反应详情

To a solution of [3-({[2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carbonyl]-amino}-methyl)-benzyl]-carbamic acid tert-butyl ester (0.05 g, 0.111 mmol) in DCM (2 mL) at 0° C. is added TFA (0.013 mL. 0.111 mmol) and the mixture is stirred for 2.5 hours. The mixture is concentrated in vacuo. The residue is dissolved in THF (2 mL). Et3N (0.05 mL, 0.333 mmol) and methanesulfonyl chloride (0.010 mL, 0.133 mmol) are added and the mixture is stirred for 12 hours. The mixture is diluted with EtOAc (100 mL), washed with saturated aqueous NH4Cl (2×50 mL), dried with Na2SO4, filtered, and concentrated in vacuo. The residue is purified by flash chromatography eluting with 20%-80% EtOAc/heptane to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid 3-(methanesulfonylamino-methyl)-benzylamide (0.03 g, 64%) as a powder. MS: 429 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 2.65 (s, 3H), 2.86 (s, 3H), 4.18 (d, J=6.3 Hz, 2H), 4.50 (d, J=5.9 Hz, 2H), 7.27-7.45 (m, 3H), 7.62 (m, 2H), 8.13 (m, 1H), 8.28 (m, 1H), 8.90 (s, 1H), 9.25 (m, 1H); IC50=48.5 nM.

1. concentrationThe mixture is concentrated in vacuo
2. dissolutionThe residue is dissolved in THF (2 mL)
3. stirringthe mixture is stirred for 12 hours
4. washwashed with saturated aqueous NH4Cl (2×50 mL)
5. dry with materialdried with Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue is purified by flash chromatography
9. washeluting with 20%-80% EtOAc/heptane