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

반응식

HRID 884758 반응식
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

참가 물질

8

반응물 5

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

생성물 1

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

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 57417360Sodium chloride; water용매

반응 조건

온도
0 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-6ff10ff9ecf247629dcda26e4152d58e
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08242134B2

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