as disclosed above , the 11 - step process for preparing compound ( 12 ) is shown in chart 2 . these steps are as follows : step 1 -- the first step ( aromatic nucleophilic substitution ) in the synthetic approach is described by j . bourdais and c . mahieu , compt . redux [ c ], 263 , 84 ( 1966 ). also see j . bourdais and c . germain , tet . letters , 195 ( 1970 ). the various r 1 groups can be introduced on the phenol precursor of ( 1 ) by procedures described in the literature ( appropriate references detailed under step 8 ). the various malonates , β - keto esters , and β - diketones employed are all known compounds . step 2 -- reduction . when r 2 = alkoxy , diisobutylaluminum hydride is the reagent of choice . reaction conditions are quite specific ( see example 1 ) for optimum yields . when r 2 = alkyl or phenyl , standard reduction procedures employing sodium borohydride can be employed . step 3 -- functional group interchange . the chemistry described specifically herein is in the case of x = oso 2 ch 3 . the mesylate or tosylate ( for example ) can be prepared under standard conditions known in the art employing pyridine ( with or without solvent , such as methylene chloride ) or other acid acceptors such as trialkylamines ( with solvent ) and the corresponding sulfonyl chloride . the halogen analogs of 4 can be prepared under standard procedures known in the art such as ph 3 p / ccl 4 ( cbr 4 ) and n - iodosuccinimide / triphenylphosphine . step 4 -- reduction - cyclization . this step is a novel preparation of indolines ( dihydroindoles ). this involves the reduction of the nitro to the amino group with concomitant intramolecular cyclization to give ( 5 ). the reduction step described in detail herein utilizes h 2 , pto 2 in alcohol in the presence of a tertiary amine . these are standard hydrogenation conditions in the art . palladium or nickel catalysts can also be employed and bases other than a tertiary amine , such as pyridine , can be utilized . alternate reducing conditions can employ fe or ticl 3 in acid or sncl 2 . this may then require a separate step involving treatment with base to induce the cyclization to ( 5 ). an example of a reduction with iron is the use of fe / ch 3 co 2 h / ch 3 ch 2 oh ( g . s . ponticello and j . j . baldwin , j . org . chem ., 44 , 4003 ( 1979 ). these conditions would be required if r 1 = ch 2 ph or -- ch 2 ch = ch 2 . the concept of nitro reduction followed by in situ cyclization to indoles is advanced by a . d . batcho and w . leimgruber , german offen . 2057840 ( 1971 ), which is a significant improvement over the older reissert procedure of reductive cyclization to indoles . ( see r . j . sundberg , the chemistry of indoles , pp . 176 - 183 . academic press , n . y ., 1970 ). step 5 -- substitution of labile group . this step is required due to the incompatibility of x with the chemistry of step 8 . it involves the replacement of x with an acetate or the conjugate base of a c 1 - c 5 alkyl carboxylic acid under standard conditions ( alkali carboxylate in acetone , dmf , or alcohol ). since some hydrolysis can occur when x = oso 2 ch 3 , the reaction mixture is treated with acetic anhydride prior to isolation of ( 6 ). step 6 -- nitration can be performed under a variety of conditions described in the literature including nitric acid in acetic acid , acetic anhydride , sulfuric acid , acetic acid / h 2 o , alcohol , and nitroalkanes . the regioselectivity of this