compounds of the invention are of the following formulae ( i ) and ( ii ): ## str3 ## wherein r 1 is hydrogen , alkyl , or phenyl ; r 2 is hydrogen , phenyl , a thiophene ring , a furan ring , a pyrrole ring , an n - alkylpyrrole ring or phenyl independently substituted with one or more of halogen and alkyl . r 3 is hydrogen , phenyl or phenyl independently substituted with one or more of halogen , alkyl , alkoxy , or fluoroalkyl ; x is a sulfur or an oxygen atom or an nr 4 group ; and , r 4 is hydrogen , alkyl , phenyl , phenylalkyl , or phenylalkyl wherein the phenyl is independently substituted with one or more of halogen , alkyl , alkoxy , or fluoroalkyl , and the pharmaceutically acceptable acid addition salts thereof . in particular , r is hydrogen ; lower alkyl of about one to six carbon atoms ; or phenyl . r 2 , in more detail , is hydrogen ; phenyl ; 2 - or 3 - thienyl ; 2 - or 3 - furanyl ; 2 - or 3 - pyrrolo ; 2 - or 3 - pyrrolo substituted in the 1 - position with lower alkyl of about one to six carbon atoms ; or phenyl substituted by one , two or three substituents independently selected from halogen or lower alkyl of about one to six carbon atoms ; r 3 is , in more detail , hydrogen ; phenyl ; or phenyl substituted with one to three substituents independently selected from halogen , lower alkyl of about one to six carbon atoms , lower alkoxy of about one to six carbon atoms , or lower fluoroalkyl of about one to six carbon atoms . x is a sulfur or an oxygen atom or an nr 4 group . r 4 , in more detail , is hydrogen ; lower alkyl of about one to six carbon atoms ; phenyl ; phenyl lower alkyl of about one to six carbon atoms ; or phenyl loweralkyl of about one to six carbon atoms , e . g ., 1 to 3 , in the alkyl portion wherein the phenyl is substituted with one , two or three substituents independently selected from halogen , loweralkyl of about one to six carbon atoms , lower alkoxy of about one to six carbon atoms , or lower fluoroalkyl of about one to six carbon atoms . the pharmaceutically acceptable acid - addition salts of the compounds of formulae ( i ) and ( ii ) include those of a mineral or organic acid such as hydrochloric , hydrobromic , hydroiodic , sulfuric , phosphoric , fumaric , maleic , cyclohexylsulfamic , citric , lactic , methanesulfonic , and similar acids . as used herein , the terms &# 34 ; lower alkyl &# 34 ;, &# 34 ; lower alkoxy &# 34 ; and &# 34 ; lower fluoro alkyl &# 34 ; to straight or branched - chain carbon skeletons within the carbon atom limits defined . for example , &# 34 ; lower alkyl &# 34 ; defines a methyl , ethyl , propyl , i - propyl , butyl , t - butyl and the like groups . &# 34 ; lower alkoxy &# 34 ; defines methoxy , ethoxy , propoxy , i - propoxy , butoxy , t - butoxy and the like groups . &# 34 ; phenyl lower alkyl &# 34 ; defines a benzyl , phenethyl , phenpropyl , and the like groups . &# 34 ; lower fluoro alkyl &# 34 ; refers to lower alkyl groups substituted with at least one fluorine atom , such as trifluorormethyl , perfluoroethyl , 1 , 2 - difluoroethyl , 1 , 1 - difluoroethyl , 1 , 1 , 1 - trifluoroethyl and the like groups . the term &# 34 ; halo &# 34 ; ( or &# 34 ; halogen &# 34 ;) includes fluorine , chlorine , bromine , and iodine . each formula ( i ) or formula ( ii ) compound describes and comprises diastereomeric substances , themselves pairs of enantiomers . the diastereomers , isolated in their pure form , may differ in biological activity . the novel compounds of formulae ( i ) and ( ii ) constitute valuable therapeutic agents by their possession of gastric acid secretion inhibition and antidepressant activity . the various diastereomers of each formula ( i ) or formula ( ii ) compound are distinguished herein using the nomenclature system recommended by chemical abstracts for representing the relative configurations of diastereomers of fused - ring compounds , i . e ., alpha or beta nomenclature . this requires that the stereocenter corresponding to the lowest numbered atom in the ring system ( numbered according to convention ) be designated &# 34 ; alpha &# 34 ; and that the remaining stereoceter be designated &# 34 ; alpha &# 34 ; or &# 34 ; beta &# 34 ; relative to the first - assigned center . for example : ## str4 ## the compounds of formulae ( i ) and ( ii ) may be prepared by the following routes ( a ), ( b ), ( c ) and ( d ). compounds of formula ( i ) or ( ii ) wherein r 3 is hydrogen may be prepared by the ( a ) route shown above . in the first step , a substituted heterocyclic ethyl amine of formula ( iii ) is reacted with a keto acid of formula ( iv ) to form an intermediate propanoic acid of formula ( v ) or ( vi ). the propanoic acid of formula ( v ) or vi ) is then cyclized to construct a lactam of formulae ( vii ) or ( viii ), respectively . the position of the aminoethyl side - chain on the compounds of formula ( iii ) determines whether the acid formed is of formula ( v ) or ( vi ). thus , when the aminoethyl side - chain is on the 2 - position of the heterocyclic ring , the resulting acid is of formula ( v ); and , when the aminoethyl side - chain is on the 3 - position of the heterocyclic ring , the resulting lactam is of formula ( vi ). the lactams of formula ( vii ) or ( viii ) are subsequently reduced to form the compounds of the invention of formula ( i ) or ( ii ) wherein r 3 is hydrogen . more specifically , a heterocyclic 2 - or 3 - ethylamine of formula ( iii ) is condensed with levulinic acid ( or congeners thereof of formula ( iv ) in a refluxing solvent such as benzene or toluene for a period of about 2 to 5 hours to form a propanoic acid intermediate of formula ( v ) or ( vi ), respectively . the propanoic acid intermediate of formula ( v ) or ( vi ) is then cyclized to the lactam of formula ( vii ) or ( viii ), respectively , by refluxing in an inert , high - boiling solvent such as benzene , toluene , xylene or methylcellosolve under a dean - stark trap until removal of water is complete . a catalytic amount of a strong acid such as para toluenesulfonic , polyphosphoric , liquid hydrogen fluoride , pyridinium polyhydrogen fluoride and the like may be employed to aid in the cyclization step ; weaker acids such as hcl or tfa may be employed for cyclization onto a furan or pyrrole ring . alternatively , the condensation and cyclization may be carried out in one step , without isolation of the propanoic acid intermediate ( v ) or ( vi ). in this procedure , a dean - stark trap is employed throughout until water removal is complete . the lactam of formula ( vii ) or ( viii ) is subsequently reduced employing hydride reducing agents such as lithium aluminum hydride or borane - thf to yield the final products of formulae ( i ) and ( ii ), respectively . when lithium aluminum hydride is employed as the reducing agent , the reaction is preferably carried - out in an ether solvent such as , for example , diethyl ether or thf . the reaction is generally run at a temperature range from about ambient to about the refluxing temperature of the mixture . the reaction time varies from about four hours to about two days , depending on the temperature conditions employed and the reactivity of the substrate towards the reducing agent . when borane - thf is the reducing agent , the reaction is generally carried out in refluxing thf for a period of about 1 . 