Triethylamine → (S)-{2-(4-Chlorobenzyl)-3-oxo-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-propyl}-carbamic acid tert-butyl ester

Participants

Reaction Steps

NEt3 (150 μL, 1.1 mmol) was added to a stirred suspension of 4-Piperazin-1-yl-7H-pyrrolo[2,3-d]pyrimidine dihydrochloride (100 mg, 0.36 mmol), (S)-2-(tert-Butoxycarbonylamino-methyl)-3-(4-chlorophenyl)-propionic acid (130 mg, 0.40 mmol), EDCI (83 mg, 0.44 mmol) and HOBt (59 mg, 0.44 mmol) in DMF (15 mL) at RT. Stirred at RT overnight. Poured into EtOAc (100 mL), washed with water (100 mL), 1N NaOH (50 mL), dried over Na2SO4, concentrated in vacuo, purified by column chromatography on silica (100% EtOAc) to give (S)-{2-(4-Chlorobenzyl)-3-oxo-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-propyl}-carbamic acid tert-butyl ester. LCMS (APCI+) m/z 499 [M+H]+; Rt: 2.70 minutes. This was taken up into DCM (50 mL) and stirred with TFA (5 mL) overnight. Poured into EtOAc (100 mL) and washed with 1N NaOH (2×100 mL), dried over Na2SO4 and concentrated in vacuo. Formed HCl salt (Et2O.HCl, 2M in diethyl ether) to give (S)-2-Aminomethyl-3-(4-chlorophenyl)-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-propan-1-one dihydrochloride (100 mg, 59%.) LCMS (APCI+) m/z 399 [M+H]+; Rt: 1.82 min. [Free base: 1H NMR (CDCl3, 400 MHz) δ 9.97 (1H, br.s), 8.32 (1H, s), 7.24 (2H, d, J 7.4 Hz), 7.13 (2H, d, J 7.4 Hz), 7.09 (1H, d, J 2.4 Hz), 6.45 (1H, d, J 2.3 Hz), 4.00-3.68 (5H, m), 3.60-3.53 (1H, m), 3.46-3.40 (1H, m), 3.33-3.27 (1H, m), 3.16-3.05 (2H, m), 2.92-2.83 (2H, m), 2.77 (1H, dd, J 13.3 and 5.5 Hz.)]

Provenance & Evidence