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Sodium hydride → 1,1-Dimethylethyl 6-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate

HRID 1514187
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HRID 1514187 반응식
[OH:1][NH:2][C:3](=[NH:22])[C:4]1[C:14]2[CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10][CH2:9][C:8]=2[CH:7]=[CH:6][CH:5]=1.[H-].[Na+].[Cl:25][C:26]1[CH:27]=[C:28]([CH:33]=[CH:34][C:35]=1[O:36][CH:37]([CH3:39])[CH3:38])[C:29](OC)=O>C1COCC1>[Cl:25][C:26]1[CH:27]=[C:28]([C:29]2[O:1][N:2]=[C:3]([C:4]3[C:14]4[CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[CH2:10][CH2:9][C:8]=4[CH:7]=[CH:6][CH:5]=3)[N:22]=2)[CH:33]=[CH:34][C:35]=1[O:36][CH:37]([CH3:38])[CH3:39]
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참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 22597811Methyl 3-chloro-4-isopropoxybenzoateHCID 178451587HCID 178451587, 화합물

생성물 1

HCID 594034711,1-Dimethylethyl 6-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

1,1-dimethylethyl 6-[(hydroxyamino)(imino)methyl]-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate (Preparation 15) (170 mg, 0.557 mmol) was dissolved in THF (30 ml) and stirred with sodium hydride (24.49 mg, 0.612 mmol) under argon at room temperature for 30 minutes. Then methyl 3-chloro-4-[(1-methylethyl)oxy]benzoate (may be prepared as described in WO2005058848) (191 mg, 0.835 mmol) was added and the reaction heated at reflux temperature for 1.5 hours. The cooled reaction was evaporated and partitioned between DCM (100 ml) and water (100 ml). The water layer was washed with DCM (50 ml) and the combined DCM layers dried (hydrophobic frit) and evaporated. The title compound was isolated by silica chromatography (eluting with DCM). 1,1-dimethylethyl 6-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate (260 mg, 0.537 mmol, 96% yield) was isolated as an off-white foam. δH (400 MHz, CDCl3) 8.22 (1H, s), 8.05 (1H d), 7.68 (1H, d), 7.30-7.24 (2H, m), 7.06 (1H, d), 4.72 (1H, sept), 3.65-3.55 (4H, m), 3.35-3.25 (2H, m), 2.95-3.05 (2H, m); 1.45 (6H, d), 1.43 (9H, s); MS (ES) C26H3035ClN3O4 requires 483; found 484 [M+H]+.

후처리

  1. temperaturethe reaction heated
  2. temperatureat reflux temperature for 1.5 hours
  3. customThe cooled reaction
  4. customwas evaporated
  5. custompartitioned between DCM (100 ml) and water (100 ml)
  6. washThe water layer was washed with DCM (50 ml)
  7. dry with materialthe combined DCM layers dried (hydrophobic frit)
  8. customevaporated

출처 및 근거

ORD 기록
ord-3301ed6ade5b43e08bde70f702ece6e4
출처 데이터셋
uspto-grants-2012_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08222245B2

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