reaction is supported by the spectroscopic data obtained . step 7 -- reduction of the nitro to the amino group follows the same chemical description given in step 4 with the omission of base . step 8 -- indole synthesis . this procedure is based generally on the indole chemistry of gassman [ p . g . gassman , et . al ., j . am . chem . soc ., 96 , 5494 , 5508 , 5512 ( 1974 )]. several modifications are required which are not disclosed or suggested in gassman &# 39 ; s work . the sequence of the chemical events and some of the intermediates are depicted in chart 3 . the α - thiomethyl esters are known . this process deviates from the published gassman route by employing the chlorosulfonium complex , a , and reacting it with the aniline , ( 6 ); gassman prepares the chloroamine of an aniline and reacts it with the thioether in making oxindoles . secondly , two different bases are employed in the process , whereas gassman uses two equivalents of the aniline followed by a base 2 . although triethylamine , diisopropylethylamine , bis ( 1 , 8 - dimethyl amino ) naphthalene , and the like both work for base 1 and base 2 , the preferred for base 1 is bis ( 1 , 8 - dimethylamine ) naphthalene , and triethylamine for base 2 . different solvents such as chloroform , acetonitrile , tetrahydrofuran ( thf ), and methylene chloride can be used , the latter is preferred . the temperature range is from - 50 ° to - 80 ° and the reaction is run under an inert atmosphere . the cyclization to the oxindole b is best promoted by acid catalysis as described by gassman ( 2n hcl , ether and / or ethyl acetate ). the final reduction to ( 9 ) ( reductive elimination ) can be accomplished with lithium aluminum hydride ( as described by gassman ) or diborane type reagents , the latter being far superior . the preferred reagent is ( ch 3 ) 2 s . bh 3 in thf at room temperature for 24 hours . step 9 -- this deprotection step ( removal of r 1 ) is described in detail for r 1 = ch 3 in example 8 . although there are a number of procedures described in the art involving methyl ether cleavage , only alkyl mercaptide in hexamethylphosphorictriamide ( hmpa ) under an inert atmosphere ( 95 °- 110 °) have been found to be effective [ s . c . welch and a . s . c . p . rao , tet . letters , 505 ( 1977 ) and t . r . kelly , h . m . dali , and w - g . tsang , tet . letters , 3859 ( 1977 ), or me 2 s . bbr 3 in dichloroethane ( p . g . willard and c . b . fryhle , tet . letters , 3731 ( 1980 )]. when r 1 = ch 2 ph , standard hydrogenolysis conditions suffice to deprotect ( h 2 , pd / c ) [ org . reactions , 7 , 263 ( 1953 )]. when r 1 = ch 2 sch 3 , mercuric chloride in acetonitrile / h 2 o removes the ether ( r . a . holton and r . g . davis , tet . letters , 533 ( 1977 ). when r 1 = ch 2 och 3 , moderate acid will generate the phenol - 10 , such as acetic acid [ j . med . chem ., 9 , 1 ( 1966 ) or synthesis , 244 ( 1976 )]. in fact , this protecting group may be lost in step 6 , however , it can be reintroduced prior to step 7 under standard conditions . when r 1 =-- ch 2 och 2 ch 2 och 3 , the phenol can be generated by znbr 2 or ticl 4 in ch 2 cl 2 [ tet . letters , 809 ( 1976 )]. when r 1 =-- ch 2 ch ═ ch 2 , several two - step procedures will deprotect the ether ( pd / c in alcohol / ang . chem . int . ed ., 15 , 558 ( 1976 ); seo 2 , ch 3 co 2 h in dioxane / tet . letters , 2885 ( 1970 ); t - buok , dmso followed by h 2 so 4 in acetone / j . chem . soc ., 1903 ( 1965 ); rhcl ( pph 3 ) 3 , dabco in alcohol followed by ph2 [ j . org . chem ., 38 , 3224 ( 1973 )]. when r 1 =-- ch 2 ch 2 si ( r 2 ) 3 deprotection is effected by bu 4 nf [ h . gerlach , et . al ., helv . chim . acta , 60 , 3039 ( 1977 )]. step 11 -- this step ( when x = br ) is promoted by contact with silica gel as well as occurs on standing in protic solvents . this reaction will also proceed in the presence of such bases as tertiary amines , pyridine , t - butoxide , and the like and weak aqueous bases such as bicarbonate and carbonate . the following examples are illustrative of the products and process of the invention , but are not to be construed as limiting . all percentages are by weight and all solvent mixture proportions are by volume unless otherwise noted . to 400 ml of thf under n 2 cooled in an ice - water bath is added 100 g of dibal * ( 0 . 70 mole ) in 400 ml of toluene . to this stirred solution is added 33 . 0 g ( 0 . 105 mole ) of the arylmalonate ( 2 ) in 100 ml of thf . the rate of addition is controlled to keep the reaction temperature below 5 °. after the addition is complete the ice bath is removed . the reaction is quenched after 3 hours total reaction time by the portion - wise addition of the solution to cold 3n hcl with stirring ( approximately 1 . 5 l ). the mixture is then extracted with 1 l of etoac followed by 1000 ml ch 2 cl 2 . the combined organic phases are dried over na 2 so 4 and concentrated to a red - brown residue ( 21 . 2 g ). chromatography of the residue on 500 g silica gel with 60 % etoac / hexane → 100 % etoac gradient eluent affords 11 . 7 g ( 49 % yield ) of the diol ( 3 ) ( u - 62 , 598 ) as a light red oil ( solidifies on standing in the freezer ). nmr ( cdcl 3 ): 7 . 5 - 7 . 0 ( m , 3h ), 3 . 80 ( s , 3h ), 4 . 0 - 3 . 3 ( m , 7h -- includes 2 oh ). ms : calc . for c 10 h 13 no 5 : 227 . 0794 . found : 227 . 0780 . analysis : calc : c , 52 . 86 , h , 5 . 76 , n , 6 . 16 . found : c , 53 . 40 , h , 5 . 77 , n , 5 . 99 . to 4 . 7 g ( 0 . 2 moles ) of the diol ( 3 ) in 100 ml of dry pyridine under n 2 at 0 °- 5 ° is added with stirring 6 . 8 g ( 0 . 06 mole ) of methanesulfonyl chloride . after stirring at 5 ° for 30 minutes followed by room temperature for 90 minutes , the solution is concentrated in vacuo , then taken up in ch 2 cl 2 / 1n hcl . the organic phase is separated , dried over na 2 so 4 , concentrated to a residue . trituration with etoac affords an off - white solid and the mother liquors can be chromatographed on silica gel ( etoac eluent ) to afford a total yield of 6 . 65 g ( 86 % yield ), m . p . 122 °- 3 ° ( recrystallized from acetone ) of compound ( 4 ), bismesylate ( u - 62 , 597 ). nmr ( acet - d 6 ): 7 . 7 - 7 . 2 ( m , 3h ), 4 . 62 ( d , 4h , j = j hz ), 4 . 11 ( t , 1h , j = 7 hz ), 3 . 92 ( s , 3h ), 3 . 06 ( s , 6h ). analysis : calc for c 12 h 17 no 9 s 2 : calc : c , 37 . 59 , h , 4 . 47 , n , 3 . 65 . found : c , 37 . 35 , h , 4 . 44 , n , 3 . 59 . this compound was assayed by a standard tube dilution assay against l1210 mouse leukemia cells in culture and gave the following results : to 1 . 91 g ( 0 . 005 mole ) of compound ( 4 ) in 30 ml of thf , 20 ml of etoac , and 150 ml of absolute ethanol is added 1 . 5 ml of triethylamine and 400 mg of pto 2 . this solution is placed under 7 - 10 psi h 2 pressure with shaking for 30 minutes . the reaction solution is then filtrated over celite and concentrated in vacuo . after several ch 2 cl 2 azeotropes in vacuo , the residue is ultimately taken up in 100 ml of ch 2 cl 2 and cooled under n 2 in an ice bath . to the stirred solution is added 1 . 