Sodium Bicarbonate → (5-chloropyridin-2-yl)(1H-imidazol-1-yl)methanone

Participants

Reaction Steps

A stock solution of (5-chloropyridin-2-yl)(1H-imidazol-1-yl)methanone was prepared by adding N,N′-carbonyldiimidazole (Aldrich; 278 mg, 1.72 mmol) to a solution of 5-chloropicolinic acid (Shao Yuan; 280 mg, 1.78 mmol) in THF (5.0 mL) and heating the reaction mixture to 60° C. for 2 h. (4S,6S)-4-(5-amino-2-fluorophenyl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (4i, 50 mg, 0.172 mmol) was added to a flask containing 0.55 mL (1.1 equiv.) of the (5-chloropyridin-2-yl)(1H-imidazol-1-yl)methanone stock solution. The reaction mixture was allowed to stir for 30 min at ambient temperature, after which a second aliquot of (5-chloropyridin-2-yl)(1H-imidazol-1-yl)methanone solution (0.55 mL, 1.1 equiv.) was added. After 16 hs, saturated aqueous NaHCO3 (50 mL) was added to the reaction mixture and the product was extracted with EtOAc (3×50 mL). The combined organic extracts were dried over MgSO4, concentrated, and purified by flash chromatography on silica gel (Gradient: 0%→50% EtOAc/hexane) to give 5-chloro-N-((4S,6S)-4-(5-(5-chloropicolinamido)-2-fluorophenyl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)picolinamide (85.3 mg, 0.150 mmol) as a colorless glass. MS m/z=570 M+. Calculated for C24H17Cl2F4N5O3: 570.3

Provenance & Evidence