Sodium Carbonate → 4-[1-(2,4-dichlorophenyl)-3-[(4-hydroxy-4-phenylpiperidin-1-yl)carbonyl]-4-methyl-1H-pyrazol-5-yl]benzonitrile

HRID 2276890Notes

Reaction equation

HRID 2276890 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[Cl:20])[N:11]=[C:10]([C:21]([N:23]3[CH2:28][CH2:27][C:26]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)([OH:29])[CH2:25][CH2:24]3)=[O:22])[C:9]=2[CH3:36])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:43][N:44](C)C(=O)C>[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.[K+].[K+].[K+].[K+].[Fe+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:20][C:14]1[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:13]=1[N:12]1[C:8]([C:5]2[CH:6]=[CH:7][C:2]([C:43]#[N:44])=[CH:3][CH:4]=2)=[C:9]([CH3:36])[C:10]([C:21]([N:23]2[CH2:28][CH2:27][C:26]([OH:29])([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH2:25][CH2:24]2)=[O:22])=[N:11]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 31374DimethylacetamideHCID 71116150HCID 71116150, compound

Product 1

HCID 711161474-[1-(2,4-dichlorophenyl)-3-[(4-hydroxy-4-phenylpiperidin-1-yl)carbonyl]-4-methyl-1H-pyrazol-5-yl]benzonitrileYield 10%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 9605257Potassium FerrocyanideCatalyst

Conditions

Temperature
120 °C

Procedure

Nitrogen gas was bubbled through a solution of 1-{[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]carbonyl}-4-phenylpiperidin-4-ol (1 eq., 45 mg, 0.077 mmol), K4[Fe(CN)6].3H2O (0.22 eq., 7.5 mg, 0.017 mmol), sodium carbonate (1 eq., 8.1 mg, 0.017 mmol), and palladium(II) acetate (0.10 eq., 1.7 mg, 0.008 mmol) in N,N-dimethylacetamide (2 mL) for 1 min. The solution is capped and stirred at 120° C. for 16 h. The reaction was concentrated in vacuo. The crude reaction material was then purified by silica gel column chromatography using 0-100% ethyl acetate/hexane to yield pure 4-[1-(2,4-dichlorophenyl)-3-[(4-hydroxy-4-phenylpiperidin-1-yl)carbonyl]-4-methyl-1H-pyrazol-5-yl]benzonitrile (4 mg, 10%). 1H NMR (300 MHz, CHLOROFORM-d) d ppm 1.75-1.94 (m, 2H) 2.07-2.32 (m, 5H) 3.25-3.43 (m, 1H) 3.55-3.76 (m, 1H) 4.31 (d, J=12.90 Hz, 1H) 4.73 (d, J=13.00 Hz, 1H) 7.01 (d, J=8.48 Hz, 2H) 7.08-7.57 (m, 10H).

Workup

  1. customThe solution is capped
  2. concentrationThe reaction was concentrated in vacuo
  3. customThe crude reaction material
  4. customwas then purified by silica gel column chromatography

Sources & evidence

ORD record
ord-15b55ca6e5364b55a89a2e6d198638e5
Source dataset
uspto-grants-2015_09
Patent number
US09133128B2

Reaction notes

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