反应详情

TFA (500 μL, 6.490 mmol) was added to a stirred solution of tert-butyl 3-[4-[5-[bis(tert-butoxycarbonyl)amino]-6-(3-phenylisoxazol-5-yl)pyrazin-2-yl]phenyl]sulfonylpiperidine-1-carboxylate (144 mg, 0.1890 mmol) in DCM (5 mL) and the reaction stirred at ambient temperature over night. The solvent was removed in vacuo and the residue azeotroped with DCM (×2) and ether (×2). The residue was passed through a 5 g SCX-2 cartridge and washed with MeOH/DCM mixtures. The product was eluted by washing the cartridge with 2M NH3 in MeOH/DCM mixtures. The solvent was removed in vacuo. The residue was tritruated from MeOH and the precipitate isolated by filtration to give 3-(3-phenylisoxazol-5-yl)-5-(4-(piperidin-3-ylsulfonyl)phenyl)pyrazin-2-amine Compound I-1 as an orange solid (39 mg, 45% Yield). H NMR (400.0 MHz, DMSO-d6) δ 8.95 (s, 1H), 8.39 (d, 2H), 8.05-8.02 (m, 2H), 7.92 (d, 2H), 7.80 (s, 1H), 7.61-7.55 (m, 3H), 7.21 (br s, 1H), 3.32-3.30 (m, 1H), 3.24-3.20 (m, 1H), 3.12-3.08 (m, 1H), 2.82-2.79 (m, 1H), 2.29-2.26 (m, 1H), 2.01-1.97 (m, 1H), 1.67-1.63 (m, 1H), 1.54-1.45 (m, 1H) and 1.37-1.31 (m, 1H) ppm; LC/MS m/z 462.1 [M+1]+.

1. customThe solvent was removed in vacuo
2. customthe residue azeotroped with DCM (×2) and ether (×2)
3. washwashed with MeOH/DCM
4. washThe product was eluted
5. washby washing the cartridge with 2M NH3 in MeOH/DCM mixtures
6. customThe solvent was removed in vacuo
7. customthe precipitate isolated by filtration