Patent GB-1257199-A (GB)
IPC: C07D317/68
Filed: 1969-08-14
Abstract: 1,257,199. N,N<SP>1</SP>-Alkylene bis-(benzamides). STERLING DRUG Inc. 14 Aug., 1969 [30 Aug., 1968], No. 40793/69. Heading C2C. Novel N,N<SP>1</SP>-alkylene bis-(benzamides) of the formulµ and where Q is C 1-6  alkyl, C 3-6  alkoxyalkyl, C 3-6  alkenyl, halo-C 1-6  alkyl, halo-C 2-6  alkenyl, C 3-6  cycloalkyl phenyl or BN-(C 1-6  alkyl), where BN is di-(C 1-6  alkyl) amino or a 5-7 membered saturated nitrogen containing monocyclic heterocyclic ring, R is H or C 1-6  alkyl, Y is C 5-12  alkylene, having at least 5 carbon atoms between its 2 connecting linkages, wherein a carbon atom of said alkylene more than 2 carbon atoms removed from the amide N atoms can be replaced by -O-, -S-, -S-S-, -Se- Se-, =SO, =SO 2 , =NH, =N-(C 1-6  alkyl), =N-(CO-phenyl-4-10-Q),=C=O, -CH = CH- or -C#C-, or Y is Y<SP>1</SP>-Z-Y<SP>11</SP>, where Y<SP>1</SP> is C 1-4  alkylene, Y<SP>11</SP> is a direct linkage ; or C 1-4  alkylene, Z is phenyl or C 3-6  cycloalkyl,  and 'the benzene ring of the phenyl radical of Formula I is, if desired, further substituted by, for example, C 1-6  alkyl, C 1-6  alkoxy, halogen, benzyloxy or OH are prepared by reacting an amine of the formula RNH-Y-NHR with at least two molar equivalents of the appropriate benzoylating agents. In addition, compounds, formula I, in which the phenyl radical is substituted by OH may be obtained by hydrogenolysis of the corresponding benzyloxy substituted compounds, compounds in which Q is di-(C 1-6  alkyl) amino (C 1-6  alkyl) by reacting the corresponding compounds in which Q is OH with the appropriate di-.(C 1-6  alkyl) amino-(C 1-6  alkyl) halides, and compounds, in which the alkylene chain Y is interrupted by = C = 0, by hydrolysing the corresponding ethylene ketals. In comparative examples, N,N<SP>1</SP> - heptamethylene bis - (3 - methoxybenzamide, N,N<SP>1</SP>- heptamethylene bis (2 - methoxybenzamide), N,N<SP>1</SP> - heptamethylene bis - (4 - methylthiobenzamide) and N,N<SP>1</SP>-hexamethylene bis-(4-hydroxybenzamide) are made by reacting the appropriate amines with the corresponding acid chlorides or esters. N,N<SP>1</SP> - Heptamethylene bis - (4 - hydroxybenzamide) is obtained by hydrolysing N,N<SP>1</SP> - heptamethylene bis-(4-acetoxybenzamide) which is made by reacting 1,7-heptanediamine with 4-acetoxybenzoyl chloride. The following intermediates are also prepared: 4-trideuteromethoxy benzoic acid, acid chloride and ethyl ester thereof, 4-ethoxybenzoyl chloride, 4-acetoxybenzoic acid and acid chloride, 4 - (2,2,2 - trifluoroethoxy) benzoic acid, acid chloride and ethyl ester, 4-(2,2-dichlorovinyloxy) benzoic acid, acid chloride and ester, 4-allyloxybenzoic acid, acid chloride and ester, 3,5- dibenzyloxy - 4 - methoxy -benzoic acid, acid chloride and methyl ester, 4-pentadeuteroethoxybenzoic acid, acid chloride and ethyl ester, 2,8-nonanediamine, ethylene ketal of 1,4 - diamino - 4-heptanone, ethylene ketal of N,N<SP>1</SP> - (4 - oxoheptamethylene) bis - (phthalimide), 1,1,5 - trimethyl -1,7 - heptanediamine, N 1  - acetyl - 1,1,5 - trimethyl - 1,7 - heptanediamine, N,N<SP>1</SP> - dimethyl 1,7 - heptanediamine, N,N<SP>1</SP> - dibenzal - 1,7 - heptanediamine, and the dimethiodide thereof, 3-heptyne-1,7- diamine, 7 - chloro - 3 - heptyne - 1 - ol, 7-chloro- 3-heptyne-1-yl-4-toluene sulphonate, N,N<SP>1</SP>- (3 - heptyne-1,7 - diyl) bis - phthalimide, 1,4,7- heptane - triamine, N,N<SP>1</SP>N<SP>11</SP> - (1,4,7 - heptamethylene) tris - phthalamide, and 4 - (2- methoxyethoxy) benzoic acid Pharmaceutical compositions, suitable for oral or parenteral administration and having adrenal hypertrophy, antifertility and hypocholestremic activities, contain the above novel compounds and conventional pharmaceutically acceptable carriers.