Patent GB-1201061-A (GB)
Title: Oxo pyrroles and process for preparing same
IPC: C07D207/337
Filed: 1967-08-08
Abstract: 1,201,061. Oxo-pyrrole derivatives. ENDO LABORATORIES Inc. 8 Aug., 1967 [26 Aug., 1966; 6 Dec., 1966], No. 36464/67. Heading C2C. Compounds of Formula A wherein R 1  designates hydrogen, a lower alkyl group having a maximum of 6 carbon atoms, phenyl, phenyl alkyl (where the alkyl group has up to 3 carbons), substituted phenyl or substituted phenyl alkyl in which the substituent on the phenyl ring is halogen, alkyl of not more than four carbon atoms, alkoxy of not more than four carbon atoms or halogenated alkyl of not more than four carbon atoms, or 2-, 3- or 4-pyridyl; R 2 , R 3  and R 4  designate alkyl, alkenyl or cycloalkyl having a maximum of 8 carbon atoms, phenyl, halophenyl, (lower alkoxy) phenyl, thienyl, furyl, or benzyl; R 3  and R 4  may be linked to constitute an alicyclic ring having a maximum of 8 carbon atoms; R 5  designates hydrogen, alkyl, alkenyl or cycloalkyl having a maximum of 8 carbon atoms, phenyl or benzyl; R 2  and R 5  may be linked to constitute an alicyclic ring having a maximum of 8 carbon atoms; wherein when a 5-aminomethyl - 4,5,6,7 - tetrahydro - 4 - oxoindole is formed it may be substituted by a lower alkyl group attached to carbon atom 6 or 7 of the indole nucleus, R 3  and R 5  may be linked to constitute an alicyclic ring having a maximum of 8 carbon atoms, which ring may be substituted by an alkyl or alkylidene group having up to four carbons, a benzylidene or a benzyl group; and X and Y are each the same or different and are hydrogen, lower alkyl, lower alkynyl, lower alkenyl, cycloalkyl, hydroxylower alkyl, alkoxy-lower alkyl, dialkylamino, lower acyloxy-alkyl, carbamyloxy-lower alkyl, phenyl-lower alkyl, heterocyclo and heterocyclo lower alkyl; and wherein X and Y may be linked, and when linked constitute a heterocyclic ring of not more than eight members, are prepared by reaction of one mole of a base of formula HNXY with a compound of Formula B or by the action of 2 moles of said base a compound of Formula C wherein R 6 , R 7  and R 8  are C 1-4  carbon atoms or R 6  and R 7  may be linked to constitute a ring of not more than seven carbon atoms and Z is an inorganic ion. The compound of Formula B may be formed in situ by the alkaline treatment of compounds of Formula C. The term lower, unless otherwise indicated, denotes groups containing up to 5 carbon atoms. Certain compounds of Formula A are novel, including compounds of formula wherein R 1 , R 2  and R 4  are hydrogen, alkyl having a maximum of six carbon atoms, phenyl, phenyl alkyl whereof the connecting alkyl or linking alkyl group has a maximum of three carbon atoms, substituted phenyl and substituted phenyl alkyl aforesaid, in which the substituent on the phenyl ring is halogen, alkyl of not more than four carbon atoms, alkoxy of not more than four carbon atoms or halogenated alkyl or not more than four carbon atoms; n is selected from the integers 0, 1, 2 and 3; X and Y are each the same or different and are hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, hydroxy-lower alkyl, alkoxy-lower alkyl, dialkylamino, lower acyloxyalkyl, carbamyloxy-lower alkyl, phenyl-lower alkyl, heterocyclo and heterocyclo lower alkyl; and wherein X and Y may be linked, and when linked constitute a heterocyclic ring of not more than eight members and the pharmaceutically acceptable salts of these where lower has the above meaning. The compounds of Formula A are stated to have central nervous system activity and are useful as tranquilizers and antidepressants. The quatenary salts of Formula C above are prepared by quaternization of the corresponding tertiary amines which may be prepared by reaction of the amine HNR 6 R 7  and formaldehyde with the appropriate ketone of formula 4 - Butyl - 3,5 - dimethylpyrrol - 3 - yl methyl ketone is prepared by the Knorr synthesis from 2,4-pentane-dione and 2-oximino-3-heptanone. 1,3 - Dimethyl- and 1,2,3 - trimethyl - 4,5,6,7- tetrahydro - 4 - oxoisoindole are prepared by cyclization of 4 - (2,5 - dimethyl - 3 - pyrryl)- butyric acid and 4-(1,2,5-trimethyl-3-pyrryl)- butyric acid respectively which themselves are prepared by reduction of the corresponding 4-oxobutyric acids prepared by action of succinic anhydride and BF 3  on the di- or tri-methylpyrrole.