(Diethylamino)sulfur trifluoride → HCID 68456380, compound

Participants

Reaction Steps

A solution of (7S,7aS)-2-chloro-4-(7-hydroxy-3-oxotetrahydropyrrolo[1,2-c]imidazol-2-yl)-3-methylbenzonitrile (WO 03/096980) (30 mg, 0.103 mmol) in dry dichloromethane (1.0 mL) was cooled to −65° C., treated with DAST (26 μL, 0.21 mmol) and stirred for 17 h, allowing the temperature to warm to rt. The reaction mixture was then cooled to 0° C., quenched with 10% sodium carbonate (0.5 mL) and extracted with CH2Cl2 (2×10 mL). The organic phase was washed with H2O (0.5 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The syrup was combined with a previous batch (5.4 mg) and chromatographed 3×(silica gel; EtOAc/hexane gradient then CH3OH/CH2Cl2 gradient) to yield the title compound (14.5 mg, 47.9%). HPLC: 99.1% at 2.04 min (retention time) (Conditions: YMC S-5 C-18 (4.6×50 mm), eluting with 0-100% B, 4 min gradient. (A=90% H2O-10% CH3CN-0.1% TFA and B=10% H2O-90% CH3CN-0.1% TFA); Flow rate at 4 mL/min. UV detection at 220 nm). Chiral HPLC: retention time=20.8 min (100%); Conditions: OD (4.6×250 mm); Eluted with 20% isopropanol in heptane for 60 min at 1 mL/min. MS (ES+): m/z 294 [M+H]+.

Provenance & Evidence