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 1751579Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1751579
[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

Komponenten

8

Edukt 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

Produkt 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-ylcarbamateAusbeute 58 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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%).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-a56cdc528dfa48929dc44c14c41a859c
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09156823B2

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