Potassium Carbonate → 4-(4-Hydroxy-4-phenylpiperidin-1-yl)-1-{[3-(trifluoromethyl)-1H-pyrazol-1-yl]methyl}-1,3,5-triazin-2(1H)-one

HRID 1477615Notes

Reaction equation

HRID 1477615 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:21])[CH2:13][CH2:12][N:11]([C:14]3[N:19]=[CH:18][NH:17][C:16](=[O:20])[N:15]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.OC1(C2C=CC=CC=2)CCN(C2N=CNC(=O)N=2)CC1.CC1C=CC(S(O[CH2:53][N:54]2[CH:58]=[CH:57][C:56]([C:59]([F:62])([F:61])[F:60])=[N:55]2)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+]>O.CN(C)C=O>[OH:21][C:8]1([C:5]2[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=2)[CH2:13][CH2:12][N:11]([C:14]2[N:19]=[CH:18][N:17]([CH2:53][N:54]3[CH:58]=[CH:57][C:56]([C:59]([F:62])([F:61])[F:60])=[N:55]3)[C:16](=[O:20])[N:15]=2)[CH2:10][CH2:9]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 117839328[3-(Trifluoromethyl)-1H-pyrazol-1-yl]methyl 4-methylbenzenesulfonateHCID 178517888HCID 178517888, compoundHCID 178517889HCID 178517889, compound

Product 1

HCID 1178396584-(4-Hydroxy-4-phenylpiperidin-1-yl)-1-{[3-(trifluoromethyl)-1H-pyrazol-1-yl]methyl}-1,3,5-triazin-2(1H)-oneYield 6.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

An N,N-dimethylformamide suspension (1.4 mL) of a mixture of 4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1,3,5-triazin-2(1H)-one synthesized in Reference Synthesis Example 22a and 4-(4-hydroxy-4-phenylpiperidin-1-yl)-1,3,5-triazin-2(1H)-one (140 mg), [3-(trifluoromethyl)-1H-pyrazol-1-yl]methyl 4-methylbenzenesulfonate (282 mg, 0.91 mmol) synthesized in Reference Synthesis Example 15, and potassium carbonate (252 mg, 1.83 mmol) was stirred at 80° C. for 3 hours. After completion of the reaction, water was added thereto and extraction with ethyl acetate from the resultant mixture was performed. The obtained organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/4 (v/v)) and preparative high-performance liquid chromatography to obtain the title compound (14 mg, yield 6.8%) in Reference Synthesis Example 91a and the title compound (7.4 mg, yield 3.9%) in Reference Synthesis Example 91b.

Workup

  1. additionwas added
  2. extractionextraction with ethyl acetate from the resultant mixture
  3. washThe obtained organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/4 (v/v))

Sources & evidence

ORD record
ord-314900cfc4854deb997cd1595709ab18
Source dataset
uspto-grants-2016_08
Patent number
US09403798B2

Reaction notes

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