反应详情

DIPEA (120 μL, 0.70 mmol) was added to a suspension of 7-Benzenesulfonyl-5-methyl-4-piperazin-1-yl-7H-pyrrolo[2,3-d]pyrimidine dihydrochloride (50 mg, 0.12 mmol) and (S)-2-(tert-Butoxycarbonylamino-methyl)-3-(4-chlorophenyl)-propionic acid (40 mg, 0.13 mmol) in DCM (10 mL) at room temperature. Then, HBTU (48 mg, 0.13 mmol) was added and the reaction stirred at room temperature overnight. MeOH (5 mL) and 3M LiOH (1.2 mL) were added and the mixture stirred and heated at 50° C. for 2 hours. The mixture was diluted with saturated aqueous NaHCO3 (10 mL), extracted into DCM, dried over Na2SO4 and concentrated in vacuo. The crude mixture was purified by column chromatography on silica (50% EtOAc/hexanes) to give (S)-{2-(4-Chlorobenzyl)-3-[4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-oxo-propyl}-carbamic acid tert-butyl ester. LCMS (APCI+) m/z 253 [M+H]+; Rt: 2.85 min. This was taken up into MeOH (10 mL) and treated with anhydrous HCl (4M in dioxane, 20 mL.) The solution was stirred at room temperature overnight and concentrated in vacuo to give (S)-2-Aminomethyl-3-(4-chlorophenyl)-1-[4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-propan-1-one dihydrochloride (21 mg, 37%.) LCMS (APCI+) m/z 413 [M+H]+; Rt: 1.82 min.

1. stirringthe mixture stirred
2. temperatureheated at 50° C. for 2 hours
3. extractionextracted into DCM
4. dry with materialdried over Na2SO4
5. concentrationconcentrated in vacuo
6. customThe crude mixture was purified by column chromatography on silica (50% EtOAc/hexanes)