Hydrochloric Acid → Methyl (S)-1-((S)-2-(6-(7-bromo-9,10-dihydrophenanthren-2-yl)-1H-benzo[d]imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate

HRID 1751579노트

반응식

HRID 1751579 반응식
[Br:1][C:2]1[CH:15]=[C:14]2[C:5]([C:6]3[CH:7]=[CH:8][C:9]([C:16]4[CH:17]=[CH:18][C:19]5[N:23]=[C:22]([C@@H:24]6[CH2:28][CH2:27][CH2:26][N:25]6C(OC(C)(C)C)=O)[NH:21][C:20]=5[CH:36]=4)=[CH:10][C:11]=3[CH2:12][CH2:13]2)=[CH:4][CH:3]=1.Cl.[CH3:38][O:39][C:40]([NH:42][C@@H:43]([CH:47]([CH3:49])[CH3:48])[C:44](O)=[O:45])=[O:41].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CO.C(OCC)(=O)C>[Br:1][C:2]1[CH:15]=[C:14]2[C:5]([C:6]3[CH:7]=[CH:8][C:9]([C:16]4[CH:17]=[CH:18][C:19]5[N:23]=[C:22]([C@@H:24]6[CH2:28][CH2:27][CH2:26][N:25]6[C:44](=[O:45])[C@@H:43]([NH:42][C:40](=[O:41])[O:39][CH3:38])[CH:47]([CH3:49])[CH3:48])[NH:21][C:20]=5[CH:36]=4)=[CH:10][C:11]=3[CH2:12][CH2:13]2)=[CH:4][CH:3]=1

참가 물질

8

반응물 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 67681965(S)-tert-butyl 2-(6-(7-bromo-9,10-dihydro-phenanthren-2-yl)-1H-benzo[d]imidazol-2-yl)-pyrrolidine-1-carboxylate

생성물 1

HCID 67681948Methyl (S)-1-((S)-2-(6-(7-bromo-9,10-dihydrophenanthren-2-yl)-1H-benzo[d]imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate수율 58%

시약·촉매·용매 2

HCID 887Methanol용매HCID 8857Ethyl Acetate용매

실험 절차

A solution of (S)-tert-butyl 2-(6-(7-bromo-9,10-dihydro-phenanthren-2-yl)-1H-benzo[d]imidazol-2-yl)-pyrrolidine-1-carboxylate (582 mg, 1.1 mmol), 4M HCl solution in dioxanes (5 mL, 20 mmol) and methanol (3 mL) was stirred at room temperature for twenty minutes. The reaction was concentrated, suspended in dichloromethane, and thoroughly concentrated. This crude amine was dissolved in dimethylformamide (5 mL). To this solution were added (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (281 mg, 1.6 mmol), HATU (691 mg, 1.8 mmol) and diisopropylethylamine (0.65 mL, 3.7 mmol). The reaction was stirred at room temperature for fifteen minutes, and then diluted ethyl acetate. The organic layer was washed with saturated aqueous NaHCO3 solution and brine, dried (Na2SO4) and concentrated. The crude material was purified by flash column chromatography to yield Methyl (S)-1-((S)-2-(6-(7-bromo-9,10-dihydrophenanthren-2-yl)-1H-benzo[d]imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (376 mg, 58%).

후처리

  1. concentrationThe reaction was concentrated
  2. concentrationthoroughly concentrated
  3. dissolutionThis crude amine was dissolved in dimethylformamide (5 mL)
  4. washThe organic layer was washed with saturated aqueous NaHCO3 solution and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude material was purified by flash column chromatography

출처 및 근거

ORD 기록
ord-a56cdc528dfa48929dc44c14c41a859c
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09156823B2

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