반응 #1499197

반응 방정식

(2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-5-yl}-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetate

5-bromo-1-methyl-3-(5-methylisoxazol-3-ylamino)pyridine-2(1H)-one

5-Bromo-1-methyl-3-(5-methylisoxazol-3-ylamino)pyridin-2(1H)-one

K3PO4

sodium acetate

→

291a

수율 60.1%

(4-{1-Methyl-5-[(5-methyl-1,2-oxazol-3-yl)amino]-6-oxo-1,6-dihydropyridin-3-yl}-2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-5-yl}pyridin-3-yl)methyl Acetate

수율 60.1%

용매

acetonitrile

water

반응 조건

후처리

1. 1
   기타A 50-mL round-bottomed flask equipped with a reflux condenser
2. 2
   기타flush
3. 3
   온도The reaction mixture was cooled to room temperature
4. 4
   여과filtered
5. 5
   농축The filtrate was concentrated under reduced pressure
6. 6
   기타The residue was partitioned between dichloromethane (20 mL) and water (10 mL)
7. 7
   기타The organic layer was separated
8. 8
   추출the water layer was extracted with dichloromethane (2×20 mL)
9. 9
   건조The combined organic layer was dried over Na2SO4
10. 10
    여과filtered
11. 11
    농축concentrated under reduced pressure
12. 12
    기타The dark residue was purified by silica-gel column chromatography
13. 13
    세척eluting with 30:1 dichloromethane/methanol

실험 절차

A 50-mL round-bottomed flask equipped with a reflux condenser was charged with (2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-5-yl}-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetate 230i (150 mg, 0.31 mmol), 5-bromo-1-methyl-3-(5-methylisoxazol-3-ylamino)pyridine-2(1H)-one 283a (88 mg, 0.31 mmol), PdCl2(dppf) (24 mg, 0.031 mmol), K3PO4 (131 mg, 0.62 mmol), sodium acetate (61 mg, 0.62 mmol), water (0.2 mL), and acetonitrile (10 mL). The system was subjected to three cycles of vacuum/argon flush and stirred at 100° C. for 3 h. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was partitioned between dichloromethane (20 mL) and water (10 mL). The organic layer was separated and the water layer was extracted with dichloromethane (2×20 mL). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The dark residue was purified by silica-gel column chromatography eluting with 30:1 dichloromethane/methanol to afford 291a (104 mg, 60%) as a yellow solid. MS-ESI: [M+H]+ 559.1

출처