Water → HCID 86721271, compound

HRID 1750429Notes

Reaction equation

HRID 1750429 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][N:11]=[CH:10][C:9]=2[C:13]2[S:14][CH:15]=[C:16]([CH2:18][C:19]([NH:21][CH2:22][CH:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)=[O:20])[N:17]=2)=[CH:4][CH:3]=1.Br[CH2:30][CH:31]1[CH2:34][CH2:33][CH2:32]1.C(=O)([O-])[O-].[K+].[K+].O>C(#N)C>[CH:31]1([CH2:30][N:12]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)=[C:9]([C:13]3[S:14][CH:15]=[C:16]([CH2:18][C:19]([NH:21][CH2:22][CH:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)=[O:20])[N:17]=3)[CH:10]=[N:11]2)[CH2:34][CH2:33][CH2:32]1.[CH:31]1([CH2:30][N:11]2[CH:10]=[C:9]([C:13]3[S:14][CH:15]=[C:16]([CH2:18][C:19]([NH:21][CH2:22][CH:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)=[O:20])[N:17]=3)[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)=[N:12]2)[CH2:34][CH2:33][CH2:32]1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium Carbonate2×HCID 2734658(Bromomethyl)cyclobutane2×HCID 86721270HCID 86721270, compound

Product 2

HCID 86721271HCID 86721271, compoundHCID 86721272HCID 86721272, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 2-{2-[5-(4-fluorophenyl)-1H-pyrazol-4-yl]-1,3-thiazol-4-yl}-N-(tetrahydro-2H-pyran-4-ylmethyl)acetamide (58 mg, 0.14 mmol), (bromomethyl)cyclobutane (0.033 mL, 0.29 mmol) and potassium carbonate (40.0 mg, 0.29 mmol) in acetonitrile (3 mL) was stirred at 80° C. for 1 hr. To the reaction mixture were further added potassium carbonate (40.0 mg, 0.29 mmol) and (bromomethyl)cyclobutane (0.033 mL, 0.29 mmol), and the mixture was further stirred at 80° C. for 2 hr. Water was added to the reaction mixture, 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 NH-silica gel column chromatography (solvent gradient; 30→90% ethyl acetate/hexane) to give a mixture (1:3 (mol/mol), 55 mg, 0.118 mmol, 84%) of the title compound and 2-(2-(1-(cyclobutylmethyl)-3-(4-fluorophenyl)-1H-pyrazol-4-yl)thiazol-4-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide as a pale-yellow solid.

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 NH-silica gel column chromatography (solvent gradient; 30→90% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-692b5e31f0e7468facfad00ecb5b3ac4
Source dataset
uspto-grants-2015_10
Patent number
US09156837B2

Reaction notes

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