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

HRID 238658Notes

Reaction equation

HRID 238658 reaction equation
[CH:1](=[N:8][OH:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClN1C(=O)CCC1=O.[CH:18]([C:20]1[N:21]=[C:22]([CH:25]2[CH2:30][CH2:29][N:28]([C:31](=[O:43])[CH2:32][N:33]3[C:37]([CH3:38])=[CH:36][C:35]([C:39]([F:42])([F:41])[F:40])=[N:34]3)[CH2:27][CH2:26]2)[S:23][CH:24]=1)=[CH2:19].C(N(CC)CC)C>CN(C)C=O.O>[C:2]1([C:1]2[CH2:19][CH:18]([C:20]3[N:21]=[C:22]([CH:25]4[CH2:30][CH2:29][N:28]([C:31](=[O:43])[CH2:32][N:33]5[C:37]([CH3:38])=[CH:36][C:35]([C:39]([F:41])([F:40])[F:42])=[N:34]5)[CH2:27][CH2:26]4)[S:23][CH:24]=3)[O:9][N:8]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 12143(Z)-Benzaldehyde oximeHCID 31398ChlorosuccinimideHCID 687425534-(4-ethenyl-2-thiazolyl)-1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]piperidine2×

Product 1

HCID 687452054-[4-(4,5-dihydro-3-phenyl-5-isoxazolyl)-2-thiazolyl]-1-[(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetyl]piperidine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of benzaldehyde oxime (49 mg, 0.4 mmol) in N,N-dimethylformamide (3 mL) was added N-chlorosuccinimide (54 mg, 0.4 mmol), followed by addition of 4-(4-ethenyl-2-thiazolyl)-1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]piperidine (i.e. the product of Example 4, Step C) (103 mg, 0.27 mmol) and triethylamine (41 mg, 0.4 mmol). The resulting mixture was stirred at room temperature for 5 h, then diluted with water, extracted with dichloromethane (2×). The organic layers were combined and dried (MgSO4), and filtered. The filtrate was concentrated, and the residue was purified by column chromatography on silica gel using 55-70% ethyl acetate in hexanes as eluant to give 90 mg of the title product, a compound of the present invention as a white solid.

Workup

  1. extractionextracted with dichloromethane (2×)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. customthe residue was purified by column chromatography on silica gel using 55-70% ethyl acetate in hexanes as eluant

Sources & evidence

ORD record
ord-6fd48b9f551b4b158331a284fad7772f
Source dataset
uspto-grants-2014_02
Patent number
US08642634B2

Reaction notes

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