5 - 2 hours . compounds of formula ( i ) or ( ii ) wherein r 3 is hydrogen may also be prepared by the ( b ) route shown above . in the first step , a substituted heterocyclic ethylamine of forumula ( iii ) is reacted with an alpha - angelicalactone ( or congeners thereof ) of formula ( ix ) to form an intermediate amido ketone of formula ( x ). the position of the aminoethyl side - chain on the compounds of formula ( iii ) determines the position of the amidoketone side - chain on the compounds of formula ( x ) and subsequently the lactam structure ( vii ) or ( viii ). thus , when the aminoethyl side - chain is on the 2 - position of the heterocyclic ring , the resulting lactam is of formula ( vii ); and , when the aminoethyl side - chain is on the 3 - position of the heterocyclic ring , the resulting lactam is of formula ( viii ). the lactams of forumla ( vii ) or formula ( viii ) are subsequently reduced as described in route ( a ) to form the compounds of the invention of formula ( i ) or ( ii ) wherein r 3 is hydrogen . more specifically , a heterocyclic ethylamine of formula ( iii ) is condensed with the alpha - angelicalactone in a refluxing solvent such as toluene , thf or methylene chloride for about one to six hours to form a keto - amide of formula ( x ). the keto - amide is then cyclized by heating in a solvent such as absolute ethanol or toluene in the presence of a strong acid such as hydrogen chloride , methane sulfonic or trifluoroacetic acid for a period of about two to eight hours to yield a lactam of formula ( vii ) or ( viii ). in the last step of this method , the lactam is reduced as described for route ( a ) to yield the final products of formulae ( i ) and ( ii ), respectively , wherein r 3 is hydrogen . the imide , acyliminium route ( c ) yields compounds of formula ( i ) or formula ( ii ) wherein r is hydrogen . an ethylamine of formula ( iii ) is first reacted in two steps with succinic anhydride ( or congeners thereof ) to form an imide of formula ( xi ). the imide is then reduced with sodium borohydride in ethanol in the presence of excess methanesulfonic acid as described by speckamp , et al . in tetrahedron , vol . 31 , page 1437 ( 1975 ) to form an ethoxy species of formula ( xii ). cyclization of ( xii ) in the presence of a strong acid yields a lactam of formula ( vii ) or ( viii ). in the case of furan and pyrrole compounds of formula ( xi ), cyclization may take place simultaneously under the conditions described for the sodium borohydride reduction . more particularly , a heterocyclic ethylamine of formula ( iii ) is treated with a solution of succinic anhydride in an inert solvent such as thf or methylene chloride followed by removal of the solvent and heating of the resulting residue ( an amide - acid intermediate ; structure not shown ) at a temperature of about 130 ° c . to about 180 ° c . to yield an imide of formula ( xi ). the imide is next treated with ethanol and sodium borohydride at a temperature of about - 5 ° c . to 5 ° c . followed by dropwise addition of excess 2n methane sulfonic acid in ethanol over a period of about three to six hours so that the final ph is about 1 to 3 . the temperature is allowed to warm to ambient while stirring for an additional eight to twenty - four hours to yield an ethoxy intermediate of formula ( xii ). the ethoxy intermediate is cyclized by reacting at a temperature of about 25 ° c . to 110 ° c . in an inert solvent such as ethanol or toluene in the presence of an anhydrous strong acid such as hydrogen chloride , methane sulfonic or trifluoroacetic acid for a period of about two to five hours to yield a lactam of formula ( vii ) or ( viii ). the lactam is then reduced as described for route ( a ) to yield the final products of formula ( i ) or ( ii ), respectively , wherein r 1 is hydrogen . compounds of formulae ( i ) or ( ii ) wherein r 3 is other than hydrogen , particularly wherein r 3 is phenyl or substituted phenyl , are prepared by reaction of a lactam of formula ( vii ) or ( viii ) with phenyl lithium or a substituted phenyl lithium derivative to form an intermediate substituted tetrahydroindolizine of formulae ( xiii ) or ( xiv ), followed by reduction . in the case where a substituted phenyllithium is used , the substituted phenyllithium may be prepared by transmetallation of an appropriately substituted phenyl compound with butyllithium by methods well - known in organic chemistry . ## str8 ## in particular , a compound of formulae ( vii ) or ( viii ) in an inert anhydrous solvent such as anhydrous thf or diethyl ether is treated with a solution of phenyllithium or a substituted phenyllithium in an inert solvent such as ether at a temperature of about 5 ° c . to about the reflux temperature of the solvent to form an intermediate tetrahydroindolizine of formulae ( xiii ) or ( xiv ). the alkene is subsequently reduced by the action of a solution of lialh 2 cl 2 ( freshly prepared from equimolar amounts of lah and anhydrous aluminum chloride ) in a dry inert solvent such as anhydrous diethyl ether . the reaction mixture is stirred for a period of about 1 to 150 hours at a temperature of about 0 ° to 50 ° c . to yield the products of formulae ( i ) and ( ii ) in their free base form . the cyclization reactions in routes ( a )-( c ) afford mixture of diastereomers . in certain instances , product mixture may be highly enriched in specific diastereomers . the diastereomers may be separated and purified by standard techniques known to those skilled in the art of organic chemistry , such as fractional crystallization or liquid chromatography of free bases , or fractional crystallization of acid - addition salts . diastereomers may be interconverted by treatment with a base . specifically , heating of lactam diastereomers of formulae ( vii ) or ( viii ) wherein r 1 and / or r 2 are hydrogen atoms in aqueous dmso at a temperature of about 100 ° to 150 ° c . in the presence of an alkali metal carbonate , such as k 2 co 3 , for a period of about 40 minutes to three days gives rise to equilibrium mixtures of diastereomers . similarly , heating of the amine diastereomers of formulae ( i ) or ( ii ) wherein r 1 and / or r 2 are hydrogen atoms in aqueous dmso at about 80 ° to 150 ° c . in the presence of an alkali metal hydroxide such as naoh for a period of about 1 to 120 hours , can give rise to equilibrium mixtures of diastereomers . such equilibration methods can enhance the proportions of minor diastereomers in comparison to the original product mixtures from cyclization . in appropriate instances , the equilibration method can alter relative configuration between the stereocenters involved . because the subject compounds of formula ( i ) and ( ii ) possess a basic nitrogen atom , they may be converted into the corresponding acid addition salts . the acid addition salts may be prepared by reaction with an appropriate acid , as for example , an inorganic acid such as a hydrohalic acid , i . e ., hydrochloric , hydrobromic or hydroiodic acid ; sulfuric or nitric acid ; phosphoric acid ; an organic acid such as acetic , propionic , glycolic , pamoic , pyruvic , malonic , succinic , maleic , picric , fumaric , malic , tartaric , citric , benzoic , cinnamic , mandelic , methanesulfonic , ethanesulfonic , benzenesulfonic , p - toluenesulfonic , salicylic , 2 - naphthalenesulfonic or p - aminosalicylic acid . the therapeutically active , nontoxic acid addition salts of subject compounds of formula ( i ) and ( ii ) are included within the scope of the present invention . in addition to the novel compounds of formulae ( i ) and ( ii ), novel intermediates of formulae ( v ), ( vi ), ( vii ), ( viii ), ( xiii ) and ( xiv ) are included in this invention as being useful as intermediates in the preparation of the active compounds of formulae ( i ) and ( ii ). when these intermediates possess a basic center and / or an acidic center , the acid addition salts and base addition salts thereof are also included within the scope of the invention . the compounds of the invention are useful for inhibition of gastric acid secretion as measured by the following test . female sprague - dawley rats are fasted twenty - four hours before testing and are given water ad libidum while being kept in individual cages . on the day of testing , the rats are weighed and are selected so that the rats in each test weigh within a range of ± 20 grams . surgery is carried out under light ether anesthesia . as soon as the rat is anesthetized its teeth are removed and a mid - line incision is made on the abdomen about 11 / 2 inches in length and the stomach and duodenum are exposed . if at this point the stomach is filled with food or fecal material , the rat is not used . if the condition of the stomach is acceptable , a purse string stitch is placed on the fundic portion of the stomach with a suture , taking care not to pierce any blood vessels in the area . a small nick is then made into the stomach in the center of the purse string , and a cannula , consisting of a small vinyl tube with a flange on one end , is put into the stomach , and the purse string stitch is closed tightly around the flange . the test compound is administered intraduodonally ( i . d .) immediately after surgery in a volume of 0 . 