Hydrochloric Acid → (1-{2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-4-difluoromethoxymethyl-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

HRID 1185898Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1185898
C(OC([N:8]1[CH2:12][CH:11]([CH2:13][O:14][CH:15]([F:17])[F:16])[CH2:10][CH:9]1[C:18]1[NH:19][C:20]([C:23]2[CH:28]=[CH:27][C:26]([Br:29])=[CH:25][CH:24]=2)=[CH:21][N:22]=1)=O)(C)(C)C.Cl.[CH3:31][O:32][C:33]([NH:35][CH:36]([CH:40]([CH3:42])[CH3:41])[C:37](O)=[O:38])=[O:34].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C.CCOC(C)=O>[CH3:31][O:32][C:33](=[O:34])[NH:35][CH:36]([C:37]([N:8]1[CH2:12][CH:11]([CH2:13][O:14][CH:15]([F:17])[F:16])[CH2:10][CH:9]1[C:18]1[NH:19][C:20]([C:23]2[CH:28]=[CH:27][C:26]([Br:29])=[CH:25][CH:24]=2)=[CH:21][N:22]=1)=[O:38])[CH:40]([CH3:42])[CH3:41]

Komponenten

9

Edukt 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 138211012-((Methoxycarbonyl)amino)-3-methylbutanoic acidHCID 666207862-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-4-difluoromethoxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 66620824(1-{2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-4-difluoromethoxymethyl-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl esterAusbeute 61 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-4-difluoromethoxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester was dissolved in DCM (4 mL) and treated with HCl (4.0M in dioxane, 1 mL, 4 mmol). After 2.5 h, the solution was concentrated and the residue was treated with 2-Methoxycarbonylamino-3-methyl-butyric acid (55 mg, 0.315 mmol) and HATU (120 mg, 0.315 mmol). The solids were suspended in DMF (3 mL) and the reaction mixture was cooled to 0° C. before triethylamine (0.25 mL, 1.43 mmol) was added in a dropwise fashion. After 30 min, the mixture was warmed to RT. After another 1 h, it was diluted with EtOAc and washed with saturated aqueous NaHCO3 and brine. Then it was dried over MgSO4, filtered and concentrated. The crude residue was purified by silica column chromatography (60% to 100% EtOAc/Hex) to afford the title compound (92 mg, 61%).

Aufarbeitung

  1. concentrationthe solution was concentrated
  2. additionwas added in a dropwise fashion
  3. waitAfter 30 min
  4. waitAfter another 1 h
  5. washwashed with saturated aqueous NaHCO3 and brine
  6. dry with materialThen it was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue was purified by silica column chromatography (60% to 100% EtOAc/Hex)

Quellen und Nachweise

ORD-Eintrag
ord-852a42c63e02476797a690e8e7e75d14
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08669234B2

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