4 - benzazonin derivatives, their salts, processes for their manufacture and product

摘要

1443311 Benzazonine derivatives NIHON IYAKUHIN KOGYO CO Ltd 3 May 1974 [8 May 1973 (4) 16 Jan 1974 5 Feb 1974 (2)] 19567/74 Heading C2C Novel compounds I (R is H, OH, or 1-3C alkoxy; R 1 is H or 1-3C alkyl; R 2 is H, Me or Et; R 3 is H, linear or branched, saturated or unsaturated 1-4C aliphatic hydrocarbyl, mono- or di-hydroxy- 1-2C alkyl, 3-6C cycloalkyl, 6-8C optionally substituted aromatic hydrocarbyl or phenethyl; and R 4 is H, OH or oxo) and pharmaceutically acceptable salts thereof are prepared by (1) reduction of a compound I in which R 4 is oxo to give one in which R 4 is OH; (2) reacting a compound II (RSP11/SP is H or methoxy, Z is an inorganic acid) with formaldehyde to give a compound I in which R 4 is oxo, followed if desired by reduction to one in which R 4 is OH; (3) reacting a compound I in which R 3 is H and R 4 is OH with red phosphorus and HI to give a compound I in which R 3 is H (4) reacting a compound I in which R is OH and R 4 is H with a methoxylating agent; (5) reaction of a compound III with a compound XCH 2 A 2 (X is halo, alkylsulphonyloxy or arylsulphonyloxy and A 2 is alkyl, vinyl, 2,2-dimethylvinyl phenyl or benzyl to give a compound I in which R 3 is A 2 and R 4 is H; (6) reaction of a compound III with a compound A 2 CHO in the presence of HCOOH or H 2 activated by a catalyst to give a compound I in which R 3 is A 2 and R 4 is H; (7) reaction of a compound III with a compound A 2 COY (Y= halo) followed by reduction with a complex metal hydride to give a compound I in which R 3 is A 2 and R 4 is H; (8) reduction of a compound I in which R 4 is oxo and R is H or methoxy to give a compound I in which R 4 is H; (9) reaction of a compound IV with a compound X-CH 2 A 3 (A 3 is alkyl, alkenyl, cycloalkyl, phenyl, phenylmethyl, hydroxymethyl or 1,2-dihydroxyethyl) to give a compound I in which R 3 is A 3 and R 4 is OH; (10) reaction of a compound IV with a compound A 4 COY (A 4 is alkyl, alkenyl, cycloalkyl, phenyl or phenylmethyl) followed by reduction with a complex metal hydride to give a compound I in which R 3 is A 4 and R 4 is OH; (11) reduction of a compound V (B is CO or CH 2 ) to give a compound I in which R 3 is A 3 and R 4 is OH; (12) reduction of a compound VI (A 5 is alkyl, cycloalkyl, aryl or hydroxyalkyl) to give a compound I in which R 3 is A 5 and R 4 is H or OH depending on the reducing agent used; or (13) hydrolysis of a compound I in which R is methoxy to give one in which R is OH. Pharmaceutical compositions having CNS activity comprise a compound I together with a suitable carrier or diluent.