Triethylamine → 1-[3-(1-Methyl-1H-tetrazol-5-yl)-phenyl]-3-{1-[2-(4-trifluoromethylphenyl)-ethyl]-piperidin-3-ylmethyl}-urea

HRID 896527Notes

Reaction equation

HRID 896527 reaction equation
Cl.[CH3:2][N:3]1[C:7]([C:8]2[CH:9]=[C:10]([NH:14][C:15]([NH:17][CH2:18][CH:19]3[CH2:24][CH2:23][CH2:22][NH:21][CH2:20]3)=[O:16])[CH:11]=[CH:12][CH:13]=2)=[N:6][N:5]=[N:4]1.[F:25][C:26]([F:47])([F:46])[C:27]1[CH:32]=[CH:31][C:30]([CH2:33][CH2:34]OS(C2C=CC(C)=CC=2)(=O)=O)=[CH:29][CH:28]=1.C(N(CC)CC)C>C(#N)C>[CH3:2][N:3]1[C:7]([C:8]2[CH:9]=[C:10]([NH:14][C:15]([NH:17][CH2:18][CH:19]3[CH2:24][CH2:23][CH2:22][N:21]([CH2:34][CH2:33][C:30]4[CH:29]=[CH:28][C:27]([C:26]([F:25])([F:46])[F:47])=[CH:32][CH:31]=4)[CH2:20]3)=[O:16])[CH:11]=[CH:12][CH:13]=2)=[N:6][N:5]=[N:4]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 18411913HCID 18411913, compoundHCID 223502531-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-3-piperidin-3-ylmethylurea hydrochloride

Product 1

HCID 100741821-[3-(1-Methyl-1H-tetrazol-5-yl)-phenyl]-3-{1-[2-(4-trifluoromethylphenyl)-ethyl]-piperidin-3-ylmethyl}-ureaYield 45%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 1-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-3-piperidin-3-ylmethylurea hydrochloride (50 mg, 142 μmol), toluene-4-sulfonic acid 2-(4-trifluoromethyl-phenyl)-ethyl ester (90% pure, 55 mg, 142 μmol), triethylamine (60 μL, 426 μmol) and acetonitrile (1.5 mL) was heated at reflux for 16.5 hours and cooled to room temperature. The mixture was concentrated, and the residue was purified by flash chromatography, eluting with 3% methanol in dichloromethane containing 0.3% aqueous ammonium hydroxide, to provide a white amorphous solid (30 mg, 45%). 1H NMR (300 MHz, CDCl3) δ8.26 (s, !H), 7.87 (d, J=8 Hz, 1H), 7.76 (s, 1H), 7.51 (d, J=8 Hz, 1H), 7.39 (t, J=8 Hz, 1H), 7.28 (d, J=8 Hz, 2H), 7.20 (d, J=8 Hz, 1H), 6.06 (bm, 1H), 4.15 (s, 3H), 3.23 (t, J=6 Hz, 2H), 3.03 (m, 1H), 2.86 (m, 2H), 2.61 (m, 2H), 2.1-1.5 (m, 7H), 1.05 (m, 1H). Mass spec (ES+) m/z 488.5 (M+H+, 100%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 16.5 hours
  3. concentrationThe mixture was concentrated
  4. customthe residue was purified by flash chromatography
  5. washeluting with 3% methanol in dichloromethane containing 0.3% aqueous ammonium hydroxide

Sources & evidence

ORD record
ord-671c3ec367984e7ba27371941bcb3f56
Source dataset
uspto-grants-2005_07
Patent number
US06919356B2

Reaction notes

Loading…