(R)-tert-butyl 1-(3-butyramido-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate → (R)-N-(4-(3-aminopiperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)butyramide
Reaction equation
[C:1]([NH:6][C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([Cl:30])[C:14]=2[N:16]2[CH2:21][CH2:20][CH2:19][C@@H:18]([NH:22]C(=O)OC(C)(C)C)[CH2:17]2)[NH:9][CH:8]=1)(=[O:5])[CH2:2][CH2:3][CH3:4]>C(O)(C(F)(F)F)=O>[NH2:22][C@@H:18]1[CH2:19][CH2:20][CH2:21][N:16]([C:14]2[C:13]([Cl:30])=[CH:12][N:11]=[C:10]3[NH:9][CH:8]=[C:7]([NH:6][C:1](=[O:5])[CH2:2][CH2:3][CH3:4])[C:15]=23)[CH2:17]1Participants
3
Procedure
(R)-tert-Butyl 1-(3-butyramido-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (221 mg, 0.507 mmol) was stirred in TFA (3 mL) at room temperature for 1.5 hours. The solvent was evaporated in vacuo, and the residue purified by reverse phase chromatography (Biotage SP4, C-18 12M+, 2-50% CH3CN/water, 16CV). The isolated product was taken up in a minimal volume of methanol and added to a stirred solution of 2N HCl-Et2O. The salt formed was collected by filtration, washed with acetonitrile and dried under vacuum to give (R)—N-(4-(3-aminopiperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)butyramide (153 mg, 74% yield) as a solid. 1H NMR (400 MHz, (CD3)2SO) δ 11.83 (br s, 1H), 9.32 (s, 1H), 8.35 (br s, 2H), 8.13 (s, 1H), 7.57 (s, 1H), 3.54-3.46 (m, 1H), 3.45-3.30 (m, 2H), 3.27-3.04 (m, 2H), 2.41-2.34 (m, 2H), 2.18-2.09 (m, 1H), 1.91-1.79 (m, 1H), 1.72-1.59 (m, 3H), 1.59-1.39 (m, 1H), 0.96 (t, 3H). LCMS (APCI+) m/z 336.1, 338.1 (M+H)+, Retention time=2.38 minutes.