Triethylamine → tert-butyl N-(1-{[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]carbonyl}-4-phenylpiperidin-4-yl)carbamate

HRID 2276886Notes

Reaction equation

HRID 2276886 reaction equation
[Cl: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.C(N(CC)CC)C.[C:32]1([C:38]2([NH:44][C:45](=[O:51])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48])[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][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:41]3[CH2:42][CH2:43][C:38]([NH:44][C:45](=[O:51])[O:46][C:47]([CH3:48])([CH3:50])[CH3:49])([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH2:39][CH2:40]3)=[O:22])[C:9]=2[CH3:24])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 15194215-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acidHCID 9903704tert-butyl N-(4-phenylpiperidin-4-yl)carbamate

Product 1

HCID 57342881tert-butyl N-(1-{[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]carbonyl}-4-phenylpiperidin-4-yl)carbamateYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid (1 eq., 201 mg, 0.53 mmol), triethylamine (3 eq, 0.22 mL, 0.157 mmol), tert-butyl N-(4-phenyl piperidin-4-yl)carbamate (1 eq, 146 mg, 0.53 mmol), and Benzotriazole-1-yl-oxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) (1 eq, 233 mg, 0.53 mmol) was stirred in tetrahydrofuran (10 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 tert-butyl N-(1-{[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]carbonyl}-4-phenylpiperidin-4-yl)carbamate (295 mg, 87%). 1H NMR (300 MHz, CHLOROFORM-d) d ppm 1.37 (br. s., 9H) 2.11 (dd, J=12.67, 4.00 Hz, 2H) 2.21 (s, 3H) 2.24-2.34 (m, 1H) 2.34-2.56 (m, 1H) 3.26 (t, J=12.01 Hz, 1H) 3.56 (t, J=12.39 Hz, 1H) 4.32 (d, J=13.75 Hz, 1H) 4.64 (d, J=13.56 Hz, 1H) 4.96 (br. s., 1H) 7.08 (d, J=8.38 Hz, 2H) 7.13-7.49 (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-fb9ec3aadbb34d289d0583e3428d6a54
Source dataset
uspto-grants-2015_09
Patent number
US09133128B2

Reaction notes

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