Citric Acid → Diethyl butyl[({8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridin-3-yl}carbonyl)amino]malonate

HRID 64492

Reaction equation

HRID 64492 reaction equation
[CH2:1]([O:3][C:4](=[O:34])[CH:5]([NH:11][C:12]([C:14]1[N:18]2[CH:19]=[CH:20][CH:21]=[C:22]([O:23][CH2:24][C:25]3[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=3[F:32])[C:17]2=[N:16][C:15]=1[CH3:33])=[O:13])[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:2].[O-]CC.[Na+].C(O)C.I[CH2:43][CH2:44][CH2:45][CH3:46].[O-]CC.[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.C(O)C>[CH2:43]([C:5]([NH:11][C:12]([C:14]1[N:18]2[CH:19]=[CH:20][CH:21]=[C:22]([O:23][CH2:24][C:25]3[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=3[F:32])[C:17]2=[N:16][C:15]=1[CH3:33])=[O:13])([C:4]([O:3][CH2:1][CH3:2])=[O:34])[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH2:44][CH2:45][CH3:46]

Participants

9

Reactant 6

HCID 311Citric AcidHCID 10962Butyl iodideHCID 516892Sodium BicarbonateHCID 2723922Sodium ethoxideHCID 23706232Ethanol sodium ethoxideHCID 86713528Diethyl[({8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridin-3-yl}carbonyl)amino]malonate

Product 1

HCID 86713527Diethyl butyl[({8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridin-3-yl}carbonyl)amino]malonate

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6212ChloroformSolvent

Conditions

Temperature
70 °C

Procedure

To 252 mg of diethyl[({8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridin-3-yl}carbonyl)amino]malonate were added 4 ml of ethanol, 0.23 ml of a 20% sodium ethoxide/ethanol solution, and 0.31 ml of 1-iodobutane, followed by stirring at 70° C. for 3 hours. Subsequently, 11 mg of sodium ethoxide was added thereto, followed by stirring at 70° C. for 1 hour. To the reaction mixture were added an aqueous citric acid solution, a saturated aqueous sodium hydrogen carbonate solution, and chloroform to carry out a layer separation operation. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 69 mg of diethyl butyl[({8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridin-3-yl}carbonyl)amino]malonate.

Workup

  1. stirringby stirring at 70° C. for 1 hour
  2. customa layer separation operation
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-af7d2113700a453d8a8cb158194c14ec
Source dataset
uspto-grants-2016_09
Patent number
US09447090B2

Linked notes

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