5 ml / 100 grams rat . control rats receive the test vehicle , 0 . 5 % aqueous methyl cellulose . after the surgery and after administration of the test compound , the abdominal wall and skin are closed simultaneously with three or four 10 mm wound clips and a collecting tube is placed on the cannula . each rat is then placed in a box in which a longitudinal slit has been made to allow the cannula to hang freely and to allow the rat to move about unencumbered . after the rat has been allowed to stabilize for thirty minutes , the collection tube on the cannula is discarded and replaced with a clean tube to receive the gastric juice . collections are made at one hour . the sample of gastric contents collected is drained into a centrifuge tube and centrifuged to pack down the sediment . the volume is read and a 1 ml aliquot of the supernatant is put into a beaker containing 10 ml distilled water and is titrated to ph 7 using 0 . 01 n sodium hydroxide . results are determined for volume , titratable acid and total acid output , where volume equals total ml of gastric juice minus sediment ; titratable acid ( meq / 1 ) equals amount of 0 . 01 n sodium hydroxide needed to titrate the acid to ph 7 ; and total acid output equals titratable acid times volume . results are reported as % inhibition of total acid output ( tao ) for a dose of 20 mg / kg i . d . of the compound of formula ( i ) or ( ii ). particularly useful are compounds having significant inhibition of tao at a dose of 20 mg / kg . it is well - known that excessive secretion of gastric hydrochloric acid leads to unneeded peptic activity and endangers the mucous lining of the duodenum . the use of gastric antisecretory agents is thus desirable as an aid in the prevention and amelioration of distress occasioned by high concentration of stomach acid . the pharmacological effect of the compounds of the present invention as inhibitors of gastric acid secretion , is shown in table i below . table i______________________________________acute gastric fistula rat screencompound of % inhibition of taoexample no . @ 20 mg / kg i . d . ______________________________________4 785 667 8610 8212 3713 7416 8617 ( 1st ) 9017 ( 2nd ) 8818 10019 ( 1st ) 9819 ( 2nd ) 9819 ( 3rd ) 8820 ( 1st ) 4720 ( 2nd ) 41______________________________________ in addition to their utility in the treatment of excessive gastric acid secretion , compounds of formulae ( i ) and ( ii ) exhibit useful biological activity in the central nervous system . more particularly , they exhibit antidepressant activity in warm - blooded animals . the central nervous system utility of the novel compounds of this invention is based on a standard test for antidepressant agents involving antagonism of the depressant effects of tetrabenazine ( tbz ). this is the &# 34 ; classical &# 34 ; tetrabenazine antagonism assay described in u . s . pat . no . 3 , 787 , 577 . mice are injected with a test compound 30 minutes prior to the injection of 32 mg / kg i . p . of tbz , a drug which decreases normal exploratory activity and induces ptosis . after 30 minutes , the mice are tested for two parameters : the presence of normal exploratory activity ( ea ) and reversal of ptosis ( pt ). a control group of mice is given only 32 mg / kg i . p . of tbz . the biological activity of the novel compounds of this invention compared to imipramine may be understood by some representative , nonlimiting examples , presented in table ii . table ii______________________________________tetrabenzine antagonism assaycompound of tbz ed . sub . 50 ea / ptex . no . mg / kg ( i . p . ) ______________________________________17 ( 2nd ) 2 . 4 / ca . 0 . 7520 ( 2nd ) ca . 24 / ca . 30imipramine 1 . 2 / 0 . 5______________________________________ in view of the antisecretory activity of the subject compounds of formulae ( i ) and ( ii ), there is further provided herein a method of inhibiting gastric acid secretion which comprises internally administering to a gastric hyperacidic subject ( man or animal ) an effective gastric acid secretion inhibiting amount of a compound of formula ( i ) or ( ii ), in base or acid addition salt form , preferably in admixture with a pharmaceutically acceptable carrier . pharmaceutical compositions comprising a subject compound ( i ) or ( ii ) are also considered a further aspect of the present invention . additionally , in view of the antidepressant activity of the subject compounds of formula ( i ) and ( ii ), there is further provided herein a method of treating depression which comprises internally administering to a depressed subject ( particularly a human subject ) an effective antidepressant amount of a compound of formula ( i ) or ( ii ) in base or acid addition salt form , preferably in admixture with a pharmaceutically - acceptable , non - toxic carrier . for the treatment of excess gastric acid secretion or depression , compounds of the present invention of the formula ( i ) or ( ii ) may be administered orally or parenterally in a pharmaceutical composition comprising about 10 to 4000 mg , preferably about 20 to 2000 mg of one or more of the subject compounds per day for an average adult human depending on the activity of the particular compound chosen . the dosage may be divided into 1 to 4 unit dosage forms per day . while the therapeutic methods of the invention are most useful for human subjects in need of alleviation of excess gastric acid secretion or depression , the compounds may be administered to other mammals at comparable dosages per weight of the subject . to prepare the pharmaceutical compositions of this invention , one or more compounds or salt thereof of the invention as the active ingredient , is intimately admixed with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques , which carrier may take a wide variety of forms depending on the form of preparation desired for administration , e . g ., oral or parenteral . in preparing the compositions in oral dosage form , any of the usual pharmaceutical media may be employed . thus , for liquid oral preparations , such as for example , suspensions , elixirs and solutions , suitable carriers and additives include water , glycols , oils , alcohols , flavoring agents , preservatives , coloring agents and the like ; for solid oral preparations such as , for example , powders , capsules and tablets , suitable carriers and additives include starches , sugars , diluents , granulating agents , lubricants , binders , disintegrating agents and the like . because of their ease in administration , tablets and capsules represent the most advantageous oral dosage unit form , in which case solid pharmaceutical carriers are obviously employed . if desired , tablets may be sugar coated or enteric coated by standard techniques . for parenterals , the carrier will usually comprise sterile water , though other ingredients , for example , for purposes such as aiding solubility or for preservation , may be included . injectable suspensions may also be prepared , in which case appropriate liquid carriers , suspending agents and the like may be employed . more particularly , a