Triethylamine → N-methoxy-N-methyl-2-(methylthio)pyrimidine-4-carboxamide

Participants

Reaction Steps

A mixture of 2-(methylthio)pyrimidine-4-carboxylic acid (1-1, prepared according to Kim, C.-H., et al J. Med. Chem. 1986, 29, 1374–1380 and McOmie, W. J. Chem. Soc. 1953, 3129, 2.00 g, 11.8 mmol, 1 equiv), N,O-dimethylhydroxylamine hydrochloride (3.44 g, 35.3 mmol, 3.00 equiv), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (3.38 g, 17.6 mmol, 1.50 equiv), 1-hydroxy-7-azabenzotriazole (2.40 g, 17.6 mmol, 1.50 equiv), and triethylamine (6.55 mL, 47.0 mmol, 4.00 equiv) in DMF (40 mL) was stirred for 20 hours. The reaction mixture was partitioned between a 1:1 mixture of brine and saturated aqueous sodium carbonate solution (100 mL) and ethyl acetate (2×50 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (hexane initially, grading to 40% hexane in ethyl acetate) to give N-methoxy-N-methyl-2-(methylthio)pyrimidine-4-carboxamide (1-2) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 8.63 (d, 1H, J=4.9 Hz), 7.13 (br s, 1H), 3.74 (br s, 3H), 3.36 (br s, 3H), 2.59 (s, 3H).

Provenance & Evidence