Dimethylformamide → 2,6-difluoro-4-methoxy-N-[4-(6-methylimidazo[1,2-a]pyridin-2-yl)phenyl]benzamide

HRID 339572Notes

Reaction equation

HRID 339572 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([F:13])[C:3]=1[C:4]([OH:6])=O.CN(C=O)C.[CH3:19][C:20]1[CH:21]=[CH:22][C:23]2[N:24]([CH:26]=[C:27]([C:29]3[CH:35]=[CH:34][C:32]([NH2:33])=[CH:31][CH:30]=3)[N:28]=2)[CH:25]=1.CCOC(C)=O.CCCCCC>S(Cl)(Cl)=O.N1C=CC=CC=1>[F:13][C:7]1[CH:8]=[C:9]([O:11][CH3:12])[CH:10]=[C:2]([F:1])[C:3]=1[C:4]([NH:33][C:32]1[CH:31]=[CH:30][C:29]([C:27]2[N:28]=[C:23]3[CH:22]=[CH:21][C:20]([CH3:19])=[CH:25][N:24]3[CH:26]=2)=[CH:35][CH:34]=1)=[O:6]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8210844-(6-Methylimidazo[1,2-a]pyridin-2-yl)anilineHCID 27782282,6-Difluoro-4-methoxybenzoic acidHCID 21226206Ethyl acetate hexane

Product 1

HCID 583421752,6-difluoro-4-methoxy-N-[4-(6-methylimidazo[1,2-a]pyridin-2-yl)phenyl]benzamideYield 45.5%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 24386Thionyl ChlorideSolvent

Procedure

To a stirred solution of 2,6-difluoro-4-methoxybenzoic acid (0.25 g, 1.34 mmol) in thionyl chloride (7 ml) was added a drop of DMF and the reaction mixture was then heated under reflux for 3 h. On cooling to room temperature the excess reagent was removed under reduced pressure to give a crude residue. The amide was prepared as described in the Amide Coupling section using of the crude residue and 4-(6-methylimidazo[1,2-a]pyridin-2-yl)aniline (0.30 g, 1.34 mmol) in dry pyridine (15 ml) to give the title compound (0.24 g, 45%) as a pale yellow solid after work-up and flash chromatography (2:1 EtOAc/Hexane followed by EtOAc then MeOH).

Workup

  1. temperaturethe reaction mixture was then heated
  2. temperatureunder reflux for 3 h
  3. customwas removed under reduced pressure
  4. customto give a crude residue
  5. customThe amide was prepared

Sources & evidence

ORD record
ord-9b74a63aa14a4fe382d6617fd512960a
Source dataset
uspto-grants-2014_11
Patent number
US08895313B2

Reaction notes

Loading…