pharmaceutical composition useful for inhibiting gastric acid secretion will contain per unit dosage from about 5 to about 1000 mg of the active ingredient , and , preferably , from about 10 to about 400 mg . a pharmaceutical composition useful for treating depression will contain per unit dosage from about 5 to about 500 mg of the active ingredient , and , preferably , from about 5 to about 250 mg . the total daily dosage may be divided into 1 to 4 unit dosage forms per day . the following examples are intended to illustrate but not to limit the scope of the present invention . in the following examples and throughout the specification , the following abbreviations may be used : mg ( milligrams ); g ( grams ); kg ( kilograms ); mm ( millimeters ); l ( liters ); mmole ( millimoles ); m ( molar ); n ( normal ); psi ( pounds per square inch ); mp ( melting point ); bp ( boiling point ); dec ( decomposes ); meq ( milliequivalents ); e ( trans ); z ( cis ); et 2 o ( diethyl ether ); etoac ( ethyl acetate ); meoh ( methanol ); etoh ( ethanol ); i - proh ( isopropanol ); lah ( lithium aluminum hydride ); tfa ( trifluoroacetic acid ); dmso ( dimethylsulfoxide ); thf ( tetrahydrofuran ); dmf ( dimethylformamide ); i . p . ( intraperitoneal ); tao ( total acid output ); hplc ( high pressure liquid chromatography ); and c , h , n , o , etc . ( the chemical symbols for the elements ). unless otherwise indicated , all temperatures are reported in ° c . ( degrees centigrade ). to a solution of 81 . 6 g ( 0 . 704 mole ) of levulinic acid in 1 . 5 liters of benzene was added 70 . 4 g ( 0 . 64 mole ) of 2 -( 2 - aminoethyl ) pyrrole in 1 liter of benzene . the solution was heated at reflux for 41 / 2 hours with the azeotropic removal of water . the mixture was cooled , and the precipitate collected and air dried to give 106 g of a gray solid which was crystallized from ethanol / water to give the title compound , a white solid , mp 206 °- 210 ° ( dec ). a solution of 95 . 4 ( 0 . 46 mole ) of 4 , 5 , 6 , 7 - tetrahydro - 4 - methyl - 1h - pyrrolo [ 3 , 2 - c ] pyridine - 4 - propanoic acid , the product of example 1 , in 2 liters of methyl cellosolve was heated at reflux for four hours . the solvent was evaporated at reduced pressure , and the residue washed twice with benzene . the benzene extracts were washed successively with 1n hydrochloric acid , aqueous sodium bicarbonate , and brine , then dried over anhydrous magnesium sulfate and evaporated at reduced pressure to give 9 . 8 g ( 11 %) of the title compound , a tan solid , mp 185 °- 188 ° c . to a suspension of 5 . 5 ml of 35 % potassium hydride in oil under nitrogen was added 70 ml of dry dimethylsulfoxide . a solution of 7 . 1 g of 4 , 5 , 7 , 8 , 9 , 9a - hexahydro - 9a - methyl - 3h - pyrrolo [ 2 , 3 - g ] indolizin - 7 - one , the product of example 2 , in 60 ml of dry dimethylsulfoxide was added with cooling . the resulting mixture was stirred at room temperature for 11 / 2 hours . a solution of 5 . 96 g ( 0 . 037 mole ) of alpha , 2 - dichlorotoluene in 30 ml of dry dimethylsulfoxide was added and stirring continued for three hours . the mixture was then heated at 55 ° c . for one hour and allowed to stir at room temperature overnight . the reaction mixture was extracted three times with hexane , then poured into 550 ml of water . the aqueous layer was extracted with methylene chloride . the combined extracts were washed with brine , dried over anhydrous magnesium sulfate , and evaporated to give 10 . 5 g ( 90 %) of title compound , a dark oil . a solution of 12 . 5 g of 3 -( 2 - chlorobenzyl )- 4 , 5 , 7 , 8 , 9 , 9a - hexahydro - 9a - methyl - 3h - pyrrolo [ 2 , 3 - g ] indolizin - 7 - one , the product of example 3 , in 300 ml of ether was added under nitrogen to a slurry of 3 . 8 g ( 0 . 1 mole ) of lah in 50 ml of ether . this mixture was stirred at room temperature overnight then heated at reflux for five hours . excess hydride was destroyed with 3 . 8 ml of water , 3 . 8 ml of 10 % aqueous sodium hydroxide , and 10 ml of water . the white precipitate was removed by filtration and washed well with ether . the filtrate was evaporated in vacuo to obtain a yellow oil which was distilled at 140 ° c . and 0 . 025 torr to give 6 . 42 g of an oil . this oil was taken up in an equal volume of methylcyclohexane and crystallized to give 3 . 4 g ( 28 %) of the title compound , a tan solid , mp 58 °- 61 ° c . elemental analysis : calculated for c 18 h 21 cln 2 : c , 71 . 87 ; h , 7 . 04 . found : c , 71 . 65 ; h , 7 . 10 . a slurry of 3 . 04 g ( 0 . 08 mole ) of lah in 40 ml of dry thf under argon was treated with a solution of 6 . 17 g ( 0 . 032 mole ) of 4 , 5 , 7 , 8 , 9 , 9a - hexahydro - 9a - methyl - 3h - pyrrolo [ 2 , 3 - g ] indolizin - 7 - one , the product of example 2 , in 120 ml of thf over a period of 15 minutes . the mixture was stirred overnight at room temperature , then heated at reflux for four hours . the excess hydride was decomposed with 3 ml of water , 3 ml of 10 % sodium hydroxide , and 7 ml of water . the resulting white precipitate was filtered off and washed several times with thf . the combined filtrate and washings were evaporated at reduced pressure to give 5 . 1 g of an oil . this material was taken up in hot i - proh and added to a solution of 2 . 09 g of fumaric acid in hot i - proh . the fumarate salt was recrystallized from i - proh to give 2 . 85 g ( 31 % yield ) of title compound , mp 173 °- 175 ° ( dec ). elemental analysis : calculated for c 15 h 20 n 2 o 4 : c , 61 . 24 ; h , 6 . 97 . found : c , 61 . 24 ; n , 6 . 96 . a suspension of 16 g ( 0 . 129 mole ) of 2 -( 2 - aminoethyl )- 1 - methylpyrrole and 25 . 3 g ( 0 . 142 mole ) of 3 - benzoylpropionic acid in 600 ml of xylene was refluxed with a dean - stark trap until 4 . 2 ml of water had been collected . the xylene was evaporated in vacuo , the residue dissolved in methylene chloride and washed successively with dilute hydrochloric acid , 5 % sodium bicarbonate solution , and brine . the methylene chloride layer was dried over anhydrous magnesium sulfate and evaporated in vacuo to give 29 . 9 g of residue which was chromatographed on silica gel and eluted with petroleum ether . fractions enriched with product were combined , and evaporated in vacuo to give a brownish yellow oil which crystallized from cyclohexane to give 6 . 3 g of a yellow solid , mp 130 °- 133 ° c . this material was recrystallized from methanol to give 2 . 7 g of title compound , mp 133 °- 135 ° c . a solution of 5 . 95 g ( 0 . 0224 mole ) of 4 , 5 , 7 , 8 , 9 , 9a - hexahydro - 3 - methyl - 9a - phenyl - 3h - pyrrolo [ 2 , 3 - g ] indolizin - 7 - one , the compound of example 6 , in 400 ml of ether was added to a suspension of 1 . 71 g ( 0 . 0448 mole ) of lah in 35 ml of ether under argon . the mixture was stirred at ambient temperature overnight . after the addition of water and 10 % sodium hydroxide solution , the resulting white precipitate was filtered off and the filtrate evaporated in vacuo to give 5 . 5 g of a light green oil . the oil was crystallized from methanol to give 3 . 3 g ( 61 %) of the title compound , a white solid , mp 71 °- 73 ° c . elemental analysis : calculated for c 17 h 20 n 2 : c , 80 . 91 ; h , 7 . 99 ; n , 11 . 10 . found : c , 81 . 09 ; n , 7 . 67 ; n , 11 . 05 . a mixture of 175 g ( 0 . 87 mole ) of 2 , 5 - dimethoxytetrahydro - 2 - furaldedimethylacetal and 81 g ( 0 . 87 mole ) of aniline in 400 ml of glacial acetic acid was heated at reflux for 30 minutes , then the solvent was evaporated at reduced pressure . the residue was taken up in 240 ml of dioxane , 87 ml of 0 . 