反应详情

温度

90 °C

This procedure was based on the method described in Antonio Abad, Consuelo Agulló, Ana Carmen Cuñat, Cristina Vilanova Synthesis, 2005, 915. To a 10 mL round-bottomed flask was added 2-(2-(2-chloropyridin-4-yloxy)ethyl)-6-phenylpyridazin-3(2H)-one (0.10 g, 0.31 mmol), pyrrolidine-1-carboxamide (0.038 g, 0.34 mmol) (see John E. Barry, Manuel Finkelstein, Gudrun A. Hutchins and Sidney D. Ross Tetrahedron 1983, 39, 2151-2156 and Charles A. Weisel, Harry S. Mosher, and F. C. Whitmore J. Am. Chem. Soc. 1945, 67, 1055), p-dioxane (2.5 mL), H2O (0.0082 mL, 0.46 mmol) and sodium tert-butoxide (0.044 g, 0.46 mmol). The mixture was carefully evacuated and backfilled with N2. This was repeated 3 times. To the mixture was added 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.018 g, 0.031 mmol) and palladium(II) acetate (0.0034 g, 0.015 mmol). Once again the mixture was carefully evacuated and backfilled with N2. This was repeated 3 times. The mixture was then stirred at 90° C. After 17 h, the mixture was poured into aq. NaHCO3 (100 mL) and extracted with EtOAc(3×75 mL). The combined extracts were washed with water (100 mL) and brine (100 mL) and then dried (Na2SO4) and concentrated onto silica. Purification by silica gel chromatography (1.0 to 5.0% MeOH (2M in NH3)/CH2Cl2) afforded N-(4-(2-(6-oxo-3-phenylpyridazin-1(6H)-yl)ethoxy)pyridin-2-yl)pyrrolidine-1-carboxamide (0.015 g, 12% yield) as a yellow solid. MS (ESI, pos. ion.) m/z: 406 (MH+). Calc'd exact mass for C22H23N5O3: 405. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.77-1.86 (m, 4 H), 3.33-3.40 (m, 4 H), 4.46-4.55 (m, 4 H), 6.58 (dd, J=5.8, 2.4 Hz, 1 H), 7.07 (d, J=9.8 Hz, 1 H), 7.43-7.50 (m, 3H), 7.52 (d, J=2.3 Hz, 1 H), 7.84-7.89 (m, 2 H), 8.00 (d, J=5.7 Hz, 1 H), 8.05 (d, J=9.8 Hz, 1 H), 8.51 (s, 1 H).

1. customdescribed in Antonio Abad, Consuelo Agulló, Ana Carmen Cuñat, Cristina Vilanova Synthesis, 2005, 915
2. customThe mixture was carefully evacuated
3. customOnce again the mixture was carefully evacuated
4. additionthe mixture was poured into aq. NaHCO3 (100 mL)
5. extractionextracted with EtOAc(3×75 mL)
6. washThe combined extracts were washed with water (100 mL) and brine (100 mL)
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated onto silica
9. customPurification by silica gel chromatography (1.0 to 5.0% MeOH (2M in NH3)/CH2Cl2)