Patent GB-585363-A (GB)
Title: New heterocyclic compounds
IPC: C07D221/10
Filed: 1944-08-31
Abstract: Quinoline and quinazoline derivatives, carrying in 2- or 4-position an arylamino group free from acidic substituents and in the 4- or 2-position a basic group of the general formula -NR11-A-NRR1, wherein R11 represents H, alkyl or substituted alkyl, A represents an aliphatic, alicyclic or aliphatic-carbocyclic linking group, free from acidic substituents, and -NRR1 is a strongly basic amino or substituted amino group, are obtained by interaction of a diamine of the general formula NHR11-A-NRR1 with an appropriate 2- or 4-arylamino-quinoline or quinazoline, free from acidic substituents and carrying in the 4- or 2-position a labile atom or group, e.g. halogen or an alkoxy, aryloxy or alkylmercapto group.  Alternatively, the 4- or 2-substituent may be introduced in stages by interaction of the appropriate arylamino-quinoline or quinazoline with a compound of the general formula NHR11-A1-B, wherein A1 represents the whole or part of the linking group and B represents a reactive group and reacting the product with ammonia or a primary or secondary amine to form the group -NRR1 or a group -A11-NRR1 such that A1 and A11 together constitute the group A. Another alternative when both R and R1 represent hydrogen is to react the labile group in the 2-or 4-position of the arylamino-quinoline or quinazoline compound with an acylated diamine NH.R11-A-NH.Ac, the acyl group being subsequently hydrolysed off.  The free amino group so generated may be modified as by alkylation, conversion to a heterocyclic group such as piperidino or by reaction with a halogeno-substituted amine Hal-A11-NRR1 so as to extend the linking group A to A-NH-A111.  Examples relate to the interaction of (1) 4-chloro-2-p-chloroanilinoquinazoline with b  - diethylaminoethylamino, (2) 4 - chloro - 2 - p - chloroanilinoquinazoline with g  - diethylaminopropylamine, (3) to (8), 4-chloro-2-p-methoxyanilino-quinazoline with g  - diethylaminopropylamine, (4) b  - dimethylaminoethylamine, (5) g  - dimethylaminopropylamine, (6) g  - piperidinopropylamine, (7) g  - butylaminopropylamine, (8) d  - diethylaminobutyamine, (9) 4 - chloro - 2 - p - chloronilinoquinazoline with b -acetylaminoethylamine, with subsequent hydrolysis of the acetyl group, (10) 2 - p - chloroanil - 4 - ethoxyquinazoline with b -diethylaminoethylamine, (11) to (17), 2 - p - chloroanilino-4-ethoxyquinazoline with (11) g  - dibutylaminopropylamine, (12) d  - dibutylaminobutylamine, (13) d  - dimethylaminobutylamine, (14) 5 - dimethylamino amylamine, (15) 6 - dimethylaminohexylamine, (16) b  - piperidinopropylamine, (17) g  - (N - methyl - N - isopropylamino) - propylamine; (18) 2 - chloro - 4 - p - chloroanilinoquinazoline with g -diethylaminopropylamine; (19) to (26) 2 - p - chloroanilino - 4 - ethoxyquinazoline with (19) 5-diethylamino-2-aminopentane, (20) b  - piperidinoethylamine, (21) b - pyrrolidinoethylamine, (22) b  - piperidino - a  - methylethylamine, (23) ö - butylaminopropylamine, (24) ethylene diamine-hydrate, (25) hexamethylene diamine, (26) g -(N-methyl-N-b -diethylaminoethylamino) - propylamine; (27) 2 - p - chloroanilino-4-phenoxyquinazoline with b -diethylaminoethylamine, (28) 2-p-chloroanilino-4-methylthioquinazoline with b -diethylaminoethylamine, (29) 2 - p - chloroanilino - 4 - ethoxyquinazoline with N : N1-dimethyltrimethylene diamine; (30) and (31) 2-chloro-4 p-chloroanilinoquinoline with (30) b -diethylaminoethylamine, (31) g -di-n-butylaminopropylamine; (32) to (37) 2-p-chloroanilino-4 chloroquinoline with (32) b -diethylaminoethylamine, (33) g -diethylaminopropylamine, (34) g -piperidinopropylamine, (35) g -dimethylaminopropylamine, (36) d  - diethylaminobutylamine, (37) d  - diethylamino - a  - methyl - butylamine; (38) to (40) b -diethylaminoethylamine with (38) 2 - p - methoxyanilino - 4 - chloroquinoline, (39) 2 - p - methylanilino - 4 - chloroquinoline, (40) 2 - b  - naphthylamino - 4 - chloroquinoline; (41) to (44) g -diethylaminopropylamine with (41) 2 - p - chloroanilino - 4 - chloro - 7 : 8 - benzquinoline, (42) 2-(61-bromo-21-naphthylamino)-4-chloroquinoline, (43) 2-p-nitroanilino-4-chloroquinoline, (44) 2-p-chloroaniline-3-methyl-4-chloroquinoline.  Specification 585,362 is referred to.  Specification 579,502 also is referred to in the second Provisional Specification.  4 - Chloro - 2 - p - chloroanilinoquinazoline is obtained by treating with phosphorus oxychloride the product of reaction of 2-chloro-4-hydroxy-quinazoline with p-chloroaniline.  2 - p - Chloroanilino - 4 - ethoxyquinazoline, 2 - chloro - 4 - p - chloroanilino-quinazoline, 2 - p - chloroanilino - 4 - phenoxy - quinazoline and 2 - p - chloroanilino - 4 - methylthioquinazoline are obtained by the reaction of p-chloroaniline with 2-chloro-4-ethoxyquinazoline, 2 : 4-dichloroquinazoline, 2-chloro-4-phenoxyquinazoline and 2 - chloro - 4 - methylthioquinazoline respectively.