5 ml of triethylamine followed by the dropwise addition of 900 μl methane sulfonylchloride . after stirring for 30 minutes , the solution is allowed to come to room temperature for 60 minutes . the solution is then washed with 1n hcl , dried over na 2 so 4 , and concentrated . the residue is rapidly chromatographed on 150 g silica gel with 500 ml of 60 % etoac / hexane followed by 1000 ml of 80 % elution ; recovered 1 . 3 g ( 78 % yield ) of an off - white solid , m . p . 122 °- 3 ° ( recrystallized from ethanol ) of compound ( 5 ), the 6 - methoxyindoline bismesylate ( u - 62 , 586 ). nmr ( dmf - d 7 ): 7 . 36 ( d , 1h , j = 8 . 5 hz ), 7 . 00 ( d , 1h , j = 2 hz ), 6 . 69 ( dd , 1h , j = 2 , 8 . 5 hz ), 4 . 47 ( 2h , d , j = 6 hz ), 4 . 3 - 3 . 6 ( m , 3h ), 3 . 80 ( s , 3h ), 3 . 20 ( s , 3h ), 3 . 07 ( s , 3h ). analysis : calc for c 12 h 17 ns 2 o 6 : calc : c , 42 . 97 , h , 5 . 11 , n , 4 . 18 . found : c , 42 . 87 , h , 5 . 27 , n , 4 . 29 . this compound was assayed by a standard tube dilution assay against l1210 mouse leukemia cells in culture and gave the following results : to 13 . 0 g ( 39 mmol ) of the 6 - methoxy indoline bismesylate ( 5 ) in 30 ml of dmf is added 800 ml of abs . ethanol followed by 32 g of sodium acetate . this hereogeneous solution is refluxed under n 2 for 24 hours , cooled , and concentrated in vacuo . the residue is treated with 100 ml of acetic anhydride for 2 hours ( stirring at room temperature ), then concentrated in vacuo . the residue is taken up in ch 2 cl 2 / h 2 o and the organic phase is separated , dried over na 2 so 4 , filtered through charcoal , and concentrated to an oil which solidifies ; 11 . 6 g of compound ( 6 ), the 6 - methoxy indoline acetate ( 100 %; if necessary , further purification is possible with silica gel chromatography employing 60 % etoac / hexane eluent ). nmr ( cdcl 3 ): 7 . 17 ( d , 1h , j = 8 . 5 hz ), 7 . 02 ( d , 1h , j = 2 hz ), 6 . 60 ( dd , 1h , j = 2 , 8 . 5 hz ), 4 . 18 ( d , 2h , j = 6 hz ), 4 . 1 - 3 . 4 ( m , 3h ), 3 . 78 ( s , 3h ), 2 . 91 ( s , 3h ), 2 . 05 ( s , 3h ). analysis : calc for c 13 h 17 no 5 s : calc : c , 52 . 16 , h , 5 . 76 , n , 4 . 68 . found : c , 52 . 13 , h , 5 . 79 , n , 5 . 27 . to 500 mg ( 1 . 67 mmole ) of the 6 - methoxy indoline acetate ( 6 ) in 20 ml of nitromethane is added 90 μl of 90 % hno 3 . the cooled reaction solution ( o °- 5 °) is stirred for 30 minutes , then warmed to room temperature for 30 minutes . the solution is diluted with ch 2 cl 2 and aqueous sodium bicarbonate . the organic phase is separated , dried over na 2 so 4 , and concentrated . the residue is chromatographed on 50 g silica gel ( 60 % etoac / hexane eluent → 100 % etoac ) yield ; 440 mg ( 76 % yield ) of a yellow solid , m . p . 175 °- 7 ° ( recrystallized from ethanol ) of compound ( 7 ), the 5 - nitro - 6 - methoxy indoline acetate ( u - 62 , 696 ). nmr ( dmf - d 7 ): 7 . 91 ( s , 1h ), 7 . 20 ( s , 1h ), 4 . 27 ( d , 2h , j = 6 hz ), 4 . 3 - 3 . 7 ( m , 3h ), 3 . 98 ( s , 3h ), 3 . 17 ( s , 3h ), 2 . 07 ( s , 3h ). analysis : calc for c 13 h 16 n 2 o 7 s : calc : c , 45 . 34 , h , 4 . 68 , n , 8 . 14 . found : c , 44 . 81 , h , 4 . 77 , n , 8 . 16 . this compound was assayed by a standard tube dilution assay against l1210 mouse leukemia cells in culture and gave the following results : to 4 . 