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Isophthaloyl chloride → tert-butyl N-[(1S)-2-[[(3S)-5-[(6-bromo-2-methoxy-1-naphthyl)methyl]-1-[3-[(3S)-5-[(6-bromo-2-methoxy-1-naphthyl)methyl]-3-[[(2S)-2-[tert-butoxycarbonyl(methyl)amino]propanoyl]amino]-4-oxo-2,3-dihydro-1,5-benzodiazepine-1-carbonyl]benzoyl]-4-oxo-2,3-dihydro-1,5-benzodiazepin-3-yl]amino]-1-methyl-2-oxo-ethyl]-N-methyl-carbamate

HRID 1481928
ノート
印刷プレビュー

反応式

HRID 1481928 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].[C:41]([O-:44])([O-])=[O:42].[Cs+].[Cs+].[C:47](Cl)(=[O:57])[C:48]1[CH:56]=[CH:55][CH:54]=[C:50]([C:51](Cl)=[O:52])[CH:49]=1>C1COCC1>[Br:32][C:28]1[CH:27]=[C:26]2[C:31](=[CH:30][CH:29]=1)[C:22]([CH2:21][N:18]1[C:17]3[CH:35]=[CH:36][CH:37]=[CH:38][C:16]=3[N:15]([C:47](=[O:57])[C:48]3[CH:56]=[CH:55][CH:54]=[C:50]([C:51]([N:15]4[C:16]5[CH:38]=[CH:37][CH:36]=[CH:35][C:17]=5[N:18]([CH2:21][C:22]5[C:31]6[C:26](=[CH:27][C:28]([Br:32])=[CH:29][CH:30]=6)[CH:25]=[CH:24][C:23]=5[O:33][CH3:34])[C:19](=[O:20])[C@@H:13]([NH:12][C:11](=[O:39])[C@@H:9]([N:7]([C:41]([O:44][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:42])[CH3:6])[CH3:10])[CH2:14]4)=[O:52])[CH:49]=3)[CH2:14][C@H:13]([NH:12][C:11](=[O:39])[C@@H:9]([N:7]([CH3:8])[C:6](=[O:40])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH3:10])[C:19]1=[O:20])=[C:23]([O:33][CH3:34])[CH:24]=[CH:25]2
参加物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 7451Isophthaloyl chlorideHCID 10796Cesium carbonateHCID 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 118677424
tert-butyl N-[(1S)-2-[[(3S)-5-[(6-bromo-2-methoxy-1-naphthyl)methyl]-1-[3-[(3S)-5-[(6-bromo-2-methoxy-1-naphthyl)methyl]-3-[[(2S)-2-[tert-butoxycarbonyl(methyl)amino]propanoyl]amino]-4-oxo-2,3-dihydro-1,5-benzodiazepine-1-carbonyl]benzoyl]-4-oxo-2,3-dihydro-1,5-benzodiazepin-3-yl]amino]-1-methyl-2-oxo-ethyl]-N-methyl-carbamate
収率 5.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a stirred 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) (300 mg, 0.49 mmol) in THF (10.0 mL) was added Cs2CO3 (320 mg, 0.98 mmol) and stirred at RT for 3 h. The mixture was cooled to 0° C., isophthaloyl dichloride (49 mg, 0.24 mmol) was added, the cooling bath was removed and the mixture was stirred at RT. After 18 h, the mixture was diluted with ethyl acetate, washed with water and brine. The organic layer was evaporated and the residue purified by preparative reverse phase HPLC to afford tert-butyl N-[(1S)-2-[[(3S)-5-[(6-bromo-2-methoxy-1-naphthyl)methyl]-1-[3-[(3S)-5-[(6-bromo-2-methoxy-1-naphthyl)methyl]-3-[[(2S)-2-[tert-butoxycarbonyl(methyl)amino]propanoyl]amino]-4-oxo-2,3-dihydro-1,5-benzodiazepine-1-carbonyl]benzoyl]-4-oxo-2,3-dihydro-1,5-benzodiazepin-3-yl]amino]-1-methyl-2-oxo-ethyl]-N-methyl-carbamate (18 mg, 3%). LC-MS: 1353.8 (M+H), 1370.8 (M+NH4).

後処理

  1. temperatureThe mixture was cooled to 0° C.
  2. customthe cooling bath was removed
  3. stirringthe mixture was stirred at RT
  4. waitAfter 18 h
  5. additionthe mixture was diluted with ethyl acetate
  6. washwashed with water and brine
  7. customThe organic layer was evaporated
  8. customthe residue purified by preparative reverse phase HPLC

出典と根拠

ORDレコード
ord-25407adc31cb4a498b8c363f701117a6
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

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート