Dichloromethane → 4-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidine

Participants

Reaction Conditions

Reaction Steps

4-Chloro-7H-pyrrolo[2,3-d]pyrimidine (9, 0.452 g, 2.94 mmol), cyclopropylmagnesium bromide (17, 31.4 mL, 0.50 M in tetrahydrofuran, 15.7 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) 1:1 complex with dichloromethane (0.240 g, 0.294 mmol) are combined with 15.4 mL of toluene. The reaction is heated at 60° C. overnight, then quenched with 1 M aqueous hydrochloric acid to pH 4 and filtered through a bed of celite. The layers of the filtrate are separated and the aqueous layer extracted with ethyl acetate. The combined organic layers are washed with brine, dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with ethyl acetate and hexane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (18, 0.465 g). MS (ESI) [M+H+]+=160.1. This is reacted similarly to steps 2 and 3 of Scheme 4 to provide the desired compound 19.

Provenance & Evidence