5 g ( 13 mmole ) of the 5 - nitro - 6 - methoxy indoline acetate ( 7 ) in 50 ml of thf and 150 ml of absolute ethanol is added 500 mg pto 2 and shaken under 10 psi of h 2 until uptake ceases ( approximately 60 minutes ). filter and concentrate in vacuo . upon concentration , 3 . 0 g of product precipitates out . this is filtered off and the mother liquors rapidly chromatographed on 100 g silica gel with etoac eluent to afford an additional 0 . 6 g . the total yield ( 3 . 6 g ) is 88 %; m . p . 134 °- 5 ° ( from acetone / cyclohexane ) of compound ( 8 ), the 5 - amino - 6 - methoxy indoline acetate ( u - 62 , 697 ). nmr ( cdcl 3 ): 7 . 02 ( s , 1h ), 6 . 65 ( s , 1h ), 4 . 16 ( d , 2h , j = 6 hz ), 4 . 1 - 3 . 5 ( m , 3h ), 3 . 83 ( s , 3h ), 3 . 6 ( br . s , 2h ), 2 . 83 ( s , 3h ). analysis : calc for c 13 h 18 n 2 o 5 s : calc : c , 49 . 67 , h , 5 . 77 , n , 8 . 91 . found : c , 49 . 74 , h , 5 . 72 , h , 8 . 94 . this compound was assayed by a standard tube dilution assay against l1210 mouse leukemia cells in culture and gave the following results : to 14 ml of dry ch 2 cl 2 under n 2 at - 75 ° is added 6 . 0 ml of a cl 2 / ch 2 cl 2 solution ( 20 μl cl 2 / ml ch 2 cl 2 ). to this stirred solution is added 370 μl ( 2 . 5 mmole ) of ch 3 ( ch 3 s ) chco 2 c 2 h 5 ( prepared from ch 3 ( br ) chco 2 c 2 h 5 and methyl mercaptide by the procedure of e . h . wick , t . yamanishi , h . c . wertheimer , y . e . hoff , g . f . proctor , and s . a . goldblith , j . agr . food chem ., 9 , 289 ( 1961 )). after 5 minutes a solution of 470 mg ( 2 . 2 mmole ) of 1 , 8 - bisdimethylaminonaphthalene and 628 mg ( 2 . 0 mmole ) of the anilinoidoline ( 8 ) in 3 . 0 ml of dry ch 2 cl 2 is added dropwise over 15 minutes . the red solution is stirred for 2 hours at - 75 °, then 350 μl of triethylamine in 650 μl of ch 2 cl 2 is added dropwise over several minutes . the cooling bath is removed . when the reaction solution reaches room temperature it is briefly concentrated in vacuo . to the residue is added 5 ml etoac , 25 ml of ether and 6 ml of 2n hcl and stirred vigorously for 2 hours . the organic phase is separated and the aqueous is extracted with 1 : 1 etoac / et 2 o . the organics are combined , dried over na 2 so 4 and concentrated . at this point the residue is taken up in 10 ml of thf and treated with 3 . 0 ml of 2m bh 3 . sme 2 overnight at room temperature under n 2 . alternatively the diastereomeric oxindoles ( b ) derived from the acid treatment can be isolated at this point by silica gel chromatography ( 50 g ; 60 % etoac / hexane to 90 % etoac / hexane ). gs - ms : m / e m + 414 ( 15 %), 227 ( 100 %)- 2 &# 39 ; 1 % se - 30 nmr ( cdcl 3 ): 8 . 4 ( br . s , 1h ), 7 . 11 ( s , 1h ), 4 . 5 - 3 . 7 ( m , 5h ), 3 . 90 ( s , 3h ), 2 . 95 ( s , 3h ), 2 . 10 ( s , 3h ), 1 . 92 ( s , 3h ), 1 . 82 ( s , 3h )- major diasteromer ( 2 . 5 / l ); minor diastereomer shows the following differences - 1 . 99 ( s , 3h ), 1 . 76 ( s , 3h ) for -- sch 3 and -- ch 3 , the nh is is at 7 . 7 and the ch 2 region is 4 . 3 - 3 . 6 ppm . the aqueous phase from the acid treatment can be neutralized and extracted with ch 2 cl 2 . the ch 2 cl 2 solution can be dried , concentrated , and chromatographed on silica gel with 50 % acetone / cyclohexane to give 40 % recovery of starting material ( anilinoindoline ) and 20 % deacylated starting material . the boranedimethylsulfide reductive elimination ( on b ) reaction is worked up by quenching with 1n hcl until gas evolution ceases and taking up in ch 2 cl 2 / h 2 o . the separated organic phase is dried over na 2 so 4 and concentrated . the residue is chromatographed on silica gel ( 50 % acetone / cyclohexane ) to afford 155 mg of product ( 9 ); 25 % isolated yield - 85 % based on recovered starting material ), m . p . 