Ammonium Chloride → 1-(4-(2-(3-Phenoxy-5-(thieno[3,2-b]pyridin-7-ylthio)pyridin-2-ylamino)thiazol-4-yl)piperidin-1-yl)ethanone dihydrochloride

Participants

Reaction Steps

A mixture of methyl 3-(6-(4-(1-acetylpiperidin-4-yl)thiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)propanoate (20.2 g, 39.3 mmol) and 7-chlorothieno[3,2-b]pyridine (7.34 g, 43.3 mmol) in DMSO (500 mL) was purged with nitrogen for 30 minutes and then KOtBu (13.9 g, 118.0 mmol) was added and the reaction was stirred at ambient temperature for 2 hrs. The mixture was poured into saturated aqueous NH4Cl (1 L) and extracted with EtOAc (1 L). The organics were washed with water (3×500 mL), dried over Na2SO4 and concentrated to a residue that was purified on silica eluting with 3-5% MeOH/EtOAc. The purified free base was dissolved in CH2Cl2 (300 mL) and 1N HCl in Et2O (300 mL) was added the slurry was concentrated to dryness to afford 1-(4-(2-(3-phenoxy-5-(thieno[3,2-b]pyridin-7-ylthio)pyridin-2-ylamino)thiazol-4-yl)piperidin-1-yl)ethanone dihydrochloride (19.5 g, 78%) as a yellow solid which was dried in a high vacuum oven at 45° C. overnight. 1H NMR (d6-DMSO) δ 8.65 (d, 1H), 8.48 (d, 1H), 8.46 (d, 1H), 7.77 (d, 1H), 7.54 (d, 1H), 7.41 (m, 2H), 7.18 (m, 4H), 6.82 (s, 1H), 4.43 (m, 1H), 3.88 (m, 1H), 3.14 (m, 1H), 2.89 (m, 1H), 2.64 (m, 1H), 2.01 (s, 3H), 1.96 (m, 2H), 1.58 (m, 1H), 1.45 (m, 1H). Mass spectrum (apci) m/z=560.4 (M+H-2HCl).

Provenance & Evidence