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Water → Ethyl 3-(benzyloxy)-10-(((benzyloxy)carbonyl)amino)-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylate

HRID 80687
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HRID 80687 반응식
[CH2:1]([O:8][C:9]([NH:11][C:12]12[CH2:20][CH2:19][CH:16]([CH2:17][CH2:18]1)[CH2:15][N:14]1[C:21](=[O:31])[C:22]([OH:30])=[C:23]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:24]=[C:13]21)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH2:38](Br)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.O>CN(C=O)C>[CH2:38]([O:30][C:22]1[C:21](=[O:31])[N:14]2[CH2:15][CH:16]3[CH2:17][CH2:18][C:12]([NH:11][C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[O:10])([C:13]2=[N:24][C:23]=1[C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:20][CH2:19]3)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1
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6

반응물 4

HCID 962WaterHCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 57904801Ethyl 10-(((benzyloxy)carbonyl)amino)-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylate

생성물 1

HCID 67960300Ethyl 3-(benzyloxy)-10-(((benzyloxy)carbonyl)amino)-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylate
수율 42%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
50 °C

실험 절차

To a solution of ethyl 10-(((benzyloxy)carbonyl)amino)-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylate (prepared according to the procedure in WO2009117540) (500 mg, 1.170 mmol) in DMF (20 mL) was added K2CO3 (323 mg, 2.339 mmol) followed by benzyl bromide (0.208 mL, 1.755 mmol) and the resulting mixture was heated at 50° C. for 16 h. After cooling to room temp, water was added and the mixture was extracted with ethyl acetate, dried (Na2SO4), filtered and concentrated. The crude product was purified by silica gel chromatography (20-100% ethyl acetate/hexane to afford the title compound (250 mg, 42% yield) as a light yellow liquid. 1H NMR (500 MHz, CDCl3) δ: 7.47 (d, 2H, J=7.02 Hz), 7.32-7.39 (m, 8H), 7.19 (brs, 1H), 5.26 (s, 2H), 5.08 (s, 2H), 4.31 (q, 2H, J=7.02 Hz), 4.13 (d, 2H, J=3.97 Hz), 2.87-2.96 (m, 2H), 2.46 (brs, 1H), 1.94-2.03 (m, 2H), 1.80-1.89 (m, 2H), 1.65-1.75 (m, 2H), 1.29 (t, 3H, J=7.32 Hz). LCMS (M+H)=518.28.

후처리

  1. temperatureAfter cooling to room temp
  2. extractionthe mixture was extracted with ethyl acetate
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by silica gel chromatography (20-100% ethyl acetate/hexane

출처 및 근거

ORD 기록
ord-ff8971ee92014fd7976cf73e49379833
출처 데이터셋
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08846659B2

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