following the similar procedure described for the example 36 . 1 h nmr ( cdcl 3 ) δ : 0 . 99 ( d , 3h , j = 6 . 8 hz , ch 3 ); 2 . 58 - 2 . 66 ( m , 2h , ch 2 ); 3 . 01 - 3 . 24 ( m , 7h ); 4 . 82 - 5 . 00 ( m , 2h , ch 2 ); 5 . 14 ( s , 1h ); 5 . 31 ( s , 2h , ch 2 ), 6 . 69 - 6 . 83 ( m , 2h , ar -- h ); 6 . 96 - 7 . 00 ( m , 2h , ar -- h ) 7 . 40 - 7 . 53 ( m , 4h , ar -- h ); 7 . 72 ( s , 1h , het - h ) 7 . 77 - 7 . 81 ( m , 2h , ar -- h & amp ; het - h ); 7 . 95 ( s , 2h , ar -- h & amp ; het - h ). the title compound was prepared by alkylation of triazolone xxi ( x ═ h ) with 4 -( 2 , 2 , 3 , 3 - tetrafluoropropoxy ) benzyl bromide in the presence of potassium carbonate . after usual workup the product was obtained in 81 % yield as a colorless solid . 1 h nmr ( cdcl 3 ) δ : 1 . 49 ( s , 9h , 3xch 3 ), 3 . 12 - 3 . 17 ( m , 4h , 2xch 2 ), 3 . 55 - 3 . 60 ( m , 4h , 2xch 2 ), 4 . 26 - 4 . 37 ( m , 2h , och 2 ), 4 . 94 ( s , 2h , ch 2 ), 5 . 76 - 6 . 36 ( m , 1h , cf 2 h ), 6 . 86 - 6 . 98 ( m , 4h , ar -- h ), 7 . 37 ( m , 4h , ar -- h ), 7 . 60 ( s , 1h , het - h ). the title compound was obtained by deprotection of t - boc group of the above compound with 3m hydrochloric acid . after usual workup the product was obtained in 98 % yield as colorless solid . 1 h nmr ( cdcl 3 ) δ : 1 . 87 ( s , 1h , nh ), 3 . 01 - 3 . 19 ( m , 8h , 4xch 2 ), 4 . 27 - 4 . 39 ( m , 2h , och 2 ), 4 . 96 ( s , 2h , ch 2 ), 5 . 77 - 6 . 35 ( m , 1h , cf 2 h ), 6 . 89 - 6 . 99 ( m , 4h , ar -- h ), 7 . 33 - 7 . 42 ( m , 4h , ar -- h ), 7 . 58 ( s , 1h , het - h ). the title compound was prepared from ( 2r , 3s )- 2 -( 2 , 4 - difluorophenyl )- 3 - methyl - 2 -( 1h - 1 , 2 , 4 - triazol - 1 - yl ) methyloxirane iv and piperazino compound xxiii [ r = 4 -( 2 , 2 , 3 , 3 - tetrafluoropropoxy ) benzyl ; x ═ h ] by following the similar procedure described for the example 36 . 1 h nmr ( cdcl 3 ) δ : 0 . 97 ( d , 3h , ch 3 ), 2 . 57 - 2 . 62 ( m , 2h , 2 ), 2 . 99 - 3 . 22 ( m , 7h ), 4 . 27 - 4 . 38 ( m , 2h , ch 2 ), 4 . 81 - 4 . 99 ( m , 2h , ch 2 ), 4 . 96 ( s , 2h , ch 2 ), 5 . 15 ( s , 1h , oh ), 5 . 77 - 6 . 35 ( m , 1h , cf 2 h ), 6 . 68 - 6 . 98 ( m , 6h , ar -- h ), 7 . 35 - 7 . 53 ( m , 5h , ar -- h ), 7 . 59 ( s , 1h , het - h ), 7 . 78 ( s , 1h , het - h ), 7 . 95 ( s , 1h , het - h ). fab - ms : 717 . 3 ( mh + ), calcd c 34 h 34 f 6 o 3 n 8 716 . 69 . the title compound was prepared by alkylation of triazolone xxi ( x ═ f ) with ( trifluoromethyl ) benzyl bromide in the presence of potassium carbonate . after usual workup and purification on a column of silica gel , the title compound was obtained in 95 % yield as a colorless solid . 1 h nmr ( cdcl 3 ) δ : 1 . 48 ( s , 9h , 3xch 3 ), 3 . 04 ( m , 4h , 2xch 2 ), 3 . 60 ( m , 4h , 2xch 2 ), 5 . 06 ( s , 2h , ch 2 ), 6 . 99 ( m , 1h , ar -- h ), 7 . 2 - 7 . 4 ( m , 2h , ar -- h ), 7 . 49 - 7 . 62 ( m , 4h , ar -- h ), 7 . 64 ( s , 1h , het - h ). the title compound was obtained in 96 % yield by deprotection of boc group of the above compound with 3m hydrochloric acid . 1 h nmr ( cdcl 3 ) δ : 3 . 0 ( s , 8h , 4xch 2 ), 5 . 05 ( s , 2h , ch 2 ), 7 . 0 ( m , 1h , ar -- h ), 7 . 2 - 7 . 38 ( m , 2h , ar -- h ), 7 . 48 - 7 . 62 ( m , 4h , ar -- h ), 7 . 65 ( s , 1h , het - h ). the title compound was prepared from ( 2r , 3s )- 2 -( 2 , 4 - difluorophenyl )- 3 - methyl - 2 -( 1h - 1 , 2 , 4 - triazol - 1 - yl ) methyloxirane iv and piperazino compound xxiii [ r = 4 -( trifluoromethyl ) benzyl ; x ═ f ] by following the similar procedure described for the example 36 . 1 h nmr ( cdcl 3 ) δ : 0 . 99 ( d , 3h , ch 3 ), 2 . 65 ( m , 2h , ch 2 ), 2 . 95 - 3 . 2 ( m , 7h , 3xch 2 and ch ), 4 . 90 ( ab q , 2h , ch 2 ), 5 . 07 ( s , 2h , ch 2 ), 5 . 15 ( s , 1h , oh ), 6 . 7 - 6 . 85 ( m , 2h , ar -- h ), 7 . 04 ( m , 1h , ar -- h ), 7 . 2 - 7 . 62 ( m , 7h , ar -- h ), 7 . 64 ( s , 1h , het - h ), 7 . 79 ( s , 1h , het - h ), 7 . 95 ( s , 1h , het - h ). fab - ms : 673 . 8 ( mh + ), calcd . c 32 h 30 f 6 n 8 o 2 672 . 634