Angiotensin converting enzyme inhibiting cpds. - comprising a 2,3-di:hydro-1,3,4-thiadiazole, --1,3,4-oxadiazole or 1,3,4-triazole carboxylic acid

摘要

With glyoxylic acid, e.g. in an alkanol. (II) in which n = 1 may be prepd. by reacting (IV) with CH2=(X)COOH. In an example, a soln. of benzenecarbothioic acid hydrazide (2g) and benzyl glyoxylate (2.6g) in EtOH was stirred for 18 hrs. under N2. A stirred mixt. of N-(1-(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine (3.1g) and 1-hydroxybenzotriazole (1.7g) in CH2Cl2 (100 ml) was treated with a soln. of the prod. (6.85g) in CH2Cl2. A soln. of dicyclohexylcarbodiimide (2.26g) in CH2Cl2 (20 ml) was added over 20 mins. and the mixt. stirred for 2 days under N2. A soln. of the prod. obtd. (0.16g), pyrrolidine (0.16 ml) and 3A molecular sieves (0.2g) in acetonitrile (3.2 ml) was stirred for 3.5 hrs. A soln. of the prod. obtd. (0.26g) in EtOH was treated with 10% Pd/charcoal (0.1g) and stirred in a pressure vessel under hydrogen at 3 atmospheres for 3 days. The catalyst was filtered off and the filtrate evapd. The residue was triturated with ether to give (Ia), m.pt. 180.5-182 deg.C.