HCID 86711207, 화합물 → HCID 86711208, 화합물

HRID 1850790노트

반응식

HRID 1850790 반응식
[F:1][C:2]1[CH:21]=[C:20]([S:22]([CH3:25])(=[O:24])=[O:23])[CH:19]=[CH:18][C:3]=1[O:4][CH2:5][CH2:6][C@@H:7]1[CH2:9][C@@H:8]1[CH:10]1[CH2:15][CH2:14][N:13]([C:16]#[N:17])[CH2:12][CH2:11]1.[OH:26][NH:27][C:28](=N)[CH2:29][O:30][CH3:31]>O1CCCC1.[Cl-].[Zn+2].[Cl-]>[F:1][C:2]1[CH:21]=[C:20]([S:22]([CH3:25])(=[O:23])=[O:24])[CH:19]=[CH:18][C:3]=1[O:4][CH2:5][CH2:6][C@H:7]1[CH2:9][C@H:8]1[CH:10]1[CH2:11][CH2:12][N:13]([C:16]2[O:26][N:27]=[C:28]([CH2:29][O:30][CH3:31])[N:17]=2)[CH2:14][CH2:15]1

참가 물질

5

반응물 2

HCID 86711207HCID 86711207, 화합물HCID 178496050HCID 178496050, 화합물

생성물 1

HCID 86711208HCID 86711208, 화합물

시약·촉매·용매 2

HCID 3007855Zincchloride촉매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 4-((1R,2S)-2-{2-{2-fluoro-4-(methylsulfonyl)phenoxy]ethyl}cyclopropyl)piperidine-1-carbonitrile (Step D, Example 111; 100 mg, 0.27 mmol) and N-hydroxy-2-methoxyacetimidamide (38 mg, 0.37 mmol) in tetrahydrofuran (5 mL) was added zinc chloride (0.8 mL, 0.5 M in tetrahydrofuran, 0.4 mmol). The mixture was refluxed for 2 h, cooled to RT, and concentrated to dryness under reduced pressure. The residue was dissolved in 2 mL of 4N HCl ethanol and water (1:1). The solution was refluxed for 30 min, cooled to RT, and concentrated to dryness under reduced pressure. The residue was dissolved in methanol (5 mL), neutralized by the addition of excess potassium carbonate, mixed silica gel (2 g), and concentrated to dryness under reduced pressure. The residue was loaded on a silica gel column (10 g of silica gel) and eluted with a gradient of dichloromethane/CMA, 19:1, 500 mL; 4:1, 500 mL to provide the title compound. MS (ESI) m/z 454 [M+H]+.

후처리

  1. temperatureThe mixture was refluxed for 2 h
  2. concentrationconcentrated to dryness under reduced pressure
  3. dissolutionThe residue was dissolved in 2 mL of 4N HCl ethanol
  4. temperatureThe solution was refluxed for 30 min
  5. temperaturecooled to RT
  6. concentrationconcentrated to dryness under reduced pressure
  7. dissolutionThe residue was dissolved in methanol (5 mL)
  8. additionneutralized by the addition of excess potassium carbonate
  9. additionmixed silica gel (2 g)
  10. concentrationconcentrated to dryness under reduced pressure
  11. washeluted with a gradient of dichloromethane/CMA, 19:1, 500 mL

출처 및 근거

ORD 기록
ord-4ca24d07ce524cad8ca603b7e6b8a939
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08957062B2

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