Triethylamine → 1-[[5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]carbonyl]-4-phenyl-4-piperidinecarboxylic acid

HRID 2276880Notes

Reaction equation

HRID 2276880 reaction equation
C(Cl)(=O)C(Cl)=O.[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:18]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=3[Cl:26])[N:17]=[C:16]([C:27](O)=[O:28])[C:15]=2[CH3:30])=[CH:10][CH:9]=1.C(N(CC)CC)C.[Cl-].[C:39]([C:42]1([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[CH2:47][CH2:46][NH2+:45][CH2:44][CH2:43]1)([OH:41])=[O:40]>ClCCl.CN(C)C=O>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[N:18]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=3[Cl:26])[N:17]=[C:16]([C:27]([N:45]3[CH2:44][CH2:43][C:42]([C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)([C:39]([OH:41])=[O:40])[CH2:47][CH2:46]3)=[O:28])[C:15]=2[CH3:30])=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 15194215-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acidHCID 178524006HCID 178524006, compound

Product 1

HCID 573427121-[[5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]carbonyl]-4-phenyl-4-piperidinecarboxylic acidYield 67%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A 2 M solution of oxalyl chloride in dichloromethane (3 eq., 0.19 mL, 0.377 mmol) was added to 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid (1 eq., 48 mg, 0.126 mmol) in dichloromethane (5 mL). Next, 2 drops of anhydrous N,N-dimethylformamide was added the reaction was stirred for 2 h. The reaction was concentrated in vacuo. The reaction mixture was dissolved in dichloromethane (5 mL). Triethylamine (3 eq., 0.05 mL, 0.377 mmol) and 4-carboxy-4-phenylpiperidin-1-ium chloride (1.5 eq., 45.7 mg, 0.189 mmol) was added and the reaction was stirred for 16 h. The reaction was concentrated in vacuo. The crude reaction material was then purified by silica gel column chromatography using 0-10% methanol/dichloromethane with 1% acetic acid to yield pure 1-{[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]carbonyl}-4-phenylpiperidine-4-carboxylic acid (48 mg, 67%). (77) 1H NMR (300 MHz, CHLOROFORM-d) d ppm 1.87-2.09 (m, 2H) 2.15 (s, 3H) 2.61 (t, J=16.18 Hz, 2H) 3.21 (t, J=12.03 Hz, 1H) 3.47 (t, J=11.94 Hz, 1H) 4.26 (d, J=13.61 Hz, 1H) 4.57 (d, J=13.56 Hz, 1H) 7.05 (d, J=8.34 Hz, 2H) 7.12-7.45 (m, 10H).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. dissolutionThe reaction mixture was dissolved in dichloromethane (5 mL)
  3. stirringthe reaction was stirred for 16 h
  4. concentrationThe reaction was concentrated in vacuo
  5. customThe crude reaction material
  6. customwas then purified by silica gel column chromatography

Sources & evidence

ORD record
ord-afde8f781a5e400692cf887db0dea8dc
Source dataset
uspto-grants-2015_09
Patent number
US09133128B2

Reaction notes

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