5n hydrochloric acid added , and the mixture heated at reflux for five minutes , cooled , poured into one liter of water and extracted five times with ether . the combined ether extracts were washed with water , sodium bicarbonate solution , and brine , then dried over anhydrous magnesium sulfate . the water wash was extracted three times with ether . the combined ether extracts were washed and dried as above . the two ether solutions were combined and evaporated at reduced pressure to give 160 g of a dark oil . the oil was taken up in ether , and chromatographed on neutral alumina , eluting with ether . a dark oil was obtained ( 134 . 3 g ), which was crude n - phenylpyrrole - 2 - carboxaldehyde . a solution of 134 . 3 g ( 0 . 785 mole ) of the crude aldehyde in 225 ml of absolute ethanol , 13 . 6 ml of n - benzylamine , 10 ml of glacial acetic acid , and 54 ml ( 0 . 785 mole ) nitromethane was stirred at about 40 ° c . for 1 . 5 hrs . on cooling , a dark precipitate formed and was collected by filtration to give 111 . 4 g of dark brown solid . an ethereal solution of this solid was filtered through dicalite and evaporated at reduced pressure to give 110 . 6 g ( 66 %) of a dark solid , mp 86 °- 89 ° c ., which was 1 - nitro - 2 -( 1 - phenylpyrrol - 2 - yl ) ethene . a slurry of 79 g ( 2 . 08 moles ) of lah in 800 ml of thf was treated slowly with a solution of 110 . 6 g ( 0 . 52 mole ) of the nitro compound in 450 ml of thf . this mixture was heated at reflux for eight hours and stirred at room temperature for 36 hours . excess hydride was decomposed by very careful addition of 79 ml of water , 79 ml of 10 % sodium hydroxide and 79 ml of water . the resulting light tan precipitate was collected by filtration and washed well with thf . the filtrate was evaporated at reduced pressure to afford 89 . 5 g of dark brown oil . the oil was distilled at 94 °- 97 ° c ./ 0 . 1 torr to give 57 g of free base , a colorless oil . a solution of 7 . 0 g ( 0 . 038 mole ) of this oil in 20 ml of hot i - proh was treated with a solution of 2 . 18 g ( 0 . 019 mole ) of fumaric acid in 50 ml of hot i - proh . on cooling , the white precipitate was collected by filtration and recrystallized from absolute ethanol to give the title compound , mp 169 °- 170 . 5 ° c . a solution of 34 . 4 g ( 0 . 296 mole ) of levulinic acid in 625 ml of toluene was added to a solution of 50 g ( 0 . 269 mole ) of 2 -( 1 - phenylpyrrol - 2 - yl ) ethylamine , the free base of example 8 . the mixture was heated at reflux for four hours and 9 . 4 ml of water was collected in a dean - stark trap . when the heat source was removed , the clear orange solution turned red . another 800 ml of toluene were added and the solution was washed twice with 1n hydrochloric acid , twice with aqueous sodium bicarbonate , once with water , then brine , dried over anhydrous magnesium sulfate and evaporated at reduced pressure to obtain 74 . 3 g of a brown oil . the oil was crystallized from 350 ml of i - proh to obtain 41 . 9 g of a tan solid . concentration of the mother liquor gave another 4 . 9 g . one recrystallization from i - proh gave pure title compound , mp 145 °- 147 . 5 ° c . to a suspension of 5 . 2 g ( 0 . 14 mole ) of lah in 450 ml of ether under nitrogen was added 14 . 7 g ( 0 . 055 mole ) of 4 , 5 , 7 , 8 , 9 , 9a - hexahydro - 9a - methyl - 3 - phenyl - 3h - pyrrolo -[ 2 , 3 - g ] indolizin - 7 - one , the compound of example 9 . the mixture was stirred at ambient temperature for two days . excess hydride was decomposed by careful addition of 5 . 2 ml of water , 5 . 2 ml of 10 % sodium hydroxide and 5 . 2 ml of water . the white precipitate was collected by filtration and washed well with ether . the filtrate was evaporated in vacuo to obtain 14 . 5 g of a white solid . recrystallization from 200 ml of hexane afforded 12 . 1 g ( 87 %) of the title compound , mp 111 °- 113 ° c . elemental analysis : calculated for c 17 h 20 n 2 : c , 80 . 91 ; h , 7 . 99 . found : c , 80 . 78 ; h , 7 . 91 . a stirred solution of 76 . 5 g ( 0 . 66 mole ) of levulinic acid in 1 . 1 liters of benzene was treated with a solution of 74 . 8 g ( 0 . 6 mole ) of 2 -( 2 - aminoethyl )- 1 - methylpyrrole in 550 ml of benzene and refluxed for 4 . 5 hours . a solution of 0 . 5 g of p - toluenesulfonic acid in 40 ml of benzene was added and the mixture refluxed for two more hours with azeotropic removal of water . the reaction was cooled , 250 ml of 1n hydrochloric acid added and the organic layer was washed two more times with 1n hydrochloric acid . the benzene solution was washed with sodium bicarbonate solution , brine , dried over anhydrous magnesium sulfate and evaporated in vacuo to yield 95 . 5 g of a brown solid . recrystallization from cyclohexane gave 85 g ( 69 %) of the title compound , a tan solid , mp 103 °- 106 ° c . to a stirred solution of 36 . 3 g ( 0 . 19 mole ) of 4 - bromochlorobenzene in 100 ml of dry ether under nitrogen was added with cooling 137 ml of a 0 . 39m hexane solution of n - butyllithium . stirring was continued at room temperature for two hours . this mixture was added under nitrogen to a vigorously stirred suspension of 35 g ( 0 . 17 mole ) of 3 , 9a - dimethyl - 4 , 5 , 7 , 8 , 9 , 9a - hexahydro - 3h - pyrrolo [ 2 , 3 - g ] indolizin - 7 - one , the compound from example 11 , in 800 ml of dry ether in a morton flask . the resulting brown suspension was stirred overnight at room temperature . the reaction mixture was poured into 300 ml of 1n phosphoric acid and 400 ml of ice water , stirred for ten minutes , then basified with 50 % aqueous sodium hydroxide . the aqueous layer was separated and extracted twice with methylene chloride . the combined organic extracts were washed with water , then brine , dried over anhydrous sodium sulfate and evaporated at reduced pressure to obtain a dark viscous residue . crystallization from methanol gave 20 . 3 g ( 40 %) of an orange - brown solid which was 7 -( 4 - chlorophenyl )- 4 , 5 , 9 , 9a - tetrahydro - 3 , 9a - dimethyl - 3h - pyrrolo [ 2 , 3 - g ] indolizine , mp 143 °- 148 ° dec . a solution of 6 . 27 g ( 0 . 047 mole ) of aluminum trichloride in 100 ml of dry ether was added in one portion to 36 . 2 ml of 1 . 3m ethereal solution of lah and stirred at room temperature for 45 minutes . to the resulting mixture was added 28 . 9 g of 7 -( 4 - chlorophenyl )- 4 , 5 , 9 , 9a - tetrahydro - 3 , 9a - dimethyl - 3h - pyrrolo [ 2 , 3 - g ] indolizine as prepared above over a period of ten minutes . the tan suspension was stirred for six days . excess hydride was destroyed by addition of 15 ml of 10 % aqueous sodium hydroxide , and the reaction mixture poured into 150 ml of 1n sodium hydroxide followed by filtration through filter aid . the aqueous layer was separated and extracted with ether . the combined ether extracts were washed twice with water , once with brine , dried over anhydrous potassium carbonate and evaporated at reduced pressure to yield 11 . 2 g of brown residue , an oil . a solution of 3 . 5 g of fumaric acid in hot i - proh was added to a solution of 9 . 2 g of the oil in i - proh . after cooling , 8 . 0 g of brown solid was collected . recrystallization once from i - proh , and once from water gave 1 . 6 g of the title compound a tan solid , mp 185 °- 188 ° ( dec .). elemental analysis : calculated for c 18 h 21 n 2 cl . 0 . 7c 4 h 4 o 4 . 0 . 2h 2 o : c , 64 . 78 ; h , 6 . 32 . found : c , 64 . 79 ; h , 6 . 28 . a solution of 2 . 04 g ( 0 . 01 mole ) of 3 , 9a - dimethyl - 4 , 5 , 7 , 8 , 9 , 9a - hexahydro - 3h - pyrrolo [ 2 , 3 - g ] indolizin - 7 - one , the compound of example 11 , in 70 ml of ether was added to 0 . 76 g ( 0 . 02 mole ) of lah in 15 ml of ether under argon and allowed to stir overnight . water ( 1 . 5 ml ) and 25 % sodium hydroxide ( 0 . 75 ml ) were added and the mixture stirred for two hours . the solids were filtered and washed with ether . ethereal hydrogen chloride was added to the ether filtrate and the salt filtered . recrystallization from i - proh yielded 1 . 8 g ( 80 %) of the title compound , mp 279 °- 281 ° ( dec ). elemental analysis : calculated for c 13 h 18 cln 2 : c , 63 . 56 ; h , 8 . 45 . found : c , 63 . 42 ; h , 8 . 52 . a solution of 14 . 