SummaryA new approach to 2-amino-6-(methoxycarbonyl)amino-4-( 1,2,3,6-tetrahydro-1 -pyridyl)pyrimidine 1 -oxide (3) is described. Methyl [ l-ethoxy-2-(ethoxycarbonyl)-ethylidenelcarbamate (5) reacted with guanidine to the pyrimidinecarbamate 6, which was successively transformed into methyl 2-amino-6-@-tolylsulfonyl)oxy-4-pyrimidinecarbamate (8). Oxidation of 8 led to the corresponding pyrimidine Noxide 9, a useful starting material to 3.In a series of reports, we recently described the synthesis of new 2-0x0-2H-[ 1,2,4]oxadiazolo [2,3-a]pyrimidine-7-carbamates 1 [ 11 [2] and the synthesis of the regioisomers 2-0x0-2 H-[ 1,2,4]oxadiazolo [2,3-c]pyrimidine-5-carbamates 2 [3], which both possess interesting cardiovascular properties. As a result of these investigations, l a (Ro 12-4713), a potent antihypertensive agent was chosen to undergo clinical trials. One of the main metabolites of Ro 12-4713 in animals as well as in man was found to be the 2-amino-6-(methoxycarbonyl)amino-4-( 1,2,3,6-tetrahydro-1 -pyridyl)pyrimidine 1 -oxide (3) [4].To secure 3 in quantities sufficient for its biological evaluation and for its further transformation into 2, it was necessary to develop an alternative to the previously reported routes [l] [3].We describe here a new synthesis of 2,4,6-trisubstituted pyrimidine nucleus which allows introduction of the carbamate moiety in position 4 at an early stage, whereas the substitution with tetrahydropyridyl in position 6 is performed at the last step.Treatment of ethyl cyanoacetate with HC1 in EtOH gave the 3-amino-3-ethoxyacrylate hydrochloride 4. Transformation of 4 into the methyl carbamate 5 (mixture I )