1,2-Dichloroethane → 1-(3-Fluoro-4-(5-(1-phenylcyclobutyl)thiazolo[5,4-b]pyridin-2-yl)benzyl)azetidine-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A solution of N,Ndimethylacetamide (0.320 mL, 3.46 mmol) in 30 mL anhyd. 1,2-DCE in a 3-neck flask under argon fitted with addition funnel was cooled to −17° C. with ice/salt. Trifluoromethanesulfonic anhydride (0.679 mL, 4.04 mmol) was added over 2 min by syringe, and the reaction mixture became yellow and the temperature rose to −13° C. After 5 min, a solution of 2,6-di-tert-butylpyridine (0.893 mL, 4.04 mmol) and 2-(2-fluoro-4-methylphenyl)-5-(1-phenylvinyl)thiazolo[5,4-b]pyridine (1.00 g, 2.89 mmol) in 15 mL DCE was added slowly dropwise via addition funnel over 10 min. The reaction was fitted with a water-cooled reflux condenser and placed in a 110° C. oil bath. After 1 h, the reaction mixture was allowed to cool to ambient temperature overnight. 45 mL water was added and the reaction mixture reheated to 110° C. After 7 h, the reaction mixture was cooled, layers separated, and the aqueous layer was extracted with DCM. The combined organics were dried over sodium sulfate, filtered, and concentrated. The crude material was adsorbed onto 5 g silica gel and purify by silica gel chromatography, 0-100% EA/hexanes to give a yellow solid containing the desired product. This was further purified by trituration with diethyl ether to give 3-(2-(2-fluoro-4-methylphenyl)-thiazolo[5,4-b]pyridine-5-yl)-3-phenylcyclobutanone as a light yellow solid. MS (ESI) m/z: calculated: 388.1; Observed: 389.1 (M++1).

Provenance & Evidence