Phenylacetylene → 1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-[4-(5-phenyl-3-isoxazolyl)-2-thiazolyl]piperidine

HRID 238654노트

반응식

HRID 238654 반응식
[OH:1][N:2]=[CH:3][C:4]1[N:5]=[C:6]([CH:9]2[CH2:14][CH2:13][N:12]([C:15](=[O:27])[CH2:16][N:17]3[C:21]([CH3:22])=[CH:20][C:19]([C:23]([F:26])([F:25])[F:24])=[N:18]3)[CH2:11][CH2:10]2)[S:7][CH:8]=1.[C:28]1([C:34]#[CH:35])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.Cl[O-].[Na+]>O1CCCC1>[CH3:22][C:21]1[N:17]([CH2:16][C:15]([N:12]2[CH2:13][CH2:14][CH:9]([C:6]3[S:7][CH:8]=[C:4]([C:3]4[CH:35]=[C:34]([C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=5)[O:1][N:2]=4)[N:5]=3)[CH2:10][CH2:11]2)=[O:27])[N:18]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:20]=1

참가 물질

5

반응물 3

HCID 10821PhenylacetyleneHCID 23665760Sodium HypochloriteHCID 866312434-[4-[(hydroxyimino)methyl]-2-thiazolyl]-1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]piperidine2회

생성물 1

HCID 687422261-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-[4-(5-phenyl-3-isoxazolyl)-2-thiazolyl]piperidine

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

4-[4-[(Hydroxyimino)methyl]-2-thiazolyl]-1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]piperidine (i.e. the product of Example 2, Step C) (0.2 g, 0.5 mmol) was suspended in tetrahydrofuran (20 mL), and phenylacetylene (1.1 mL, 1 mmol) was added, followed by a slow dropwise addition of Clorox® bleach solution (6.15 wt. % sodium hypochlorite, 10 mL) over 1 h. The reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3×30 mL). The combined organic layers were washed with brine, dried (MgSO4) and concentrated under reduced pressure to give an oil, which was purified by flash column chromatography on silica gel using 10% methanol in ethyl acetate as eluant to give 70 mg of the title product, a compound of present invention, as a clear yellow oil.

후처리

  1. customThe reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with ethyl acetate (3×30 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. customto give an oil, which
  8. customwas purified by flash column chromatography on silica gel using 10% methanol in ethyl acetate as eluant

출처 및 근거

ORD 기록
ord-40683a75493043cf9166a2b746ac6750
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08642634B2

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