反应详情

A mixture of 3.02 g (6.33 mmol) 5-methyl 1-(4-nitrophenyl) (6S)-6-(3,4-difluorophenyl)-4-(methoxymethyl)-2-oxo-3,6-dihydro-1,5(2H)-pyrimidinedicarboxylate, 1.50 g (5.80 mmol) of 3-(4-(3-nitrophenyl)-3,6-dihydro-1(2H)-pyridinyl)-1-propanamine, 7.94 g (75.5 mmol) of K2CO3 and 1.00 mL of methanol in 200 mL dichloromethane (under argon) was stirred at room temperature for 1 hour. The reaction mixture was filtered and concentrated in vacuo. The residue was dissolved in 100 mL of ethyl acetate and washed 3×50 mL of 5% aqueous NaOH solution, the organic layer was dried (MgSO4) and concentrated in vacuo. The residue was dissolved in 100 mL of anhydrous ethanol containing 0.50 g 10% Pd/C and the reaction mixture was stirred under a hydrogen balloon for 24 hours. The reaction mixture was passed through a column of Celite 545 filtering agent, washed with ethanol, the filtrate was dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (silica, 9.5:0.5, dichloromethane:methanol+1% isopropyl amine) to afford 1.65 g (52.0% yield) of the desired product: 1H NMR (400 MHz, CDCl3) δ 7.80 (s, 1H), 7.22-7.02 (m, 2H), 6.95 (t, J=8.70 Hz, 1H), 6.63-6.44 (m, 4H), 4.56 (Abq, 2H), 3.62 (s, 3H), 3.33 (s, 3H), 3.32-3.20 (m, 4H), 2.96 (br s, 2H), 2.33 (t, J=7.50 Hz, 2H), 2.11-1.94 (m, 3H), 1.81-1.64 (m, 4H); ESMS m/e: 572.3 (M+H)+;

1. filtrationThe reaction mixture was filtered
2. concentrationconcentrated in vacuo
3. dissolutionThe residue was dissolved in 100 mL of ethyl acetate
4. washwashed 3×50 mL of 5% aqueous NaOH solution
5. dry with materialthe organic layer was dried (MgSO4)
6. concentrationconcentrated in vacuo
7. dissolutionThe residue was dissolved in 100 mL of anhydrous ethanol containing 0.50 g 10% Pd/C
8. stirringthe reaction mixture was stirred under a hydrogen balloon for 24 hours
9. washwashed with ethanol
10. dry with materialthe filtrate was dried (MgSO4)
11. concentrationconcentrated in vacuo
12. customThe residue was purified by column chromatography (silica, 9.5:0.5, dichloromethane:methanol+1% isopropyl amine)