182 °- 183 ° ( phase change at 160 °, recrystallized from chloroform ), the 4 , 5 - pyrrollo - 6 - methoxy indoline ( 9 ) ( u - 62 , 233 ). nmr ( cdcl 3 ): 8 . 3 ( br . s , 1h ), 6 . 96 ( s , 2h ), 4 . 2 - 3 . 5 ( m , 5h + oh ), 3 . 92 ( s , 3h ), 2 . 87 ( s , 3h ), 2 . 41 ( s , 3h ). analysis : calc for c 14 h 18 n 2 o 4 s : calc : c , 54 . 17 , h , 5 . 84 , n , 9 . 03 . found : c , 53 . 49 , h , 5 . 96 , n , 9 . 42 . gc - ms : of o - acetate - m / e m + 352 ( 13 %), 213 ( 100 %)- 2 &# 39 ;- 1 % se - 30 , temperature 150 °- 260 ° ( 10 °/ minute ); single peak this compound was assayed by a standard tube dilution assay against l1210 mouse leukemia cells in culture and gave the following results : to 10 ml of dry , degassed hmpa ( hexamethylphosphorictriamide ) under n 2 at room temperature is added 350 μl of butyl mercaptan . the solution is cooled in an ice - water bath and 2 . 0 ml of 1 . 5m n - buli in hexane is added dropwise . after allowing the reaction to come to room temperature 100 mg ( 0 . 3 mmole ) of the indole ( 9 ) is added with stirring . the solution is heated to 100 ° for 2 . 5 hours . the reaction is followed by tlc ( 50 % acetone / cyclohexane ) and when conversion appears approximately 75 % complete ( by vanillin / phosphoric acid spray ), heating is terminated . the cooled solution is poured into 1n hcl ( 100 ml ) and extracted with 20 ml etoac . the separated organic phase is washed with additional 50 ml of water . the aqueous phases are combined and back - extracted with 20 ml of etoac . the organic phases are then combined , dried over na 2 so 4 , concentrated in vacuo , and applied to a 100 g silica gel column and eluted with 50 % acetone / cyclohexane . afforded are 25 mg of starting material and 45 mg of product ( 10 ) 44 % isolated yield , 69 % based on recovered s . m . ), the 4 , 5 - pyrrolo - 6 - hydroxy indoline ( u - 62 , 370 ). nmr ( acet - d 6 ): 7 . 8 ( br . s , 1h ), 7 . 03 ( s , 1h ), 6 . 83 ( s , 1h ), 4 . 25 - 3 . 25 ( m , 5h ), 2 . 86 ( s , 3h ), 2 . 36 ( s , 3h ). this product was treated with acetic anhydride ( 1 . 0 ml ) and 20 mg of naoac overnight , then taken up in ch 2 cl 2 / h 2 o . the organic phase was separated , dried over na 2 so 4 , and concentrated . nmr ( cdcl 3 ): 7 . 8 ( br . s , 1h ), 7 . 16 ( s , 1h ), 6 . 97 ( s , 1h ), 4 . 42 , 4 . 20 ( dd , 2h ), 4 . 2 - 3 . 7 ( m , 3h ), 2 . 86 ( s , 3h ), 2 . 40 ( s , 3h ), 2 . 35 ( s , 3h ), 2 . 06 ( s , 3h ). this compound was assayed by a standard tube dilution assay against l1210 mouse leukemia cells in culture and gave the following results : to 25 mg ( 65 μmole ) of the substrate alcohol in 1 . 0 ml of dry acetonitrile under n 2 at room temperature is added 33 mg ( 100 μmole ) of cbr 4 and 26 mg ( 100 μmole ) of triphenyl phosphine ( ph 3 p ). after stirring for 30 minutes an additional 11 mg cbr 4 and 8 mg of ph 3 p are added . the reaction is taken up in ch 2 cl 2 / h 2 o after 60 minutes ( total ). the organic phase is separated , dried over na 2 so 4 , and concentrated . the residue is placed on three 20 × 20 cm 250μ silica gel plates and eluted with 50 % acetone / cyclohexane . approximately 8 mg of the higher r f product ( 0 . 