GB619915A - New pyrimidine derivatives - Google Patents

Abstract

5-Nitropyrimidines of the formula <FORM:0619915/IV(b)/1> where either B or D is the group -NH.CRR1. COOR11 (where R and R1 may be hydrogen, hydrocarbon, or substituted hydrocarbon, and one of them may be -COOR11; R11 is a hydrocarbon radical), and the other group may be hydrogen, halogen, amino or alkyl, and A may be any of these four groups or -NH.CRR1.COOR11, are prepared by condensing an a -aminoester, NH2.CRR1.COOR11 with a 5-nitropyrimidine of the formula <FORM:0619915/IV(b)/2> where either Y or Z is halogen, and the other group, and X, may be hydrogen, halogen, amino, or alkyl. The condensation is carried out by mixing in a solvent, e.g. methanol. The aminoester is conveniently generated from its hydrochloride by the action of aqueous or alcoholic alkali immediately prior to the reaction; one or two molecules of the aminoester may be used. Preferred starting materials are 4-methyl-6-chloro-2-amino-5-nitropyrimidine, and ethyl a -aminopropionate, ethyl aminoisobutyrate, ethyl a -amino-b -ethoxypropionate and ethyl a -amino-b -phenylpropionate. Products which contain one or two halogen atoms in positions 2, 4 or 6 are reacted with a primary or secondary amine to give the corresponding amino-derivative. In addition, the substituted 5-nitropyrimidines are reduced, preferably with hydrogen and a Raney nickel catalyst, to give derivatives of 6-hydroxy-7 : 8-dihydropteridins. In example 1, glycine methyl ester in methanol at 0 DEG C. is added to 2 : 6-dichloro-5-nitropyrimidine to give 2-chloro-5-nitro - 6 - carbomethoxymethylaminopyrimidine which, with a solution of ammonia in methanol, gives 2-amino-5-nitro-6-carbonethoxymethylaminopyrimidine; reduction of the 2-chloro-5-nitro - 6 - carbomethoxymethylaminopyrimidine with hydrogen and Raney nickel gives 2-chloro-6-hydroxydihydropteridin. In example 2, glycine ethyl ester is added to 2 : 6-dichloro-5-nitro-4-methylpyrimidine to give 2-chloro-5-nitro - 4 - methyl - 6 - carboethoxymethylamino - pyrimidine which, with ammonia, gives the 2 - amino compound; 2 - chloro - 4 - methyl - 6 - hydroxydihydropteridin is obtained on reduction of the 2-chloro-5-nitro-4-methyl-6-carboethoxymethylaminopyrimidine. In example 3, 2 - chloro - 5 - nitro - 4 - methyl - 6 - carbomethoxy - methylaminopyrimidine is prepared from the 2 : 6-dichloro compound and glycine methyl ester. In a further seven examples, the pyrimidines already mentioned, and also 4 : 6-dichloro - 5 - nitro - 2 - methylpyrimidine are condensed with glycine esters or ethyl aminomalonate, the products reacted with ammonia, diethylamine or b -diethylaminoethylamine, and the corresponding dihydropteridins also prepared by reduction of the pyrimidines. 4-Methyl-6-chloro-2-amino-5-nitropyrimidine is prepared from 4-methyl-6-hydroxy-2-amino-5-nitropyrimidine by the action of phosphorus oxychloride.