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Sodium Bicarbonate → Ammonia

HRID 2383366
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HRID 2383366 반응식
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][CH:14]([CH2:17][N:18]2[CH:22]=[N:21][C:20]([C@@:23]([CH:31]3[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]3)([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[OH:24])=[N:19]2)[CH2:13][CH2:12]1.[CH2:37]([O:44][C:45]1[CH:46]=[CH:47][C:48]([C@@H:56]([O:59][Si:60]([C:63]([CH3:66])([CH3:65])[CH3:64])([CH3:62])[CH3:61])[CH2:57]Br)=[C:49]2[C:54]=1[NH:53][C:52](=[O:55])[CH:51]=[CH:50]2)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C(=O)([O-])O.[Na+]>C(#N)C>[NH3:1].[CH2:37]([O:44][C:45]1[CH:46]=[CH:47][C:48]([C@@H:56]([O:59][Si:60]([C:63]([CH3:64])([CH3:66])[CH3:65])([CH3:62])[CH3:61])[CH2:57][NH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][N:11]2[CH2:12][CH2:13][CH:14]([CH2:17][N:18]3[CH:22]=[N:21][C:20]([C@:23]([CH:31]4[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]4)([OH:24])[C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[N:19]3)[CH2:15][CH2:16]2)=[C:49]2[C:54]=1[NH:53][C:52](=[O:55])[CH:51]=[CH:50]2)[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1
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참가 물질

6

반응물 3

HCID 516892Sodium BicarbonateHCID 15606253(R)-8-(benzyloxy)-5-(2-bromo-1-((tert-butyldimethylsilyl)oxy)ethyl)quinolin-2(1H)-oneHCID 59145972(R)-(1-{[1-(9-aminononyl)piperidin-4-yl]methyl}-1H-1,2,4-triazol-3-yl)(cyclohexyl) phenylmethanol

생성물 2

HCID 222Ammonia
HCID 59145949
8-(benzyloxy)-5-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-({9-[4-({3-[(R)-cyclohexyl(hydroxy)phenylmethyl]-1H-1,2,4-triazol-1-yl}methyl)piperidin-1-yl]nonyl}amino)ethyl]quinolin-2(1H)-one

시약·촉매·용매 1

HCID 6342Acetonitrile용매

반응 조건

온도
90 °C

실험 절차

(R)-(1-{[1-(9-aminononyl)piperidin-4-yl]methyl}-1H-1,2,4-triazol-3-yl)(cyclohexyl) phenylmethanol (Preparation 6, 350 mg, 0.706 mg), 8-(benzyloxy)-5-[(1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl]quinolin-2(1H)-one (WO200509286, 345 mg, 0.706 mmol) and sodium hydrogen carbonate (88.9 mg, 1.06 mmol) were combined in acetonitrile (7 mL). After stirring at 90° C. for 72 hours the solvent was removed in vacuo and residue partitioned between dichloromethane (50 ml) and saturated aqueous sodium bicarbonate solution (50 mL). The organic layer was separated, dried over magnesium sulphate, filtered and the solvent removed in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (99:1:0.1 to 95:5:0.5 by volume) to furnish the title compound as a clear glass, in 37% yield, 240 mg (contains 10% of other triazole regio-isomer).

후처리

  1. customwas removed in vacuo and residue
  2. custompartitioned between dichloromethane (50 ml) and saturated aqueous sodium bicarbonate solution (50 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. customthe solvent removed in vacuo
  7. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane

출처 및 근거

ORD 기록
ord-47ab3ab4541f4591bc7e4a193aee6931
출처 데이터셋
uspto-grants-2012_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08263623B2

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