Methanol → HCID 68636738, compound

Participants

Reaction Conditions

Reaction Steps

1-(3-Fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenyl)ethanone (0.48 g, 1.2 mmol) was added to a solution of (R)-(+)-2-methyl-2-propanesulfinamide ((0.150 g, 1.2 mmol), titanium (iv) ethoxide (0.510 mL, 2.48 mmol) in THF (5 mL). The reaction mixture was heated to 70° C. for 2 h at which point additional (R)-(+)-2-methyl-2-propanesulfinamide (0.150 g, 1.2 mmol) and titanium (iv) ethoxide (0.51 mL, 2.48 mmol) were added and the reaction mixture was allowed to stir for 18 h at 70° C. The reaction mixture was cooled to ambient temperature and then to −50° C. To the reaction mixture was added dropwise 1 M solution of L-Selectride (3.7 mL, 3.7 mmol) also at −50° C., and allowed to stir for 5 h at −50° C. The reaction mixture was warmed to 0° C. and MeOH was added dropwise until gas evolution was no longer observed. The crude reaction mixture was poured into an equal volume of brine while being stirred rapidly. The resulting suspension was filtered through a plug of celite, the cake rinsed with EtOAc and MeOH. The filtrate was reduced in vacuo, the residue diluted with EtOAc, extracted with brine and dried over MgSO4. The crude reaction mixture was concentrated in vacuo and purified by silica gel chromatography to afford (S)-N-(1-(3-fluoro-4-(5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridin-2-yl)phenyl)-ethyl)-2-methylpropane-2-sulfinamide. MS (ESI) m/z: calculated: 493.2; Observed: 494.0 (M++1).

Provenance & Evidence