Sodium Carbonate → HCID 46231381, compound

Participants

Reaction Conditions

Reaction Steps

A stream of nitrogen was passed through a solution of DMF/1-propanol (1 mL, 4 mL respectively), N1-(1-cyanocyclopropyl)-4-fluoro-N2-{(1S)-2,2,2-trifluoro-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl}-L-leucinamide from Example 1, Step 15, (150 mg), 1-(6-chloropyridin-3-yl)cyclopropanecarboxamide from Step 5 (74 mg) and 2 M Na2CO3 (400 μL) for 15 minutes followed by the addition of palladium acetate (II), complex (4:1) with triphenylphosphine (16 mg). The mixture was warmed to 80° C. for 8 hours under nitrogen. The mixture was cooled to room temperature, poured into ice (20 g) and saturated aqueous sodium bicarbonate (20 mL) and extracted with ethyl acetate (3×60 mL). The combined extracts were washed with brine and dried with magnesium sulfate. Removal of the solvent left a residue that was purified by chromatography on SiO2 (Combiflash) using ethyl acetate and hexanes (60% for 10 minutes, then 60 to 100% for 30 minutes) as eluants, followed by a swish using diethyl ether and hexanes to yield the title compound.

Provenance & Evidence