反应详情

A mixture of 2-(3,5-difluoro-phenyl)-pyrimidine-5-carboxylic acid (118 mg, 0.5 mmol, prepared according to the general procedure described in Example 2, steps 1 and 2) and O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium hexafluorophosphate (190 mg, 0.5 mmol) in dry DMF (5 mL) is treated with diisopropylethylamine (0.09 mL) and stirred at room temperature for 30 min. A solution of 3-methylsulfamoylbenzylamine (150 mg, 0.75 mmol.) in dry DMF (1 mL) is added and the mixture stirred at room temperature for 24 hours. The solvent is removed and the residue is partitioned between EtOAc and water. The organic phase is separated and washed with saturated NaHCO3, water and brine, dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by column chromatography eluting with 30% EtOAc in DCM to afford 2-(3,5-difluorophenyl)-pyrimidine-5-carboxylic acid 3-methylsulfamoyl-benzylamide (125 mg, 62%) as a solid. MS: 419 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 2.41 (d, 3H), 4.64 (d, 2H), 7.43-7.75 (m, 5H), 7.80 (s, 1H), 8.05 (d, 2H), 9.37 (s, 2H), 9.60 (t, 1H); IC50=49 nM.

1. customprepared
2. stirringthe mixture stirred at room temperature for 24 hours
3. customThe solvent is removed
4. customthe residue is partitioned between EtOAc and water
5. customThe organic phase is separated
6. washwashed with saturated NaHCO3, water and brine
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe residue is purified by column chromatography
11. washeluting with 30% EtOAc in DCM