Sodium Bicarbonate → N-(3,6'-Dichloro-[2,4']bipyridinyl-3'-yl)-N-methyl-3,5-bis-trifluoromethyl-benzamide

Participants

Reaction Steps

To a solution of 3-chloro-2-iodopyridine (94.2 mg, 393 μmol, CAS RN 77332-89-9) in THF (3 mL) was added isopropylmagnesium chloride (2M solution in THF, 197 μl, 393 μmol) at −40° C. and the reaction mixture stirred for 20 minutes at this temperature. Freshly prepared ZnCl2 solution (1M in THF, 1.57 mL, 1.57 mmol) was added at −40° C. The reaction mixture was allowed to warm to room temperature and was stirred for 90 minutes. A solution of N-(6-chloro-4-iodo-pyridin-3-yl)-N-methyl-3,5-bis-trifluoromethyl-benzamide (200 mg, 393 μmol, Ex. 72, intermediate) in THF (3 mL) and tetrakis(triphenylphosphine)palladium(0) (22.7 mg, 19.7 μmol) was added. The reaction mixture was stirred for 1 hour at reflux. The reaction mixture was poured on 30 mL 10% aqueous NaHCO3 solution and 30 mL EtOAc. The layers were separated and the aqueous layer was extracted a second time with 30 mL EtOAc. The combined organic layers were washed with 30 mL brine, dried over MgSO4, filtered and concentrated under vacuum. The compound was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:EtOAc (100:0 to 50:50). The product was further purified by preparative HPLC (phenomenex gemini column) with a gradient of acetonitrile:water (50:50 to 95:5). Colorless foam (85 mg, 44%). MS (ESI): m/z=494.025 [M+H]+.

Provenance & Evidence