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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
ノート
印刷プレビュー

反応式

HRID 1481908 の反応式
[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
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

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 ester2 回

生成物 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

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒

反応条件

温度
0 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-f213559c13cb4377a8fa2521874313d9
出典データセット
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09409888B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート