Water → 5-chloro-3-(4,4-difluorocyclohexylmethyl)-N-phenyl-2-trifluoromethylimidazo[1,2-a]pyridine-7-carboxamide

HRID 1468287Notes

Reaction equation

HRID 1468287 reaction equation
[Cl:1][C:2]1[N:7]2[C:8]([CH2:15][CH:16]3[CH2:21][CH2:20][C:19]([F:23])([F:22])[CH2:18][CH2:17]3)=[C:9]([C:11]([F:14])([F:13])[F:12])[N:10]=[C:6]2[CH:5]=[C:4]([C:24]([OH:26])=O)[CH:3]=1.CCN=C=NCCCN(C)C.Cl.[CH:39]1[CH:40]=[CH:41][C:42]2N(O)N=[N:45][C:43]=2[CH:44]=1.O.NC1C=CC=CC=1>CN(C=O)C>[Cl:1][C:2]1[N:7]2[C:8]([CH2:15][CH:16]3[CH2:21][CH2:20][C:19]([F:22])([F:23])[CH2:18][CH2:17]3)=[C:9]([C:11]([F:14])([F:12])[F:13])[N:10]=[C:6]2[CH:5]=[C:4]([C:24]([NH:45][C:43]2[CH:44]=[CH:39][CH:40]=[CH:41][CH:42]=2)=[O:26])[CH:3]=1

Participants

7

Reactant 5

HCID 962WaterHCID 6115AnilineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 867100955-Chloro-3-(4,4-difluorocyclohexylmethyl)-2-trifluoromethylimidazo[1,2-a]pyridine-7-carboxylic acid

Product 1

HCID 867100965-chloro-3-(4,4-difluorocyclohexylmethyl)-N-phenyl-2-trifluoromethylimidazo[1,2-a]pyridine-7-carboxamideYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A part of the crude product of 5-chloro-3-(4,4-difluorocyclohexylmethyl)-2-trifluoromethylimidazo[1,2-a]pyridine-7-carboxylic acid obtained in step 3 (28 mg) was dissolved in DMF (2.0 mL), and the solution was stirred overnight at room temperature after adding EDC.HCl (27 mg, 0.141 mmol), HOBt.H2O (22 mg, 0.141 mmol), and aniline (13 mg, 0.141 mmol). The reaction mixture was extracted with ethyl acetate after adding a sodium hydrogen carbonate aqueous solution. The organic layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was then evaporated under reduced pressure. The residue was purified by preparative thin-layer chromatography (chloroform/methanol=9/1) to give 5-chloro-3-(4,4-difluorocyclohexylmethyl)-N-phenyl-2-trifluoromethylimidazo[1,2-a]pyridine-7-carboxamide (18.0 mg, two-step yield 62%).

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate
  2. additionafter adding a sodium hydrogen carbonate aqueous solution
  3. washThe organic layer was washed with water and saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was then evaporated under reduced pressure
  6. customThe residue was purified by preparative thin-layer chromatography (chloroform/methanol=9/1)

Sources & evidence

ORD record
ord-039b3402046346d294fd5588e9060bea
Source dataset
uspto-grants-2015_04
Patent number
US09000186B2

Reaction notes

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