Ethyl Acetate → 2-[3,5-Bis(difluoromethyl)-1H-pyrazol-1-yl]-1-(4-{4-[5-(2-ethynylphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)ethanone

HRID 1770384Notes

Reaction equation

HRID 1770384 reaction equation
C(N[C:5]1[CH:10]=[CH:9][C:8](S(N=[N+]=[N-])(=O)=O)=[CH:7][CH:6]=1)(=O)C.O=[C:18](C)[CH2:19]P(=O)(OC)OC.[F:27][CH:28]([F:64])[C:29]1[CH:33]=[C:32]([CH:34]([F:36])[F:35])[N:31]([CH2:37][C:38]([N:40]2[CH2:45][CH2:44][CH:43]([C:46]3[S:47][CH:48]=[C:49]([C:51]4[CH2:55][CH:54](C5C=CC=CC=5C=O)[O:53][N:52]=4)[N:50]=3)[CH2:42][CH2:41]2)=[O:39])[N:30]=1.C(OCC)(=O)C>C(#N)C.CO.O>[F:64][CH:28]([F:27])[C:29]1[CH:33]=[C:32]([CH:34]([F:36])[F:35])[N:31]([CH2:37][C:38]([N:40]2[CH2:45][CH2:44][CH:43]([C:46]3[S:47][CH:48]=[C:49]([C:51]4[CH2:55][CH:54]([C:5]5[CH:6]=[CH:7][CH:8]=[CH:9][C:10]=5[C:18]#[CH:19])[O:53][N:52]=4)[N:50]=3)[CH2:42][CH2:41]2)=[O:39])[N:30]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 77872Dimethyl (2-oxopropyl)phosphonateHCID 51291854-Acetamidobenzenesulfonyl azideHCID 866575662-{3-[2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazol-4-yl]-4,5-dihydro-1,2-oxazol-5-yl}-benzaldehyde

Product 1

HCID 866575652-[3,5-Bis(difluoromethyl)-1H-pyrazol-1-yl]-1-(4-{4-[5-(2-ethynylphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)ethanone

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 4-acetamidobenzenesulphonyl azide (140 mg) in acetonitrile (10 ml) was added, at room temperature, dimethyl 2-oxopropylphosphonate (97 mg). After stirring for 2 hours, 2-{3-[2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazol-4-yl]-4,5-dihydro-1,2-oxazol-5-yl}benzaldehyde (267 mg) in methanol (2 ml) was added to the reaction mixture. After stirring for 8 hours, the reaction mixture was admixed with ethyl acetate and water and extracted with ethyl acetate. The organic extracts were dried over sodium sulphate and concentrated under reduced pressure. The residue was purified by chromatography. This gave tert-2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]-1-(4-{4-[5-(2-ethynylphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)ethanone (50 mg).

Workup

  1. stirringAfter stirring for 8 hours
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic extracts were dried over sodium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by chromatography

Sources & evidence

ORD record
ord-dd4a76f51c5c49f09becc78f1c1f6e49
Source dataset
uspto-grants-2016_02
Patent number
US09247748B2

Reaction notes

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