Patent GB-810846-A (GB)
Title: New pyrimidine compounds and processes for producing the same
Filed: 1956-07-04
Abstract: The invention comprises compounds of the general formula: <FORM:0810846/IV (b)/1> (wherein R is dimethylamino, diethylamino, methyl-ethyl-amino or a saturated nitrogen containing heterocyclic ring attached to the pyrimidine nucleus through the nitrogen atom, R1 is hydrogen or an alkyl radical, R2 is hydrogen, a halogen or an alkyl radical and "Aralkyl" is an aralkyl group which may be substituted in the aryl radical by a halogen atom), their acid-addition salts and their preparation by one of the following methods: (1) reaction of the appropriate 2-halogenopyrimidine with the appropriate aralkyl-mercaptan; (2) condensation of the appropriate isothiourea-aralkyl ether with a b -keto-carboxylic acid ester, halogenation of the resulting 4-hydroxy-pyrimidine and reaction of the 4-halogeno - pyrimidine with the appropriate secondary amine; and (3) reacting the appropriate 2 - mercapto - 4 - tertiary - aminopyrimidine with the appropriate aralkyl halide.  In examples: (1) 2-chloro-4-dimethylamino-6-methyl-pyrimidine and benzyl mercaptan are heated together to give 2-benzylmercapto-4-dimethylamino - 6 - methyl - pyrimidine hydrochloride from which the free base is subsequently isolated; (2) and (3) 2-o-chlorobenzylmercapto - 4 - piperidimo - 6 - methyl - pyrimidine hydrochloride, 2 - o - chlorobenzylmercapto - 4 - dimethylamino - pyrimidine hydrochloride and the free base, 2-o-chlorobenzylmercapto - 4 - dimethylamino - 5 - methyl - pyrimidine hydrochloride and the free base, 2-o-chlorobenzylmercapto-4-dimethylamino - 6 - ethyl - pyrimidine hydrochloride and the free base, 2-o-chlorobenzylmercapto-4-dimethylamino - 5 : 6 - dimethyl - pyrimidine hydrochloride and the free base, 2-p-chlorobenzylmercapto - 4 - dimethylamino - 6 - methyl - pyrimidine hydrochloride and the corresponding m-chloro-compound, and 2-o-chlorobenzylmercapto - 4 - dimethylamino - 5 - chloro - 6 - methyl - pyrimidine are prepared similarly; (4) b -phenylethyl-mercaptan and 2-chloro - 4 - dimethylamino - 6 - methyl - pyrimidine are either heated together at 200 DEG  C. or reacted together in pyridine in the presence of aqueous sodium hydroxide at below 30 DEG  C. with subsequent heating at 60 DEG  to 70 DEG  C. to give, on working up in each case, 2-b -phenylethyl - mercapto - 4 - dimethylamino - 6 - methyl-pyrimidine; (5) o-chlorobenzyl-isothiourea ether hydrochloride (prepared from o-chlorobenzylchloride and thiourea) and acetoacetic ester are reacted in the presence of sodium in alcohol to give 2 - o - chlorobenzylmercapto - 4 - hydroxy - 6 - methyl - pyrimidine, this with POCl3 gives 2 - o - chlorobenzylmercapto - 4 - chloro - 6 - methyl - pyrimidine and this on heating with dimethylamine in alcohol gives 2 - o - chlorobenzylmercapto - 4 - dimethylamino - 6 - methyl - pyrimidine hydrochloride from which the free base is subsequently isolated; and (6) 2-mercapto-4-dimethylamino-6-methyl-pyrimidine (prepared by boiling the 2-chloro-compound with sodium hydrosulphide in dilute alcohol) is boiled with sodium in alcohol and then mixed with o-chlorobenzylchloride to give, on working up, the final product of (5).