64 ; alcohol r f = 0 . 45 ) is recovered , compound ( 11 ), the 4 , 5 - pyrrolo - 6 - hydroxy indoline bromide ( u - 62 , 694 ). nmr ( cdcl 3 ): 8 . 5 ( br . s , 1h ), 7 . 1 ( s , 1h ), 6 . 9 ( s , 1h ), 4 . 23 ( d , 2h , j = 6 hz ), 4 . 0 - 3 . 5 ( m , 3h ), 2 . 89 ( s , 3h ), 2 . 38 ( s , 3h ). ms : calc . for c 16 h 23 n 2 o 3 79 brssi = 430 . 0382 , found 430 . 0375 ( mono - tms ); m / e m + 430 / 432 ( 14 %), 271 ( 90 %), 147 ( 100 %). this compound was assayed by a standard tube dilution assay against l1210 mouse leukemia cells in culture and gave the following results : to 20 mg ( 65 μmole ) of the alcohol substrate ( 10 ) in 1 . 0 ml pyridine in an ice bath with stirring under n 2 is added 8 μl of methanesulfonyl chloride ( 70 μmole ). after 30 minutes an additional 2 μl of ch 3 so 2 cl is added and worked up with 2n hcl / ch 2 cl 2 after 60 minutes total reaction time . the organic phase is separated , dried over na 2 so 4 , and concentrated . tlc indicates mostly lower r f product ( 0 . 28 in 50 % acetone / cyclohexane , alcohol r f = 0 . 46 ) and some higher r f product ( 0 . 66 ). preparative tlc ( 3 - 20 × 20 cm 250μ silica gel plates ) affords 2 mg of higher r f material ( nmr indicated only one ch 3 so 2 group ; it is probably the chloride ) and 9 mg of the lower r f material , compound ( 11 ) ( u - 62 , 695 ). nmr ( acet - d 6 ): 8 . 6 ( br . s , 1h ), 6 . 97 ( s , 1h ), 6 . 74 ( s , 1h ), 4 . 3 ( m , 2h ), 4 . 1 - 3 . 6 ( m , 3h ), 2 . 96 ( s , 3h ), 2 . 79 ( s , 3h ), 2 . 26 ( s , 3h ). this compound was assayed by a standard tube dilution assay against l1210 mouse leukemia cells in culture and gave the following results : in following the procedure to prepare the 4 , 5 - pyrrolo - 6 - hydroxy indoline bromide ( step 10 ), if the reaction mixture prior to work - up is concentrated in vacuo and applied to thick - layer silica gel plates directly , instead of isolating the higher r f ( 0 . 64 ) product bromide , a new lower r f band ( 0 . 32 ) is noted and recovered as compound ( 12 ). nmr ( cdcl 3 ): 9 . 5 ( br . s , 1h ), 6 . 83 ( dd , h a ), 6 . 34 ( s , h b ), 4 . 10 ( d , h c ), 3 . 93 ( dd , h d ), 3 . 04 ( s , 3h ), 2 . 93 ( m , h e ), 2 . 00 ( d , 3h ), 1 . 97 ( dd , h f ), 1 . 37 ( dd , h g ). ______________________________________j . sub . c , e = 0 . 0 hz j . sub . e , g = 4 . 4j . sub . c , d = 9 . 7 j . sub . f , g = 4 . 4j . sub . d , e = 4 . 7 j . sub . nh , a = 2 . 0j . sub . e , f = 7 . 7 j . sub . a , ch . sbsb . 3 = & lt ; 1 . 0______________________________________ ms : silylation with bstfa ( dmf containing 1 % tms - cl ) gave m / e m + 386 / 388 ( 22 , 12 % corresponding to product + me 3 sicl ) this compound was assayed by a standard tube dilution assay against l1210 mouse leukemia cells in culture and gave the following results : to the 4 , 5 - pyrrolo - 6 - hydroxy indoline bromide ( or mesylate ) ( 0 . 1 mmole ) in 1 ml of methylene chloride is added 0 . 1 mmole of diisopropylethyl amine and stirred under n 2 for 24 hours at room temperature . the reaction solution is taken up in 10 ml of methylene chloride , washed with 0 . 1n hcl , dried over na 2 so 4 , and concentrated to give the desired product . further purification can be accomplished by silica gel chromotography . compounds ( 11 ) and ( 12 ) exhibit antibacterial activity against b . subtilis , k . pneumonia , s . lutea , s . aureus and m . avium . ## str2 ##