Diisopropylethylamine → 1-({2-[1-tert-butyl-5-(4-fluorophenyl)-1H-pyrazol-4-yl]-1,3-thiazol-4-yl}acetyl)piperidin-4-one

HRID 1750345Notes

Reaction equation

HRID 1750345 reaction equation
[C:1]([N:5]1[C:9]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)=[C:8]([C:17]2[S:18][CH:19]=[C:20]([CH2:22][C:23](O)=[O:24])[N:21]=2)[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.O.Cl.[NH:61]1[CH2:66][CH2:65][C:64](=[O:67])[CH2:63][CH2:62]1>CN(C=O)C.O>[C:1]([N:5]1[C:9]([C:10]2[CH:11]=[CH:12][C:13]([F:16])=[CH:14][CH:15]=2)=[C:8]([C:17]2[S:18][CH:19]=[C:20]([CH2:22][C:23]([N:61]3[CH2:66][CH2:65][C:64](=[O:67])[CH2:63][CH2:62]3)=[O:24])[N:21]=2)[CH:7]=[N:6]1)([CH3:3])([CH3:2])[CH3:4]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2723901PiperonylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867211822-(2-(1-tert-butyl-5-(4-fluorophenyl)-1H-pyrazol-4-yl)thiazol-4-yl)acetic acid

Product 1

HCID 867211831-({2-[1-tert-butyl-5-(4-fluorophenyl)-1H-pyrazol-4-yl]-1,3-thiazol-4-yl}acetyl)piperidin-4-oneYield 60%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of the compound (60 mg, 0.17 mmol) obtained in step 6, HATU (76 mg, 0.20 mmol), DIEA (0.035 mL, 0.20 mmol) and piperidin-4-one monohydrochloride monohydrate (30.8 mg, 0.20 mmol) in DMF (1.5 mL) was stirred at room temperature for 4 hr. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 5→100% ethyl acetate/hexane) to give the title compound (44 mg, 0.100 mmol, 60%) as a white powder.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water and saturated brine
  3. customdried
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 5→100% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-2fdb94dfbcd84cf2a725b7855591916e
Source dataset
uspto-grants-2015_10
Patent number
US09156837B2

Reaction notes

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