Triethylamine → 1-{[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]carbonyl}-4-phenylpiperidine-4-carboxamide

HRID 2276885Notes

Reaction equation

HRID 2276885 reaction equation
[Br:1][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](O)=[O:22])[C:9]=2[CH3:24])=[CH:4][CH:3]=1.FC(F)(F)C([O-])=O.[C:32]([C:35]1([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH2:40][CH2:39][NH2+:38][CH2:37][CH2:36]1)(=[O:34])[NH2:33].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>O1CCCC1>[Br:1][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:38]3[CH2:37][CH2:36][C:35]([C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=4)([C:32]([NH2:33])=[O:34])[CH2:40][CH2:39]3)=[O:22])[C:9]=2[CH3:24])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 107173015-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acidHCID 867160534-Carbamoyl-4-phenylpiperidin-1-ium trifluoroacetate

Product 1

HCID 711161671-{[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]carbonyl}-4-phenylpiperidine-4-carboxamideYield 52.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid (1 eq, 130 mg, 0.306 mmol), 4-carbamoyl-4-phenylpiperidin-1-ium trifluoroacetate (1.1 eq, 69 mg, 0.337 mmol), benzotriazole-1-yl-oxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) (1.1 eq., 149 mg, 0.337 mmol), and triethylamine (3 eq, 0.13 mL, 0.92 mmol) was stirred in tetrahydrofuran (5 mL) 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 1-{[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]carbonyl}-4-phenylpiperidine-4-carboxamide (98 mg, 52%). 1H NMR (300 MHz, CHLOROFORM-d) d ppm 2.10 (dd, J=9.75, 3.63 Hz, 1H) 2.18 (s, 3H) 2.20-2.28 (m, 1H) 2.46 (d, J=14.03 Hz, 2H) 3.65 (t, J=10.31 Hz, 1H) 3.75-3.88 (m, 1H) 3.95-4.07 (m, 1H) 4.15-4.28 (m, 1H) 5.17-5.50 (m, 2H) 7.00 (d, J=8.38 Hz, 2H) 7.12-7.50 (m, 10H).

Workup

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

Sources & evidence

ORD record
ord-1ad226db6a0f4d189db6729fc4fe3366
Source dataset
uspto-grants-2015_09
Patent number
US09133128B2

Reaction notes

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