Water → 1-[4-[(ethylamino)carbonyl]-2-(1-phenylethoxy)phenyl]-N-cyclopropyl-1H-1,2,3-triazole-4-carboxamide

HRID 1717405Notes

Reaction equation

HRID 1717405 reaction equation
[CH2:1]([NH:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH:16]=[C:15]([C:17]([NH:19][CH:20]3[CH2:22][CH2:21]3)=[O:18])[N:14]=[N:13]2)=[C:8]([OH:23])[CH:7]=1)=[O:5])[CH3:2].Br[CH:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH3:26].C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[CH2:1]([NH:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH:16]=[C:15]([C:17]([NH:19][CH:20]3[CH2:22][CH2:21]3)=[O:18])[N:14]=[N:13]2)=[C:8]([O:23][CH:25]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH3:26])[CH:7]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 11454(1-Bromoethyl)benzeneHCID 576650001-{4-[(ethylamino)carbonyl]-2-hydroxyphenyl}-N-cyclopropyl-1H-1,2,3-triazole-4-carboxamide

Product 1

HCID 576648281-[4-[(ethylamino)carbonyl]-2-(1-phenylethoxy)phenyl]-N-cyclopropyl-1H-1,2,3-triazole-4-carboxamideYield 33.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution (500 μl; 70 μmol) of 1-{4-[(ethylamino)carbonyl]-2-hydroxyphenyl}-N-cyclopropyl-1H-1,2,3-triazole-4-carboxamide (0.14M) in DMF, and a solution (500 μl; 105 μmol) of (1-bromoethyl)benzene (0.21M) in DMF, and a powder of potassium carbonate (30 mg) were mixed at room temperature, and the mixture was stirred for 16 hr. Water (2 ml) was added to the reaction mixture, and the mixture was extracted with dichloromethane (3 ml). The solvent was evaporated under reduced pressure, and the residue was dissolved in DMSO (1 ml) and purified by preparative HPLC (Gilson, Inc., high-throughput purification system, column: YMC CombiPrep ODS-A S-5 μm, 50×20 mm, solvent: solution A; 0.1% formic acid aqueous solution, solution B; 0.1% formic acid acetonitrile solution, gradient cycle: 0 min (solution A/solution B=95/5), 1.00 min (solution A/solution B=95/5), 5.20 min (solution A/solution B=5/95), 6.40 min (solution A/solution B=5/95), 6.50 min (solution A/solution B=95/5), 6.60 min (solution A/solution B=95/5), flow rate: 25 ml/min, detection method: UV 220 nm) to give the title compound (9.8 mg) (LC/MS purity 100%, ESI+:420 [M+H]+).

Workup

  1. extractionthe mixture was extracted with dichloromethane (3 ml)
  2. customThe solvent was evaporated under reduced pressure
  3. dissolutionthe residue was dissolved in DMSO (1 ml)
  4. custompurified by preparative HPLC (Gilson, Inc., high-throughput purification system, column: YMC CombiPrep ODS-A S-5 μm, 50×20 mm, solvent: solution A; 0.1% formic acid aqueous solution, solution B; 0.1% formic acid acetonitrile solution, gradient cycle: 0 min (solution A/solution B=95/5), 1.00 min (solution A/solution B=95/5), 5.20 min (solution A/solution B=5/95), 6.40 min (solution A/solution B=5/95), 6.50 min (solution A/solution B=95/5), 6.60 min (solution A/solution B=95/5), flow rate: 25 ml/min, detection method: UV 220 nm)

Sources & evidence

ORD record
ord-0c6193354b6847d096fae2ed9923a2c8
Source dataset
uspto-grants-2010_09
Patent number
US07803822B2

Reaction notes

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