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Lithium hydroxide, monohydrate → 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

HRID 1481909
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HRID 1481909 반응식
C[O:2][C:3](=[O:52])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([N:12]2[CH2:18][C@H:17]([NH:19][C:20](=[O:32])[C@@H:21]([N:23]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH3:24])[CH3:22])[C:16](=[O:33])[N:15]([CH2:34][C:35]3[C:44]4[C:39](=[CH:40][C:41]([Br:45])=[CH:42][CH:43]=4)[CH:38]=[CH:37][C:36]=3[O:46][CH3:47])[C:14]3[CH:48]=[CH:49][CH:50]=[CH:51][C:13]2=3)=[O:11])=[CH:6][CH:5]=1.O[Li].O>C1COCC1.CO.O.O>[Br:45][C:41]1[CH:40]=[C:39]2[C:44](=[CH:43][CH:42]=1)[C:35]([CH2:34][N:15]1[C:16](=[O:33])[C@@H:17]([NH:19][C:20](=[O:32])[C@@H:21]([N:23]([C:25]([O:27][C:28]([CH3:30])([CH3:31])[CH3:29])=[O:26])[CH3:24])[CH3:22])[CH2:18][N:12]([C:10]([C:7]3[CH:8]=[CH:9][C:4]([C:3]([OH:52])=[O:2])=[CH:5][CH:6]=3)=[O:11])[C:13]3[CH:51]=[CH:50][CH:49]=[CH:48][C:14]1=3)=[C:36]([O:46][CH3:47])[CH:37]=[CH:38]2
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참가 물질

5

반응물 2

HCID 168937Lithium hydroxide, monohydrateHCID 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 ester2회

생성물 1

HCID 902209134-{(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 acid수율 91.6%

시약·촉매·용매 2

HCID 962Water용매HCID 21892291Methanol tetrahydrofuran water용매

실험 절차

To a solution of 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 (Intermediate 19) (4 g, 5.175 mmol) in THF-MeOH-water 1:1:1 (90 mL) were slowly added a solution of LiOH.H2O solution (574 mg, 13.6 m mol) in water. After 4 h the mixture was concentrated, the residue was diluted with water and acidified to pH˜3 with 1 N HCl. The mixture was extracted with ethyl acetate, the extracts were dried over sodium sulfate and evaporated. The residue was triturated with hexane to give the title compound (3.6 g, 91.58%) as an off white solid. LC-MS: 759 (M+H).

후처리

  1. concentrationAfter 4 h the mixture was concentrated
  2. additionthe residue was diluted with water
  3. extractionThe mixture was extracted with ethyl acetate
  4. dry with materialthe extracts were dried over sodium sulfate
  5. customevaporated
  6. customThe residue was triturated with hexane

출처 및 근거

ORD 기록
ord-5501cc82b23e4b0db6bbdfa3b7077300
출처 데이터셋
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09409888B2

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