Hydrochloric Acid → {1-[2-(4'-Bromo-biphenyl-4-ylcarbamoyl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester

HRID 2039099Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2039099
C(OC([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13](=[O:28])[NH:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][C:24]([Br:27])=[CH:23][CH:22]=2)=[CH:17][CH:16]=1)=O)(C)(C)C.Cl.[CH3:30][O:31][C:32]([NH:34][CH:35]([CH:39]([CH3:41])[CH3:40])[C:36](O)=[O:37])=[O:33].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CO.C(OCC)(=O)C.CN(C=O)C>[CH3:30][O:31][C:32](=[O:33])[NH:34][CH:35]([C:36]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13](=[O:28])[NH:14][C:15]1[CH:16]=[CH:17][C:18]([C:21]2[CH:26]=[CH:25][C:24]([Br:27])=[CH:23][CH:22]=2)=[CH:19][CH:20]=1)=[O:37])[CH:39]([CH3:41])[CH3:40]

Komponenten

9

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 138211012-((Methoxycarbonyl)amino)-3-methylbutanoic acidHCID 666213242-(4'-Bromo-biphenyl-4-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 66620562{1-[2-(4'-Bromo-biphenyl-4-ylcarbamoyl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl esterAusbeute 93,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

2-(4′-Bromo-biphenyl-4-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (496 mg, 1.11 mmol) was dissolved in methanol and concentrated HCl (2 mL) was added. The solution was stirred at 60° C. for 30 min then concentrated. The resulting residue was treated with 2-methoxycarbonylamino-3-methyl-butyric acid (233 mg, 1.33 mmol), HATU (549 mg, 1.44 mmol) and DMF (10 mL) After cooling this mixture to 0° C., DIPEA (0.970 mL, 5.55 mmol) was added. The reaction mixture was Stirred for 5 hours then diluted with ethyl acetate (150 mL) and washed with water and brine. The organic phase was dried over magnesium sulfate and concentrated. The resulting residue was purified by silica column chromatography (70% to 90% EtOAc/hexanes) to afford {1-[2-(4′-Bromo-biphenyl-4-ylcarbamoyl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (520 mg, 93% over 2 steps).

Aufarbeitung

  1. concentrationthen concentrated
  2. temperatureAfter cooling this mixture to 0° C.
  3. stirringThe reaction mixture was Stirred for 5 hours
  4. washwashed with water and brine
  5. dry with materialThe organic phase was dried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe resulting residue was purified by silica column chromatography (70% to 90% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-bcb69e896cd94524bebd7e12322bde3c
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08575118B2

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