Triethylamine → HCID 86643707, compound

Participants

Reaction Conditions

Reaction Steps

Thionyl chloride (15.7 mL, 215 mmol) and DMF (1 mL) were added to 4,6-dichloro-2-methylthio-pyrimidine-5-carboxylic acid (5.15 g, 21.5 mmol) obtained in Reference Example 4, and the mixture was stirred at 80° C. for 4 hours. The mixture was concentrated under reduced pressure, and the residue was dried for 12 hours under reduced pressure. The resulting residue was dissolved in THF (8 mL), and the mixture was stirred at room temperature for 1 hour after adding triethylamine (1.02 mL, 7.30 mmol), and a THF (10 mL) solution of (S)-1-tert-butoxycarbonyl-2-{N-[3-(4-methyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)phenyl]aminomethyl}pyrrolidine (1.37 mmol, 3.65 mmol) obtained in Step 5. The mixture was further stirred at 60° C. for 5.5 hours, and then for 6 hours under reflux. Water and ethyl acetate were added to the mixture to separate the organic layer. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was then purified by silica gel column chromatography to give (S)—N-(1-tert-butoxycarbonyl-pyrrolidin-2-ylmethyl)-4,6-dichloro-N-[3-(4-methyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)phenyl]-2-methylthiopyrimidine-5-carboxamide (1.30 g, 60%).

Provenance & Evidence