Triethylamine → N-(4-(4-(4-(1,1,1,3,3,3-Hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazine-1-carbonyl)phenyl)-3-(1-methylcyclopropyl)propanamide

HRID 1807717Notes

Reaction equation

HRID 1807717 reaction equation
[CH3:1][C:2]1([CH2:5][CH2:6][C:7](Cl)=[O:8])[CH2:4][CH2:3]1.[NH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([N:19]2[CH2:24][CH2:23][N:22]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([C:32]([OH:41])([C:37]([F:40])([F:39])[F:38])[C:33]([F:36])([F:35])[F:34])=[CH:28][CH:27]=3)[CH2:21][CH2:20]2)=[O:18])=[CH:13][CH:12]=1.C(N(CC)CC)C>ClCCl>[F:39][C:37]([F:38])([F:40])[C:32]([C:29]1[CH:28]=[CH:27][C:26]([CH2:25][N:22]2[CH2:21][CH2:20][N:19]([C:17]([C:14]3[CH:15]=[CH:16][C:11]([NH:10][C:7](=[O:8])[CH2:6][CH2:5][C:2]4([CH3:1])[CH2:4][CH2:3]4)=[CH:12][CH:13]=3)=[O:18])[CH2:24][CH2:23]2)=[CH:31][CH:30]=1)([OH:41])[C:33]([F:36])([F:35])[F:34]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 583536463-(1-Methylcyclopropyl)propanoyl chlorideHCID 86638547(4-Aminophenyl)(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazin-1-yl)methanone

Product 1

HCID 86638548N-(4-(4-(4-(1,1,1,3,3,3-Hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazine-1-carbonyl)phenyl)-3-(1-methylcyclopropyl)propanamideYield 21.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-(1-Methylcyclopropyl)propionic acid (1.752 mmol, 0.2 g) was stirred in dichloromethane at 0° C. Oxalyl chloride (8.76 mmol, 0.752 mL, 1.112 g) was added and the reaction stirred overnight. The reaction mixture was concentrated under vacuum to give the intermediate 3-(1-methylcyclopropyl)propanoyl chloride. A mixture of 3-(1-methyl-cyclopropyl)propanoyl chloride (0.813 mmol, 0.119 g), (4-aminophenyl)(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazin-1-yl)methanone (0.542 mmol, 0.25 g) and triethylamine (1.084 mmol, 0.151 mL, 0.110 g) were stirred in dichloromethane at 0° C. for 1 hour. The reaction mixture was allowed to warm to room temperature. The reaction mixture was washed with water, concentrated under vacuum and purified by acidic prep HPLC to afford the title compound (67 mg). MS (ESI) m/z 572.3 [M+H]+

Workup

  1. washThe reaction mixture was washed with water
  2. concentrationconcentrated under vacuum
  3. custompurified by acidic prep HPLC

Sources & evidence

ORD record
ord-0dfd1e93236a440c8846432c87f32245
Source dataset
uspto-grants-2013_01
Patent number
US08357679B2

Reaction notes

Loading…