Sodium Carbonate → HCID 86594563, compound

Participants

Reaction Steps

A mixture of N2-(4-bromoisothiazol-5-yl)-N1-(cyanomethyl)leucinamide (91 mg, 0.27 mmol), 4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenylboronic acid (100 mg, 0.33 mmol, prepared as described in Example 1), PdCl2(dppf) (5 mg, 0.006 mmol) and 2.0 M Na2CO3 aqueous solution (0.17 mL, 0.34 mmol) were heated to 85° C. in N,N-dimethylformamide (0.80 mL) under a nitrogen atmosphere for a total of 8 h. During this period additional catalyst (5 mg) was introduced at the 2 h, 4 h and 6 h time points. The reaction mixture was then cooled to rt, diluted with water and extracted with ethyl acetate (3×). The combined extracts were washed with saturated sodium chloride solution, dried (Na2SO4) and concentrated. Flash chromatography of the residue on silica eluting with a mixture of acetone and benzene (1:4) afforded 63 mg of N1-(cyanomethyl)-N2-[4-(4-(tert-butoxycarbonyl)piperazin-1-ylphenyl)isothiazol-5-yl]leucinamide as a faint-tan foam.

Provenance & Evidence