반응 #162913

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TFA

methylpyridine

trimethyloxonium tetrafluoroborate

N-[2-[[[(4-fluoro-3-methylphenyl)methyl]amino]carbonyl]-6,7,8,9-tetrahydro-3-hydroxy-7-[[[(4-methylphenyl)sulfonyl]oxy]methyl]-4-oxo-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl]-N,N′,N′-trimethyl-ethanediamide

2,6-di-tert-butyl-4-methylpyridine

trimethyloxonium tetrafluoroborate

→

title compound

수율 3.8%

N-[2-[[[(4-Fluoro-3-methylphenyl)methyl]amino]carbonyl]-6,7,8,9-tetrahydro-3-hydroxy-7-(methoxymethyl)-4-oxo-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl]-N,N′,N′-trimethyl-ethanediamide

수율 3.8%

용매

CH2Cl2

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후처리

1. 1
   workup.STIRRINGthe mixture was stirred at room temp for 5 h
2. 2
   기타The reaction was quenched by addition of 1N KHSO4 (30 mL)
3. 3
   workup.STIRRINGstirred for 10 min
4. 4
   추출extracted with CH2Cl2 (25 mL×2)
5. 5
   기타The combined extracts were dried
6. 6
   여과filtered
7. 7
   농축concentrated
8. 8
   workup.DISSOLUTIONThe crude material was then dissolved in CH2Cl2 (1 mL)
9. 9
   농축The mixture was concentrated in vacuuo
10. 10
    기타purified by preparative HPLC

실험 절차

To a solution of N-[2-[[[(4-fluoro-3-methylphenyl)methyl]amino]carbonyl]-6,7,8,9-tetrahydro-3-hydroxy-7-[[[(4-methylphenyl)sulfonyl]oxy]methyl]-4-oxo-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl]-N,N′,N′-trimethyl-ethanediamide, Intermediate 28, (100 mg, 0.161 mmol) in CH2Cl2 (10 mL) was added 2,6-di-tert-butyl-4-methylpyridine (166 mg, 0.807 mmol) and trimethyloxonium tetrafluoroborate (48.5 mg, 0.807 mmol) and the mixture was stirred at room temp for 16 h. Another 5 equiv each of methylpyridine and trimethyloxonium tetrafluoroborate were added and the mixture was stirred at room temp for 5 h. The reaction was quenched by addition of 1N KHSO4 (30 mL) and stirred for 10 min and extracted with CH2Cl2 (25 mL×2). The combined extracts were dried, filtered and concentrated. The crude material was then dissolved in CH2Cl2 (1 mL) and treated with TFA (1 mL, 12.98 mmol) at room temp for 16 h. The mixture was concentrated in vacuuo and purified by preparative HPLC to afford the title compound (3.5 mg, 6.12 mmol, 3.79% yield) as a thick film. 1H NMR (500 MHz, CDCl3) δ: 12.15 (1H, br. s.), 9.59 (1H, br. s.), 7.24-7.27 (1H, m), 7.17-7.23 (1H, m), 6.90-6.97 (1H, m), 4.71 (1H, d, J=15.6 Hz), 4.58-4.65 (1H, m), 4.43-4.48 (1H, m), 3.51 (1H, d, J=15.6 Hz), 3.39-3.45 (1H, m), 3.20 (2H, d, J=5.8 Hz), 3.05 (3H, s), 3.02 (3H, s), 3.00 (3H, s), 2.27 (3H, d, J=1.8 Hz), 2.08-2.12 (3H, m), 1.76-1.83 (1H, m), 1.66-1.74 (2H, m), 1.38-1.49 (1H, m). LCMS (M+H)=544.5.

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