Oxalyl chloride → N-[(2-chloro-6-methylphenyl)carbonyl]-4-[1,3-dimethy-2,4-dioxo-6-(trifluoromethyl)-5-pyrimidinyl]-L-phenylalanine methyl ester

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Reaction Steps

A solution of 2-chloro-6-methylbenzoic acid (190 mg, 1.14 mmol) in dichloromethane (7 mL) containing DMF (4 drops) was treated with oxalyl chloride (0.42 mL, 4.8 mmol) and the mixture was stirred for 2 h. The mixture was concentrated, azeotroping with toluene to remove traces of oxalyl chloride and the residue was used directly in the next step. A mixture of the above prepared acid chloride, 4-(1,3-dimethyl-2,4-dioxo-6-(trifluoromethyl)-5-pyrimidinyl)-L-phenylalanine methyl ester hydrochloride salt (423 mg, 1.003 mmol) in dichloromethane (5 mL) was treated with DIPEA (0.625 mL, 4.46 mmol) and the resulting light brown solution was stirred for 3 days. The mixture was concentrated, diluted with ethyl acetate, washed with 1 N HCl and brine solution and was dried over magnesium sulfate. Filtration and evaporation afforded a residue, which was purified by silica gel chromatography using a Biotage column (40s) to give N-[(2-chloro-6-methylphenyl)carbonyl]-4-[1,3-dimethy-2,4-dioxo-6-(trifluoromethyl)-5-pyrimidinyl]-L-phenylalanine methyl ester as a white foam (179 mg, 33%). ES-HRMS m/e calcd for C25H23ClN3O5 (M+Na) 560.1171, found 560.1172.

Provenance & Evidence