7 g of 1 - nitro - 2 -( 1 - methylpyrrol - 3 - yl ) ethylene prepared by the method shown in u . s . pat . no . 4 , 002 , 643 , example xv in 250 ml of thf was added to a suspension of 11 . 8 g of lah in 250 ml of ether at a rate that the mixture refluxed gently . it was heated under reflux for five hours . water ( 12 ml ), then 12 ml of 10 % sodium hydroxide solution , and finally 36 ml of water were added to decompose the excess hydride . the solid was filtered , and washed with thf . the filtrate was evaporated to give 12 g of a yellow oil which was taken up in acetonitrile and 17 . 4 g ( 0 . 11 mole ) of cyclohexanesulfamic acid added . the cyclohexanesulfamate salt was collected to give 22 g ( 74 %) of the title compound , mp 153 °- 155 ° c . a mixture of 6 . 8 g of 3 -( 2 - aminoethyl )- 1 - methylpyrrole obtained from the cyclohexanesulfamate salt as prepared in example 14 and 6 . 4 g of levulinic acid in 150 ml of benzene was heated to reflux for 2 . 5 hours . the solution was washed with water , dried over anhydrous magnesium sulfate , and evaporated under reduced pressure to yield 8 . 0 g of a yellow solid . recrystallization from ethyl acetate / methylcyclohexane , then from i - proh yielded 6 . 0 g ( 60 %) of the title compound , mp 120 °- 122 ° c . a solution of 5 . 1 g of 1 , 9a - dimethyl - 4 , 5 , 7 , 8 , 9 , 9a - hexahydro - 1h - pyrrolo -[ 3 , 2 - g ] indolizin - 7 - one , the compound of example 15 , in 50 ml of thf was added dropwise to a suspension of 2 . 38 g of lah in 100 ml of ether and stirred overnight at ambient temperature . after the addition of 2 . 4 ml of water , 2 . 4 ml of 10 % sodium hydroxide , and 7 . 0 ml of water , the solid was filtered and washed with thf . the filtrate was dried over anhydrous potassium carbonate and evaporated under reduced pressure to give 5 . 0 g of clear oil . the oil was dissolved in benzene and 4 . 5 g of cyclohexanesulfamic acid in benzene was added . the resulting salt was filtered and recrystallized from benzene to yield 6 . 1 g ( 66 %) of the title compound , mp 117 °- 118 ° c . elemental analysis : calculated for c 18 h 31 n 3 o 3 s : c , 58 . 50 ; h , 8 . 45 . found : c , 58 . 44 ; h , 8 . 48 . n - methylpyrrole ( 54 . 3 g , 0 . 67 mole ) and ω - nitrostyrene ( 50 . 0 g , 0 . 34 mole ) were combined in 115 ml of glyme and 270 ml of dilute h 2 so 3 ( ph = 3 ). the solution was maintained at 80 ° c . for eight hours , cooled , diluted with 200 ml of water , and extracted wth methylene chloride . the organic layer was washed once with water , once with saturated nahco 3 solution , and once with saturated nacl . the solution was dried ( k 2 co 3 ) and evaporated in vacuo to a brown solid ( 77 . 7 g ). the solid was recrystallized from methanol ( 140 ml ) to give a tan crystalline nitroethane product ( 40 . 5 g , 52 %; mp of a sample recrystallized from methanol , 83 °- 85 ° c .). this material ( 36 . 3 g , 0 . 158 mole ) in 500 ml of ether was reduced with lah ( 17 . 39 g , 0 . 474 mole ) in 300 ml of ether at room temperature . after 18 hours , 18 ml of water was added dropwise , followed by 18 ml of 15 % naoh , and 54 ml of water . the precipitate was filtered and the ether layer was separated , dried ( k 2 co 3 ) and evaporated in vacuo to give an orange solid ( 22 . 9 g , 73 %) which was 2 -[ 2 -( 1 - methylpyrrol )] phenethylamine . this amine ( 21 . 7 g , 0 . 108 mole ) in 150 ml of dry thf was added slowly to succinic anhydride ( 10 . 9 g , 0 . 109 mole ) in 100 ml of thf . the solution was evaporated to an oil , which was heated at 175 ° c . for five hours . the oil was cooled , dissolved in methylene chloride and washed once with 1n hcl , once with 1n naoh , once with water , once with brine , dried ( mgso 4 ) and evaporated in vacuo to a brown oil ( 31 . 0 g ), an imide . the imide ( 31 . 0 g ) was dissolved in 250 ml of methylene chloride and 250 ml of ethanol cooled to 0 ° c . and combined with nabh 4 ( 18 . 3 g ). methanesulfonic acid ( 10 drops ) was added and the temperature was maintained at 0 ° c . while every 15 minutes ten drops of a 2n methanesulfonic acid in ethanol was added over the next six hours . additional acid was added more quickly at 0 ° c . until adjusted to ph 1 and then the mixture was stirred at room temperature for 16 hours . the reaction was partitioned between methylene chloride and water and the organic solution was washed twice with water , once with brine , dried ( k 2 co 3 ) and evaporated in vacuo to give oily lactams ( 28 . 4 g ). this was combined with 225 ml of dmso , 10 ml of water and k 2 co 3 ( 75 g ) and refluxed under nitrogen for 3 . 5 hours . the resulting solution was cooled , evaporated in vacuo to half volume and partitioned between chloroform and water . the organic phase was washed twice with water , once with brine , dried ( k 2 co 3 ) and evaporated in vacuo to give the lactams in a 70 / 30 ratio of alpha / beta isomers . this mixture in 40 ml of dry thf was added to 300 ml of 1m bh 3 . thf solution at 0 ° c . and refluxed under n 2 for one hour . the solution was cooled , 60 ml of water cautiously added followed by 90 ml of 12n hcl and the thf was removed by distillation . the residual aqueous solution was refluxed for 20 minutes , cooled and treated with 10 % naoh to ph 11 . the solution was extracted with methylene chloride , which was separated and washed twice with water , once with brine , dried ( k 2 co 3 ) and evaporated in vacuo to give 23 . 9 g of crude amines . the amines were separated by preparative hplc on silica gel using methylene chloride / methanol ( 10 : 1 ) to give two products : 4 , 5 , 7 , 8 , 9 , 9a - alpha - hexahydro - 3 - methyl - 4 - alpha - phenyl - 3h - pyrrolo [ 2 , 3 - g ] indolizine which was converted to its hbr salt in i - proh and recrystallized from i - proh to give 6 . 0 g of white crystals , mp 194 °- 195 ° c . similarly , the 4 , 5 , 7 , 8 , 9 , 9a - beta - hexahydro - 3 - methyl - 4 - alpha - phenyl - 3h - pyrrolo [ 2 , 3 - g ] indolizine isomer ( 4 . 6 g ) was converted to its hbr salt and recrystallized from i - proh to give 1 . 7 g of white crystals , mp 203 °- 204 ° c . elemental analysis : calculated for ( alpha ) c 17 h 20 n 2 . hbr . 1 / 12c 3 h 8 o : c , 61 . 25 ; h , 6 . 46 ; n , 8 . 28 . found : c , 61 . 35 ; h , 6 . 41 ; n , 8 . 40 . calculated for ( beta ) c 17 h 20 n 2 . hbr . 1 / 4h 2 o : c , 60 . 45 ; h , 6 . 42 ; n , 8 . 27 . found : c , 60 . 46 ; h , 6 . 44 ; n , 8 . 27 . following the procedure of example 17 but substituting thiophene for n - methylpyrrole , there was produced 2 ( 2 - thienyl ) phenethylamine as an oil . this oil ( 7 . 2 g , 0 . 03 mole ) was treated with 3 . 0 g of alpha - angelicalactone in 20 ml of methylene chloride . the solution was heated at reflux for ten minutes and the solvent was evaporated . the residue was dissolved in 50 ml of asolute ethanol , treated with 10 ml of ethereal hcl , and heated to remove most of the ether . the mixture was refluxed for four hours then evaporated to dryness . the material was purified by hplc on silica ( ethyl acetate / hexane , 2 : 1 ) to give an off - white solid lactam ( 3 . 6 g ). the lactam ( 3 . 5 g , 12 . 4 mmole ) in 40 ml of dry thf was added to 32 ml of 1m borane - thf at 22 ° c . the reaction was heated at reflux for two hours . after cooling , 10 ml of water was added slowly , followed by 12 ml of concentrated hcl . about 50 ml of thf was removed by distillation and the residue was allowed to cool . it was basified with 3n naoh and extracted with methylene chloride . the combined extracts were dried ( na 2 so 4 ) and concentrated to give a tan , oily amine product ( 3 . 5 g ). the perchlorate salt was prepared and recrystallized from methanol / ethyl acetate ( 1 : 1 ), affording off - white crystals , mp 216 °- 219 ° c . ( dec ). elemental analysis : calculated for c 17 h 19 ns . hclo 4 : c , 55 . 21 ; h , 5 . 45 ; cl , 9 . 58 . found : c , 55 . 36 ; h . 5 . 40 ; cl , 8 . 