反应详情

A solution of 2-(3-fluorophenyl)-4-methylpyrimidine-5-carboxylic acid (116 mg) and HATU (190 mg) in dry DMF is treated with DIPEA (0.09 mL) and stirred at rt for 40 min. 1-Amino-5-fluoro-1H-indole-3-sulfonic acid dimethylamide (192 mg) is added and the mixture is stirred at rt for 24 h. The mixture is concentrated in vacuo. The residue is dissolved in EtOAc, washed with 2 N aqueous NaOH, water and brine, dried (MgSO4) and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 30% EtOAc/heptane to afford 2-(3-fluorophenyl)-4-methylpyrimidine-5-carboxylic acid-(3-dimethylsulfamoyl-5-fluoroindol-1-yl)amide (85 mg, 40%) as a solid. MS: 472 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 2.68 (s, 6H), 2.79 (s, 3H), 7.25-7.35 (m, 1H), 7.45-7.55 (m, 1H), 7.57-7.80 (m, 3H), 8.20 (d, 1H), 8.35 (s, 1H), 8.47 (s, 2H), 9.28 (s, 1H), 12.40 (s, 1H).

1. stirringthe mixture is stirred at rt for 24 h
2. concentrationThe mixture is concentrated in vacuo
3. dissolutionThe residue is dissolved in EtOAc
4. washwashed with 2 N aqueous NaOH, water and brine
5. dry with materialdried (MgSO4)
6. concentrationconcentrated in vacuo
7. customThe residue is purified by silica gel chromatography
8. washeluting with 30% EtOAc/heptane