1,2,4-Thiadiazole-5-carboxylicacid,3-methyl-,methylester(9CI) synthesis

Yield:352356-71-9 11%

Reaction Conditions:

Stage #1: acetamide;chloro(chlorosulfanyl)methanone in toluene; for 2 h;Reflux;
Stage #2: methyl cyanoformate in toluene; for 4 h;Reflux;

Steps:

C.12 Scheme 12: Synthesis of methyl 3-methyl-l,2,4-thiadiazole-5-carboxylate 2.2n

Scheme 12: Synthesis of methyl 3-methyl-l,2,4-thiadiazole-5-carboxylate 2.2n A solution of 2.0n (500 mg, 8.46 mmol, 1 eq.), and 2.0n' (820 μ?,, 9.31 mmol, 1.2 eq.) in dry toluene (23 mL) was stirred at reflux for 2 hours. The solvent was then evaporated under reduced pressure and the residue was dissolved again in toluene (11.3 mL). 2.0n" (2.0 mL, 25.4 mmol, 3 eq.) was added to the solution and the resulting mixture was stirred at reflux for 4 hours. The solvent was evaporated and the obtained crude was purified by flash chromatography on silica gel (eluent: DCM 100%) to obtain the desired ester 2.2n (150 mg, 0.95 mmol, 11 %) as a brown oil. LCMS: P = 97 %, retention time = 1.8 min, (M+H)⁺: 159.

References:

WO2013/50424,2013,A1 Location in patent:Page/Page column 116-117