Hydrochloric Acid → 8-Fluoro-3-methyl-1-oxo-2-propyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-amide

HRID 884758

Reaktionsgleichung

Reaktionsgleichung von HRID 884758
C(Cl)(=O)C(Cl)=O.[CH2:7]([NH:10][C:11](=O)[CH3:12])[CH2:8][CH3:9].N1C(C)=CC=CC=1C.[CH:22]1([C@H:25]([NH:33][C:34]([CH2:36][C:37]2[CH:45]=[CH:44][CH:43]=[C:42]([F:46])[C:38]=2[C:39]([OH:41])=O)=[O:35])[C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=2)[CH2:24][CH2:23]1.Cl>ClCCCl.[Cl-].[Na+].O>[CH:22]1([C@H:25]([NH:33][C:34]([C:36]2[C:37]3[C:38](=[C:42]([F:46])[CH:43]=[CH:44][CH:45]=3)[C:39](=[O:41])[N:10]([CH2:7][CH2:8][CH3:9])[C:11]=2[CH3:12])=[O:35])[C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=2)[CH2:23][CH2:24]1

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 79372,6-LutidineHCID 21407N-PropylacetamideHCID 65578Oxalyl chlorideHCID 577334122-({[(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-carbamoyl}-methyl)-6-fluoro-benzoic acid

Produkt 1

HCID 592530488-Fluoro-3-methyl-1-oxo-2-propyl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-amideAusbeute 42 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Oxalyl chloride (0.7 mL, 8 mmol) was added to N-propyl-acetamide (1.11 mL, 10 mmol) and 2,6-lutidine (1.39 mL, 12 mmol) in 50 mL 1,2-dichloroethane at 0° C. The reaction mixture was stirred at 0° C. for 30 minutes. 2-({[(S)-Cyclopropyl-(3-fluoro-phenyl)-methyl]-carbamoyl}-methyl)-6-fluoro-benzoic acid was added and the reaction mixture was refluxed for 20 hours. The reaction mixture was poured into 35 mL 1N HCl (aq.) and 50 mL brine. The mixture was extracted with ethyl acetate (250 mL). The organic phase was washed with brine, dried over MgSO4 and concentrated in vacuo. The crude product was flash chromatographed on silica gel (gradient heptane-ethyl acetate) to give 344 mg of the title compound, yield 42%. LC-MS (m/z) 411.3 (MH+); tR=1.34.

Aufarbeitung

  1. temperaturethe reaction mixture was refluxed for 20 hours
  2. extractionThe mixture was extracted with ethyl acetate (250 mL)
  3. washThe organic phase was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customchromatographed on silica gel (gradient heptane-ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-6ff10ff9ecf247629dcda26e4152d58e
Quelldatensatz
uspto-grants-2012_08
Patentnummer
US08242134B2

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