Water → 1-[4-(4-{5-[2-(allyloxy)phenyl]-4,5-dihydro-1,2-oxazol-3-yl}-1,3-thiazol-2-yl)piperidin-1-yl]-2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethanone

HRID 1753740Notes

Reaction equation

HRID 1753740 reaction equation
[F:1][CH:2]([F:37])[C:3]1[CH:7]=[C:6]([CH:8]([F:10])[F:9])[N:5]([CH2:11][C:12]([N:14]2[CH2:19][CH2:18][CH:17]([C:20]3[S:21][CH:22]=[C:23]([C:25]4[CH2:29][CH:28]([C:30]5[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=5[OH:36])[O:27][N:26]=4)[N:24]=3)[CH2:16][CH2:15]2)=[O:13])[N:4]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:44](Br)[CH:45]=[CH2:46].O>CC(C)=O>[CH2:46]([O:36][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=1[CH:28]1[O:27][N:26]=[C:25]([C:23]2[N:24]=[C:20]([CH:17]3[CH2:16][CH2:15][N:14]([C:12](=[O:13])[CH2:11][N:5]4[C:6]([CH:8]([F:10])[F:9])=[CH:7][C:3]([CH:2]([F:1])[F:37])=[N:4]4)[CH2:19][CH2:18]3)[S:21][CH:22]=2)[CH2:29]1)[CH:45]=[CH2:44]

Participants

6

Reactant 4

HCID 962WaterHCID 7841Allyl bromideHCID 11430Potassium CarbonateHCID 665846872-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]-1-(4-{4-[5-(2-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)ethanone

Product 1

HCID 672415851-[4-(4-{5-[2-(allyloxy)phenyl]-4,5-dihydro-1,2-oxazol-3-yl}-1,3-thiazol-2-yl)piperidin-1-yl]-2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethanoneYield 55.1%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of 2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]-1-(4-{4-[5-(2-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)ethanone (81 mg) and potassium carbonate (105 mg) in acetone (5 ml) is added, at room temperature, allyl bromide (73 mg). The reaction mixture is stirred at reflux for 5 h. Then the mixture is admixed with water and extracted with ethyl acetate. The combined organic phases are dried over sodium sulphate and concentrated. Purification by column chromatography gives 1-[4-(4-{5-[2-(allyloxy)phenyl]-4,5-dihydro-1,2-oxazol-3-yl}-1,3-thiazol-2-yl)piperidin-1-yl]-2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethanone (48 mg).

Workup

  1. temperatureat reflux for 5 h
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic phases are dried over sodium sulphate
  4. concentrationconcentrated
  5. customPurification by column chromatography

Sources & evidence

ORD record
ord-f5af5f4c60de445d909b2a6cddc16971
Source dataset
uspto-grants-2015_10
Patent number
US09167821B2

Reaction notes

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