Patent GB-1205995-A (GB)
Title: Novel benzodiazepine derivatives and a process for the manufacture thereof
IPC: A61K31/00
Filed: 1968-07-02
Abstract: 1,205,995. Benzodiazepine derivatives. F. HOFFMANN-LA ROCHE & CO. A.G. 2 July, 1968 [3 July, 1967 (2)], No. 31473/68. Heading C2C. Compounds of the general formulµ (A represents B represents CO or CH 2 , X<SP>1</SP> and X<SP>2</SP> represent halogen, R represents halogen, NO 2  or CF 3 , R<SP>1</SP> represents C 1-7  alkyl, C 2-7  alkanoyloxy or a group of the formula R<SP>2</SP> represents OH, C 1-7  alkoxy or C 2-7  alkanoyloxy, R<SP>3</SP> represents C 1-7  alkyl, R<SP>4</SP> represents 2,6-dihalophenyl or, in the case of Formula Ia, 2,3-dihalophenyl when R<SP>1</SP> (when present) represents C 1-7  alkyl and R<SP>2</SP> is absent, R<SP>5</SP> and R<SP>6</SP> represent C 1-7  alkyl or NR<SP>5</SP>R<SP>6</SP> represents 5- or 6-membered heterocyclic ring, R<SP>10</SP> and R<SP>30</SP> represent C 1-7  alkyl, n = 2-5 and the broken lines denote optional substituents-provided that when R<SP>2</SP> is present A represents a group of formula (i) or (ii)) and their acid addition salts are prepared by (a) cyclizing a compound of the formula where a compound of Formula (Ia) in which A represents grouping (i) and R<SP>2</SP> is absent is required, (b) treating a compound of the formula with a compound of the formula or an ester thereof, in the presence of an ion of a strong acid, where a compound of Formula (Ia) in which A represents grouping (i), B represents CO and R<SP>2</SP> is absent is required, (c) nitrating a compound of Formula (Id) or (Ib) in which A represents grouping (i) or (iii) and R is absent, (d) introducing a C 1-7  alkyl or C 2-7  alkanoyl group or a group of Formula (iv) into the 1-position of a compound of Formula (Ia), (e) reducing a compound of Formula (Ia) or (Ib) in which a 4,5-double bond is present, (f) treating a compound of Formula (Ia) in which B = CO with LiAlH 4 , (g) oxidizing a compound of Formula (Ia) in which A represents grouping (i), (h) treating a compound of Formula (Ia) in which R<SP>1</SP> is absent and B = CO with a compound of the formula in the presence of TiCl 4  or p-toluenesulphonic acid, (i) deoxygenating a compound of Formula (Ia) or (Ib) in which A represents grouping (iii), (j) treating a compound of Formula (Ia) or (Ib) in which A represents grouping (iii) and R 2  is absent with a C 2-7  alkanoic acid anhydride, (k) hydrolysing a compound of Formula (Ia) or (Ib) which carries a 3-alkanoyloxy group, (1) treating a compound corresponding to Formula (Ia) but which carries a group of the formula -C n H 2n  halogen in the 1-position with a compound of the formula D shown above, (m) alkylating a compound corresponding to Formula (Ic) but which is unsubstituted at the 4-position and which may also be unsubstituted at the 1-position, (n) cyclizing a compound of the general formula (lower = C 1-7 ) by treatment with a dehydrating agent, or (o) oxidizing a compound of Formula (Ia) in which B represents CH 2 , A represents grouping (i), R<SP>1</SP> represents a C 1-7  alkyl group and R<SP>2</SP> and R<SP>3</SP> are absent, optionally followed in each case by salt formation. The above compounds are sedatives, psychosedatives, hypnotics, muscle relaxants and anticonvulsants, and may be administered in the form of pharmaceutical preparations containing them in association with a carrier.