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对苯二甲酸单甲酯 → 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
笔记
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反应方程式

HRID 1481908 反应方程式
[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
参与物反应条件实验过程后处理来源与证据反应笔记

参与物

5

反应物 3

HCID 15513对苯二甲酸单甲酯HCID 24813三氯氧磷HCID 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 ester2 次

产物 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

试剂、催化剂与溶剂 1

HCID 1049吡啶溶剂

反应条件

温度
0 °C

实验过程

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).

后处理

  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

来源与证据

ORD记录
ord-f213559c13cb4377a8fa2521874313d9
来源数据集
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
专利号
US09409888B2

反应笔记

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本页导航参与物反应条件实验过程后处理来源与证据反应笔记