反应详情

A mixture of 5-(2-(4-chlorophenyl)-4-hydroxy-5-oxo-3-propionyl-2,5-dihydro-1H-pyrrol-1-yl)-1,3-dimethylpyridin-2(1H)-one (Step 147.1) (1.5 g, 3.88 mmol), hydrazine monohydrate (0.942 mL, 19.39 mmol), ethanol (8 mL) and toluene (8 mL) was stirred for 18 h at reflux. The reaction mixture was concentrated, diluted with acetic acid (50 mL), stirred for 1 h at reflux, diluted with CH2Cl2/saturated aqueous solution of NaHCO3, and extracted twice with CH2Cl2. The combine organic extracts were washed with water and brine, dried (Na2SO4) and concentrated. The residue was purified by silica gel column chromatography (CH2Cl2/MeOH 7.5%) and subsequent trituration of the resulting product in diethyl ether to afford 961 mg of the title compound as a yellow solid. tR: 0.82 min (LC-MS 2); ESI-MS: 383.1 [M+H]+ (LC-MS 2); Rf=0.19 (NH3 1%/CH2Cl2/MeOH 5%); 1H NMR (400 MHz, DMSO-d6) δ ppm 0.90 (t, J=7.64 Hz, 3H) 1.94 (s, 3H) 2.35-2.47 (m, 2H) 3.38 (s, 3H) 6.15 (s, 1H) 7.25 (d, J=8.44 Hz, 2H) 7.31-7.51 (m, 3H) 7.73 (d, J=2.69 Hz, 1H) 13.41 (br. s., 1H).

1. temperatureat reflux
2. concentrationThe reaction mixture was concentrated
3. additiondiluted with acetic acid (50 mL)
4. stirringstirred for 1 h
5. temperatureat reflux
6. additiondiluted with CH2Cl2/saturated aqueous solution of NaHCO3
7. extractionextracted twice with CH2Cl2
8. washThe combine organic extracts were washed with water and brine
9. dry with materialdried (Na2SO4)
10. concentrationconcentrated
11. customThe residue was purified by silica gel column chromatography (CH2Cl2/MeOH 7.5%) and subsequent trituration of the resulting product in diethyl ether