63 . 2 - amino - 1 - phenylethanol ( 100 g , 0 . 73 mole ) was combined with thiophene ( 150 ml ) and cooled in an ice bath as trifluoroacetic acid ( 175 ml ) was added . the reaction was refluxed for 2 hours and then evaporated in vacuo to an oil . the oil was dissolved in methylene chloride and washed once with 5 % naoh , once with water , once with brine , dried ( k 2 co 3 ) and evaporated in vacuo to an oil ( 135 . 8 g ). the oil was distilled on a kugelrohr apparatus ( 0 . 8 mm at 140 ° c .) to give a syrup ( 90 . 6 g ). this syrup was combined with t - butanol ( 250 ml ) and 30 % koh ( 810 ml ) and refluxed for 18 hours . after cooling , the reaction was extracted with ether and the ethereal solution was washed once with water , once with brine , dried ( na 2 so 4 ) and evaporated in vacuo to give a syrup ( 62 . 7 g ). the syrup was dissolved in ether and hcl gas was bubbled into the solution to give the hydrochloride salt which was recrystallized once from etoh / et 2 o to give a white solid . the salt was converted to its free base by extraction between 5 % naoh and ether and the ethereal solution was dried ( na 2 so 4 ) and evaporated in vacuo to give an oil ( 41 . 9 g ), which was 85 % of the 2 - thienyl isomer and 15 % of the 3 - thienyl isomer . this mixture ( 41 . 3 g ) was combined with succinic anhydride ( 20 . 3 g , 0 . 20 mole ) in 150 ml of thf . the solvent was evaporated to an oil which was heated at 150 ° c . for 40 hours , cooled and dissolved in 50 ml of i - proh which rapidly crystallized . after cooling , the white solid imide product was filtered ( 48 . 8 g ), mp 113 °- 114 ° c . the imide ( 43 . 2 g , 0 . 152 mole ) was partially dissolved in 600 ml of etoh , cooled to 0 ° c . and nabh 4 ( 23 . 0 g , 0 . 6 mole ) was added . the temperature was maintained at - 5 ° to 0 ° c . while ten drops of methane sulfonic acid was initially added and then over the next three hours 6 - 8 drops of 2n methanesulfonic acid in ethanol was added every 15 minutes . the temperature was maintained at 0 ° to 10 ° c . while the 2n acid was added more quickly over the next 1 . 5 hours with vigorous stirring to ph 1 . the reaction was stirred at room temperature for 16 hours and partitioned between ch 2 cl 2 and water . the organic layer was washed once with water , once with brine , dried ( mgso 4 ) and evaporated in vacuo to give an oil ( 43 . 6 g ). the oil was combined with 400 ml of ethanol and 10 ml of ethereal hcl and refluxed for two hours . the solution was evaporated in vacuo to give white solid lactam products . separation by preparative hplc on silica ( ethyl acetate / hexane 1 : 1 ) gave 4 , 5 , 7 , 8 , 9 , 9a - alpha - hexahydro - 4 - alpha - phenylthieno [ 2 , 3 - g ] indolizin - 7 - one ( 19 . 1 g ) and 4 , 5 , 7 , 8 , 9 , 9a - alpha - hexahydro - 4 - alpha - phenylthieno [ 3 , 2 - g ] indolizin - 7 - one ( 4 . 7 g ). 4 , 5 , 7 , 8 , 9 , 9a - alpha - hexahydro - 4 - alpha - phenylthieno [ 2 , 3 - g ]- indolizin - 7 - one ( 18 . 9 g ) was combined with 150 ml of dimethylsulfoxide , 15 ml of water and 50 g of k 2 co 3 and refluxed under n 2 for two hours . the reaction was cooled and partitioned between water and chloroform . the organic solution was washed three times with water , once with brine , dried ( k 2 co 3 ) and evaporated in vacuo to give a brown solid ( 16 . 9 g ). this mixture ( 2 : 3 ) of lactams ( 14 . 4 g , 0 . 054 mole ) was dissolved in 50 ml of dry thf and added to 125 ml of 1m bh 3 . thf in thf at 0 ° c . the solution was refluxed for 1 . 5 hours , cooled and water ( 25 ml ) cautiously added , followed by 12n hcl ( 37 . 5 ml ). the solution was heated to reflux , the thf was removed by distillation and the residual aqueous solution refluxed for another 15 minutes . the solution was cooled , diluted with water ( 200 ml ), adjusted to ph 11 with 10 % naoh and extracted with ch 2 cl 2 . the organic layer was washed once with water , once with brine , dried ( k 2 co 3 ) and evaporated in vacuo to give the oily amines ( 11 . 9 g , 87 %). the amines were separated using preparative hplc on silica ( etoac / meoh 19 : 1 ) to give 4 , 5 , 7 , 8 , 9 , 9a - alpha - hexahydro - 4 - alpha - phenylthieno [ 2 , 3 - g ] indolizine ( 5 . 7 g ) and 4 , 5 , 7 , 8 , 9 , 9a - beta - hexahydro - 4 - alpha - phenylthieno [ 2 , 3 - g ] indolizine ( 5 . 4 g ). the 4 , 5 , 7 , 8 , 9 , 9a - alpha - hexahydro - 4 - alpha - phenylthieno [ 2 , 3 - g ] indolizine amine was converted to its hbr salt and recrystallized from meoh / i - proh to give white crystals ( 6 . 0 g ) mp 198 °- 200 ° c . the 4 , 5 , 7 , 8 , 9 , 9a - beta - hexahydro - 4 - alpha - phenylthieno [ 2 , 3 - g ] indolizine amine was also converted to its hbr salt and recrystallized from meoh to give white crystals ( 3 . 28 g ), mp 236 °- 239 ° c . elemental analysis : calculated for c 16 h 17 ns . hbr : c , 57 . 15 ; h , 5 . 39 ; n , 4 . 17 . found ( i - alpha ): c , 57 . 16 ; h , 5 , 44 ; n , 4 . 25 . found ( i - beta ) : c , 57 . 11 ; h , 5 . 44 ; n , 4 . 13 . 4 , 5 , 7 , 8 , 9 , 9a - alpha - hexahydro - 4 - alpha - phenylthieno [ 3 , 2 - g ] indolizin - 7 - one ( 4 . 0 g ) was reduced with 1m bh 3 . thf ( 40 . 0 ml ) in a similar manner as above to give 4 , 5 , 7 , 8 , 9 , 9a - alpha - hexahydro - 4 - alpha - phenylthieno [ 3 , 2 - g ] indolizine ( 3 . 8 g ). this was converted to its hbr salt , which was recrystallized from meoh / i - proh to give white crystals ( 2 . 62 g ), mp 203 . 5 °- 205 ° c . elemental analysis : calculated for c 16 h 17 ns . hbr : c , 57 . 15 ; h , 5 . 39 ; n , 4 . 17 . found ( ii - alpha ): c , 57 . 08 ; h , 5 . 42 ; n , 4 . 20 . thiophene ( 60 . 0 g , 0 . 71 mole ) and 2 - aminoacetalde diethyl acetal ( 35 . 4 g , 0 . 26 mole ) were combined in 50 ml of glacial acetic acid . the mixture was cooled to 0 ° c . and 50 ml of conc . h 2 so 4 was added dropwise . the solution was allowed warm to room temperature . the mixture was added to ice water and extracted once with ether . the aqueous solution was basified with 50 % naoh and extracted with methylene chloride . the organic layers were washed once with brine , dried ( k 2 co 3 ) and evaporated in vacuo to an oil . the oil was distilled on a kugelrohr apparatus ( 1 mm , 150 ° c .) to give a yellow oily amine ( 20 . 4 g ). this amine in 90 ml of thf was added slowly to succinic anhydride ( 9 . 8 g , 0 . 098 mole ) in 150 ml of thf and the solution was evaporated to an oil which was heated at 140 ° c . for 12 hours . the oil was dissolved in ethyl acetate , treated with acetyl chloride ( 20 ml ), refluxed for one hour then evaporated in vacuo to an oily amide ( 23 . 5 g ). this imide in 300 ml of ethanol at 0 ° c . was combined with nabh ( 10 . 8 g , 0 . 28 mole ) and five drops of methanesulfonic acid were added . the temperature was lowered to - 5 ° c . while every 15 minutes five drops of 2n methanesulfonic acid in ethanol were added over the next four hours . the acid was added more rapidly with vigorous stirring to ph 3 and the mixture stirred at room temperature for 16 hours . the reaction was partitioned between water and methylene chloride and the organic layer was washed once with water , once with brine , dried ( mgso 4 ) and evaporated in vacuo to an oil ( 23 . 6 g ). the oil was combined with 250 ml of ethanol and 5 ml of ethereal hcl , refluxed for five hours and evaporated to give a mixture of lactams ( 18 . 8 g ). the lactams were combined with 150 ml of dmso , 15 ml of water , 50 g of k 2 co 3 and refluxed under n 2 for 40 minutes . the solution was cooled and partitioned between water and chloroform . the organic layer was washed twice with water , once with brine , dried ( mgso 4 ) and evaporated in vacuo to give an oil ( 18 . 4 g ). these lactams were separated by preparative hplc on silica using ethyl acetate / hexane 1 : 1 to give the 9a - alpha - 4 - alpha lactam ( 8 . 1 g ) and the 9a - beta - 4 - alpha lactam ( 6 . 2 g ). the 9a - beta - 4 - alpha lactam ( 5 . 