反应详情

To a solution of 2-chloro-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-1-methyl-5-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrole-3-carboxamide (125 mg, 0.22 mmol) in tetrahydrofuran (1.1 ml) and methanol (1.1 ml) at 25° C. was added hydrazine (0.06 ml, 1.76 mmol) dropwise. After 12 h the solution was concentrated, dry loaded onto silica and purified by column chromatography (2% MeOH in DCM (1% NH4OH)). The free base was transferred to the HCl salt by addition of excess 2M HCl in Ether (20 ml) to the residue in DCM (40 ml) affording the HCl salt of N-((1S)-2-amino-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-2-chloro-1-methyl-5-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrole-3-carboxamide (70 mg, 0.13 mmol, 57% yield) as a white solid: LCMS (ES) m/z=440, 442 (M, M+2)+, 1H NMR (400 MHz, DMSO-d6) δ ppm 8.17 (d, J=9.09 Hz, 1 H) 8.08 (br. s., 2 H) 7.69 (d, J=8.08 Hz, 1 H) 7.58 (br. s., 1 H) 7.57 (d, J=2.02 Hz, 1 H) 7.40-7.43 (m, 1 H) 7.02 (s, 1 H) 6.48 (d, J=2.02 Hz, 1 H) 4.50-4.57 (m, 1 H) 3.78 (s, 3 H) 3.44 (s, 3 H) 2.98-3.07 (m, 4 H).

1. concentrationAfter 12 h the solution was concentrated
2. customdry loaded onto silica
3. custompurified by column chromatography (2% MeOH in DCM (1% NH4OH))
4. additionThe free base was transferred to the HCl salt by addition of excess 2M HCl in Ether (20 ml) to the residue in DCM (40 ml)