Water → 1-Propanesulfonic acid, 3,3,3-trifluoro-, 4-(2-(2,4-dichlorophenyl)-5-methyl-4-((1-piperidinylamino)carbonyl)-1H-imidazol-1-yl)phenyl ester

HRID 1715100Notes

Reaction equation

HRID 1715100 reaction equation
[N:1]1([NH:7][C:8]([C:10]2[N:11]=[C:12]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=3[Cl:30])[N:13]([C:16]3[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=3)[C:14]=2[CH3:15])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[F:38][C:39]([F:47])([F:46])[CH2:40][CH2:41][S:42](Cl)(=[O:44])=[O:43].O>ClCCl>[Cl:30][C:24]1[CH:25]=[C:26]([Cl:29])[CH:27]=[CH:28][C:23]=1[C:12]1[N:13]([C:16]2[CH:17]=[CH:18][C:19]([O:22][S:42]([CH2:41][CH2:40][C:39]([F:47])([F:46])[F:38])(=[O:44])=[O:43])=[CH:20][CH:21]=2)[C:14]([CH3:15])=[C:10]([C:8](=[O:9])[NH:7][N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[N:11]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471Triethylamine2×HCID 27611773,3,3-Trifluoropropane-1-sulfonyl chloride2×HCID 589650752-(2,4-Dichlorophenyl)-1-(4-hydroxyphenyl)-5-methyl-1H-imidazole-4-carboxylic acid piperidin-1-ylamide

Product 1

HCID 115489331-Propanesulfonic acid, 3,3,3-trifluoro-, 4-(2-(2,4-dichlorophenyl)-5-methyl-4-((1-piperidinylamino)carbonyl)-1H-imidazol-1-yl)phenyl esterYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

2-(2,4-Dichlorophenyl)-1-(4-hydroxyphenyl)-5-methyl-1H-imidazole-4-carboxylic piperidin-1-ylamide, from Ex 2, Step 1, (0.89 g, 2.00 mmol) was dissolved in dichloromethane (20 ml), cooled to 0° C. and triethylamine (0.35 ml, 2.4 mmol) added followed by 3,3,3-trifluoropropanesulfonyl chloride (prepared by an analogous method to that described in WO00/010968 for the butyl homologue) (0.35 ml, 2.40 mmol). The reaction mixture was stirred at room temperature overnight. TLC showed remaining starting material and so another portion of triethylamine and 3,3,3-trifluoropropanesulfonyl chloride was added and the reaction mixture stirred for additional 2 hrs. Water was added and the product was extracted with dichloromethane, dried (Na2SO4), filtered and concentrated. Flash chromatography (hexane:EtOAc 1:3-EtOAc) followed by recrystallization (hexane:EtOAc) afforded 700 mg (59%) of the title compound as a colorless solid.

Workup

  1. customprepared by an analogous method to
  2. stirringthe reaction mixture stirred for additional 2 hrs
  3. extractionthe product was extracted with dichloromethane
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customFlash chromatography (hexane:EtOAc 1:3-EtOAc) followed by recrystallization (hexane:EtOAc)

Sources & evidence

ORD record
ord-57c2d901627044f09d3890ae7a9f3524
Source dataset
uspto-grants-2010_09
Patent number
US07799804B2

Reaction notes

Loading…