6 g ) in 30 ml of thf was added to 50 ml of 1m bh 3 thf and refluxed for 1 . 5 hours . the cooled solution had 10 ml of water and 15 ml of 12n hcl slowly added and the thf was removed by distillation . the residual aqueous solution was refluxed for ten minutes , cooled , basified with 3n naoh and extracted with methylene chloride . the organic solution was washed once with water , once with brine , dried ( k 2 co 3 ) and evaporated in vacuo to give an oily amine ( 5 . 4 g ). the amine was converted to its hbr salt in i - proh and recrystallized ( meoh / i - proh / et 2 o ) to give white crystals ( 3 . 1 g ), mp 238 °- 239 ° c . of 4 , 5 , 7 , 8 , 9 , 9a - beta - hexahydro - 4 - alpha -( 2 - thienyl ) thieno [ 2 , 3 - g ] indolizine hydrobromide . the 9a - alpha - 4 - alpha lactam ( 5 . 8 g ) in 25 ml of thf was added to 50 ml of 1m bh 3 . thf and refluxed for 1 . 5 hours . ten ml of water and 15 ml of 12n hcl were added cautiously to the cooled solution and the thf was removed by distillation . the residual aqueous solution was refluxed for ten minutes , cooled and made alkaline with 1n naoh . the solution was extracted with methylene chloride and the organic solution was washed once with water , once with brine , dried ( k 2 co 3 ) and evaporated in vacuo to give a mixture of amines ( 5 . 6 g ). this mixture was converted to its hbr salt in i - proh and recrystallized twice from etoh and once from meoh / i - proh to give white crystals ( 2 . 5 g ), mp 187 °- 189 . 5 ° c . of 4 , 5 , 7 , 8 , 9 , 9a - alpha - hexahydro - 4 - alpha -( 2 - thienyl ) thieno [ 2 , 3 - g ] indolizine hydrobromide . elemental analysis : calculated for c 14 h 15 ns 2 . hbr : c , 49 . 12 ; h , 4 . 71 ; n , 4 . 09 . found ( alpha ): c , 49 . 47 ; h , 4 . 31 ; n , 4 . 25 . found ( beta ): c , 49 . 16 ; h , 4 . 71 ; n , 4 . 06 . a mixture of 110 . 9 g ( 1 . 098 mole ) of succinic anhydride and 985 ml of thf was cooled to 10 ° c . and a solution of 140 . 53 g ( 1 . 098 mole ) of 2 -( 2 - aminoethyl )- 1 - methylpyrrole in 1400 ml of thf was added dropwise over a period of thirty minutes while stirring under an atmosphere of argon , the temperature being maintained at 10 to 15 ° c . after the addition was complete , stirring was continued an additional one hour and then the solvent removed in vacuo to give a dark - brown , oily residue . the residue was stirred and heated at 175 ° in an oil bath for three hours under an atmosphere of argon . the residue was distilled on a kugelrohr apparatus , collecting the product imide at 170 ° c ./ 0 . 06 mm , which crystallized to yield an off white solid , mp 116 °- 121 ° c . a small sample of the intermediate imide was recrystallized from ethanol to yield a white solid , mp 120 °- 122 ° c . a solution of 100 g ( 0 . 485 mole ) of the above - obtained crude imide was added to 3 - 1 of 90 % aqueous ethanol and the mixture cooled in an ice bath to about 3 ° c . sodium borohydride ( 68 . 42 g ; 1 . 81 moles ) was added and about 25 ml of 2n hydrochloric acid was added dropwise with stirring over a five hour period by means of a metering pump while maintaining a temperature of 0 ° to 3 ° c . after the addition was complete ( ph = 8 - 9 ), the reaction was acidified with 1 - 1 of 2n hydrochloric acid over a period of 1 . 5 hours while maintaining a temperature of less than 10 ° c . stirring ( under nitrogen ) was continued overnight as the temperature was allowed to gradually warm to ambient , during which time the mixture became a clear , colorless solution . the solvent was partially removed in vacuo using low heat to a final volume of about 800 mls , diluted with 800 mls of water and extracted three times with 300 ml portions of methylene chloride . the combined extracts were washed with 300 ml of water , 300 ml of brine , and dried over anhydrous potassium carbonate . the solvent was removed in vacuo to give 31 . 07 g of a crude tan solid . the crude solid was recrystallized from about 100 ml of hot etoac to give 23 . 76 g of nearly pure 4 , 5 , 7 , 8 , 9 , 9a - hexahydro - 3 - methyl - 3h - pyrrolo [ 2 , 3 - g ] indolizin - 7 - one , an off - white solid , mp 122 °- 125 ° c . a solution of 18 . 0 g ( 0 . 0946 mole ) of 4 , 5 , 7 , 8 , 9 , 9a - hexahydro - 3 - methyl - 3h - pyrrolo [ 2 , 3 - g ] indolizin - 7 - one ( the product of example 21 ) in 250 ml of dry thf was stirred under an atmosphere of argon in flame - dried glassware at a temperature of 5 ° to 10 ° c . while adding 52 ml of 1 . 82m phenyllithium in ether solution over a period of ten minutes . after the addition was complete , the cooling bath was removed and stirring continued for thirty minutes . the reaction mixture was carefully poured onto 100 g of ice and diluted with about 1 - 1 of brine . the organics were extracted into three 250 ml portions of ether and the combined extracts washed twice with brine and dried over anhydrous potassium carbonate . the solvent was removed in vacuo to give 23 . 7 g of a light - brown oily residue . a slurry of 3 . 59 g ( 0 . 0946 mole ) of lah in 150 ml of anhydrous ether was treated cautiously dropwise with a freshly prepared solution of 12 . 61 g ( 0 . 0946 mole ) of anhydrous aluminum chloride in 150 ml of dry ether under an atmosphere of nitrogen in flame - dried glassware . an additional 100 ml of anhydrous ether was added and 23 . 7 g of the above - isolated oil was carefully added portionwise over a period of about ten minutes . stirring was continued overnight at room temperature . water was added cautiously dropwise and the resulting mixture cooled in an ice bath and treated with 3n sodium hydroxide solution to ph & gt ; 9 . an additional 600 ml of water was added and the organics extracted three times with methylene chloride . the combined extracts were washed twice with brine , dried over anhydrous potassium carbonate , and concentrated in vaco to give 19 . 35 g of a light brown , oily residue , containing an isomeric mixture of 4 , 5 , 7 , 8 , 9 , 9a - alpha - hexahydro - 3 - methyl - 7 - phenyl - 3h - pyrrolo [ 2 , 3 - g ] indolizine and 4 , 5 , 7 , 8 , 9 , 9a - beta - hexahydro - 3 - methyl - 7 - phenyl - 3h - pyrrolo [ 2 , 3 - g ] indolizine . the mixture was separated into its alpha and beta isomers by hplc , eluting with a solvent mixture of 95 : 5 :: toluene : ethyl acetate . the early fractions were combined to give 5 . 17 g of crude front running isomer and the latter fractions combined to give 3 . 58 of the slower moving isomer , both as oils . the crude front running isomer obtained in the first fractions was converted to a crude hydrochloride salt by treatment of an isopropanol solution of the oil with a slight excess of anhydrous hydrogen chloride . the crude hydrochloride salt was recrystallized once from meoh / i - proh / et 2 o and once from etoh / et 2 o to yield pure first isomer of 4 , 5 , 7 , 8 , 9 , 9a - hexahydro - 3 - methyl - 7 - phenyl - 3h - pyrrolo [ 2 , 3 - g ] indolizine hydrochloride hydrate ethanolate , a white solid , mp 170 °- 173 ° c . in a manner similar to the above , the crude oily slower running isomer obtained from the latter hplc fractions was converted to its hydrochloride salt . pure second isomer of 4 , 5 , 7 , 8 , 9 , 9a - hexahydro - 3 - methyl - 7 - phenyl - 3h - pyrrolo [ 2 , 3 - g ] indolizine hydrochloride hydrate 2 - propanolate ( 42 : 42 : 7 : 3 ) was obtained as a tan solid , mp 181 °- 183 ° c ., by recrystallization of the crude salt from meoh / 2 - proh / et 2 o . elemental analysis ( front running isomer ): calculated for c7h 20 n 2 . hcl . 1 / 6c 2 h 6 o . 1 / 3h 2 o : c , 68 . 82 ; h , 7 . 55 ; n , 9 . 26 ; h 2 o , 1 . 99 . found : c , 68 . 76 ; h , 7 . 53 ; n , 9 . 23 ; h 2 o , 1 . 86 . elemental analysis ( slower running isomer ): calculated for c7h 20 n 2 . hcl ; 1 / 6h 2 o . 1 / 14c 3 h 8 o : c , 69 . 82 ; h , 7 . 46 ; n , 9 . 46 ; ho , 1 . 01 . found : c , 69 . 85 ; h , 7 . 52 ; n , 9 . 43 ; ho , 0 . 98 .