反应详情

温度

100 °C

To a solution of 5-hydrazinyl-2,4-dimethoxypyrimidine hydrochloride (Step 46.8) (413 mg, 2 mmol) in MeOH (5 mL) were added NaOAc (123 mg, 1.5 mmol), sulfamic acid (99 mg, 1 mmol) and 5-(4-chlorophenyl)-1-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-4-propionylpyrrolidine-2,3-dione (Step 60.1) (204 mg, 0.5 mmol) and the reaction mixture was stirred for 2.5 hr at 100° C. in the MW. The reaction mixture was added to a saturated aq. NaHCO3 solution and the aq. layer was extracted with EtOAc. Combined extracts were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography (hexane/EtOAc/MeOH 80:20:2 to 0:10:1) followed by preparative HPLC to afford, after crystallization from THF/Et2O, the title product (68 mg, 0.124 mmol, 25% yield) as a solid. tR: 1.03 min (LC-MS 2); ESI-MS: 521 [M+H]+ (LC-MS 2); Rf=0.36 (EtOAc/MeOH 9:1); 1H NMR (400 MHz, DMSO-d6) δ ppm 0.95 (t, J=7.8 Hz, 3H) 1.92 (s, 3H) 2.36 (m, 1H) 2.44 (m, 1H) 3.33 (s, 3H) 3.96 (s, 3H) 3.99 (s, 3H) 6.24 (m, 1H) 7.34 (m, 2H) 7.37-7.45 (m, 3H) 7.72 (s, 1H) 8.59 (s, 1H).

1. extractionthe aq. layer was extracted with EtOAc
2. washCombined extracts were washed with brine
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customThe crude material was purified by silica gel column chromatography (hexane/EtOAc/MeOH 80:20:2 to 0:10:1)
7. customto afford
8. customafter crystallization from THF/Et2O