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Monomethyl terephthalate → 4-{(S)-5-(6-Bromo-2-methoxy-naphthalen-1-ylmethyl)-3-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-4-oxo-2,3,4,5-tetrahydro-benzo[b][1,4]diazepine-1-carbonyl}-benzoic acid methyl ester

HRID 1481908
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인쇄 미리보기

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HRID 1481908 반응식
[C:1]([O:5][C:6](=[O:40])[N:7]([C@H:9]([C:11](=[O:39])[NH:12][C@@H:13]1[C:19](=[O:20])[N:18]([CH2:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([Br:32])=[CH:29][CH:30]=3)[CH:25]=[CH:24][C:23]=2[O:33][CH3:34])[C:17]2[CH:35]=[CH:36][CH:37]=[CH:38][C:16]=2[NH:15][CH2:14]1)[CH3:10])[CH3:8])([CH3:4])([CH3:3])[CH3:2].[CH3:41][O:42][C:43](=[O:53])[C:44]1[CH:52]=[CH:51][C:47]([C:48](O)=[O:49])=[CH:46][CH:45]=1.O=P(Cl)(Cl)Cl>N1C=CC=CC=1>[CH3:41][O:42][C:43](=[O:53])[C:44]1[CH:52]=[CH:51][C:47]([C:48]([N:15]2[CH2:14][C@H:13]([NH:12][C:11](=[O:39])[C@@H:9]([N:7]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:40])[CH3:8])[CH3:10])[C:19](=[O:20])[N:18]([CH2:21][C:22]3[C:31]4[C:26](=[CH:27][C:28]([Br:32])=[CH:29][CH:30]=4)[CH:25]=[CH:24][C:23]=3[O:33][CH3:34])[C:17]3[CH:35]=[CH:36][CH:37]=[CH:38][C:16]2=3)=[O:49])=[CH:46][CH:45]=1
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5

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HCID 15513Monomethyl terephthalateHCID 24813Phosphorus oxychlorideHCID 72713837{(S)-1-[(S)-1-(6-Bromo-2-methoxy-naphthalen-1-ylmethyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester2회

생성물 1

HCID 902212384-{(S)-5-(6-Bromo-2-methoxy-naphthalen-1-ylmethyl)-3-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-4-oxo-2,3,4,5-tetrahydro-benzo[b][1,4]diazepine-1-carbonyl}-benzoic acid methyl ester

시약·촉매·용매 1

HCID 1049Pyridine용매

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온도
0 °C

실험 절차

To a solution of {(S)-1-[(S)-1-(6-bromo-2-methoxy-naphthalen-1-ylmethyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester (Intermediate 11) (1.5 g, 2.455 mmol) in pyridine (20 mL) at 0° C. was added terephthalic acid monomethyl ester (884 mg, 4.91 mmol). The mixture was stirred for 10 min at 0° C. and POCl3 (0.472 mL, 5.155 mmol) was slowly added, the cooling bath removed and the mixture stirred at RT. After 16 h the mixture was evaporated and the residue diluted with ice water and extracted with ethyl acetate. The combined extracts were washed with water, brine, dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography to give the title compound. The sequence was repeated to provide a total of 4.2 g of the title compound from as an off white solid. LC-MS: 773 (M+H).

후처리

  1. customthe cooling bath removed
  2. stirringthe mixture stirred at RT
  3. customAfter 16 h the mixture was evaporated
  4. additionthe residue diluted with ice water
  5. extractionextracted with ethyl acetate
  6. washThe combined extracts were washed with water, brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-f213559c13cb4377a8fa2521874313d9
출처 데이터셋
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09409888B2

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