Oxalyl chloride → HCID 58128704, compound

Participants

Reaction Steps

To a solution of 10 mL dichloromethane and 1 drop of DMF was added 150 mg of (S)-4-(4-fluoro-phenyl)-1-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid. To this mixture was added 70 μl oxalyl chloride. When the bubbling stopped another drop of oxalyl chloride was added but as no bubbling was observed the solution was stirred at room temperature for 30 minutes after which the solvent was removed in vacuo to afford crude (S)-4-(4-fluoro-phenyl)-1-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid chloride (not shown in Scheme H). This acid chloride was taken up in propionitrile and added to a solution of 125 mg 5-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-4-chloro-2-methyl-phenylamine, 3 ml propionitrile, and 0.1 ml di-iso-propylethylamine. The solution was stirred at room temperature for 18 hours, then diluted with ethyl acetate and aqueous pH 2 buffer. The layers were separated and the organic layer dried over Na2SO4, filtered and the solvent removed in vacuo to give (S)-4-(4-fluoro-phenyl)-1-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid{5-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-4-chloro-2-methyl-phenyl}-amide, which was used directly in the next step without further purification.

Provenance & Evidence