Water → HCID 135921415, compound

Participants

Reaction Conditions

Reaction Steps

(S)-tert-Butyl 3-(2-(2-methoxyphenyl)quinazolin-4-ylamino)pyrrolidine-1-carboxylate (0.259 g, 0.616 mmol) (prepared by methods analogous to those described in Synthesis 2) was dissolved in DMF (6.16 mL) and cooled to −30° C. NaH (60% dispersion in mineral oil, 0.041 mg, 0.678 mmol) was added and the mixture was stirred at −30° C. for 15 minutes. The mixture was cooled to −78° C. and iodomethane (0.046 mL, 0.727 mmol) was added dropwise. The solution was warmed to room temperature over 2 hours. Water (5 mL) was added and the aqueous phase was extracted with dichloromethane (3×20 mL). The combined organic phases were dried (MgSO4) and concentrated in vacuo. The residue was purified by ion exchange chromatography on SCX-2 Isolute acidic resin (2 g), eluting with methanol and then 1 M ammonia in methanol. The solvents were removed in vacuo and the residue was dissolved in dichloromethane (1.3 mL) and 1 M boron tribromide in dichloromethane (1.3 mL). The solution was stirred at room temperature for 18 hours. Methanol (5 mL) was added and the mixture was purified by ion exchange chromatography on SCX-2 Isolute acidic resin (2 g), eluting with methanol and then 1 M ammonia in methanol. Further purification by silica column chromatography, eluting with a gradient from 3% to 30% methanol in dichloromethane, gave the title compound as a yellow solid (0.028 g, 66%).

Provenance & Evidence