反应详情

温度

67.5 °C

To a stirred solution 3-hydrazino-N-methoxy-4-methyl-benzamide 2 (116 mg, estimated 0.14 mmol) in EtOH (10 ml) was added 2-(3-iodo-benzoyl)-3-phenylamino-acrylonitrile 3 (59 mg, 0.14 mmol, preparation: International Patent Application Publication No. WO 02/57101 A1, pg. 84) and mixture was heated (bath T=65-70° C.) for 4 hr, when additional 3-hydrazino-N-methoxy-4-methyl-benzamide 2 (80 mg, 0.11 mmol) was added and the mixture was heated at the same temperature for 27 hr. It was cooled to room temperature, concentrated and redissolved in EtOAc before it was washed with water and brine, dried over Na2SO4, concentrated to give a crude semisolid. The mixture was then purified by flash chromatography, eluting with 1:1 EtOAc/hexanes to remove impurities then 100% EtOAc give 3-[5-amino-4-(3-iodo-benzoyl)-pyrazol-1-yl]-N-methoxy-4-methyl-benzamide 4 as an off-white solid (38 mg, 0.08 mmol, 55%). HPLC (6 minute gradient) tR 3.49 min; MS m/z 476.96 [M+H]+; 1H NMR (CD3OD, 300 MHz) δ 8.10 (s, 1 H), 7.95 (d, J=8.0, 1 H), 7.88 (d, J=8.0, 1 H), 7.82 (m, 2 H), 7.78 (s, 1 H), 7.58 (d, J=8.0, 1 H), 7.33 (t, J=7.8, 1 H), 5.02 (s. 3 H), 2.33 (s, 3 H) ppm; 13C NMR (DMSO-d6, 125 MHz.) δ 189.3, 154.3, 143.5, 143.3, 142.0, 138.3, 137.4, 133.5, 132.9, 132.0, 130.4, 128.8, 128.4, 104.8, 95.4, 64.8, 18.2 ppm.

1. custom59 mg, 0.14 mmol, preparation
2. temperaturethe mixture was heated at the same temperature for 27 hr
3. temperatureIt was cooled to room temperature
4. concentrationconcentrated
5. dissolutionredissolved in EtOAc before it
6. washwas washed with water and brine
7. dry with materialdried over Na2SO4
8. concentrationconcentrated
9. customto give a crude semisolid
10. customThe mixture was then purified by flash chromatography
11. washeluting with 1:1 EtOAc/hexanes
12. customto remove impurities