Triphenylphosphine → 1,1-dimethylethyl 3-(5-bromo-4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-azetidinecarboxylate

Participants

Reaction Steps

To a solution of 5-bromo-4-chloro-1H-pyrrolo[2,3-d]pyrimidine (400 mg, 1.721 mmol), 1,1-dimethylethyl 3-hydroxy-1-azetidinecarboxylate (894 mg, 5.16 mmol) and triphenylphosphine (903 mg, 3.44 mmol) in Tetrahydrofuran (THF) (10 mL) was added dropwise DEAD (545 μl, 3.44 mmol). The solution was let stir at room temp. After 1 hr the reaction observed 10% product and the reaction was heated at 60° C. After 1 hr observed 80% desired product. Additional 100 mg of the 5-bromo-4-chloro-1H-pyrrolo[2,3-d]pyrimidine was added and heating was continued. The reaction was concentrated then loaded on to a 25 g SNAP column with 0 to 35% EtOAc in Hexane gradient over 30 minutes to give 1,1-dimethylethyl 3-(5-bromo-4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-azetidinecarboxylate (624 mg, 94% yield) as a white solid. LC-MS (ES) m/z=386.9, 389.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 8.69 (s, 1H), 8.38 (s, 1H), 5.53-5.62 (m, 1H), 4.33 (d, J=8.34 Hz, 4H), 1.43 (s, 9H).

Provenance & Evidence