反应详情

A mixture of 2-(3-pyridyl)-4-methylpyrimidine-5-carboxylic acid (215 mg, 1 mmol, prepared according to the general procedure described in Example 42, steps 1 and 2) and O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium hexafluorophosphate (380 mg, 1 mmol) in dry DMF (12 mL) is treated with of diisopropylethylamine (0.18 mL) and stirred at room temperature for 30 min. 3-Methylsulfamoylbenzylamine hydrochloride (355 mg, 1.5 mmol) is added and the mixture is stirred at room temperature for 24 hours. The solvent is removed and the residue partitioned between EtOAc and saturated NaHCO3. The organic phase is separated, washed with water and brine, dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by column chromatography eluting with 2% MeOH in EtOAc to afford 2-(3-pyridyl)-4-methyl-pyrimidine-5-carboxylic-acid-3-methylsulfamoyl-benzylamide (180 mg, 45%) as a solid. MS: 398 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 2.43 (s, 3H), 2.65 (s, 3H), 4.60 (d, 2H), 7.57-7.71 (m, 4H), 7.79 (s, 1H), 8.68-8.72 (d, 1H), 8.72-8.78 (d, 1H), 8.93 (s, 1H), 9.34 (t, 1H), 9.53 (s, 1H).

1. customprepared
2. stirringthe mixture is stirred at room temperature for 24 hours
3. customThe solvent is removed
4. customthe residue partitioned between EtOAc and saturated NaHCO3
5. customThe organic phase is separated
6. washwashed with 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 2% MeOH in EtOAc