Hydrochloric Acid → 8-[(2,6-difluorobenzyl)oxy]-N-[1-hydroxy-2-(hydroxymethyl)hexan-2-yl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide

HRID 64493Notes

Reaction equation

HRID 64493 reaction equation
[CH2:1]([C:5]([NH:16][C:17]([C:19]1[N:23]2[CH:24]=[CH:25][CH:26]=[C:27]([O:28][CH2:29][C:30]3[C:35]([F:36])=[CH:34][CH:33]=[CH:32][C:31]=3[F:37])[C:22]2=[N:21][C:20]=1[CH3:38])=[O:18])([C:11](OCC)=[O:12])[C:6](OCC)=[O:7])[CH2:2][CH2:3][CH3:4].[Cl-].[Ca+2].[Cl-].[BH4-].[Na+].Cl>C(O)C.O.C(OCC)(=O)C>[F:37][C:31]1[CH:32]=[CH:33][CH:34]=[C:35]([F:36])[C:30]=1[CH2:29][O:28][C:27]1[C:22]2[N:23]([C:19]([C:17]([NH:16][C:5]([CH2:6][OH:7])([CH2:1][CH2:2][CH2:3][CH3:4])[CH2:11][OH:12])=[O:18])=[C:20]([CH3:38])[N:21]=2)[CH:24]=[CH:25][CH:26]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydride3×HCID 5284359Calcium Chloride3×HCID 86713527Diethyl butyl[({8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridin-3-yl}carbonyl)amino]malonate

Product 1

HCID 867135298-[(2,6-difluorobenzyl)oxy]-N-[1-hydroxy-2-(hydroxymethyl)hexan-2-yl]-2-methylimidazo[1,2-a]pyridine-3-carboxamideYield 55.9%

Reagents, catalysts & solvents 3

HCID 702EthanolSolvent2×HCID 962WaterSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 68 mg of diethyl butyl[({8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridin-3-yl}carbonyl)amino]malonate in 1.4 ml of ethanol was added a solution of 35 mg of calcium chloride in 0.34 ml of water. Subsequently, 24 mg of sodium borohydride was added thereto under ice-cooling, followed by stirring for 1 hour under ice-cooling and at room temperature for 4 hours. Further, 2 ml of ethanol, a solution of 35 mg of calcium chloride in 0.34 ml of water, and 24 mg of sodium borohydride were added thereto followed by stirring at room temperature for 15 hours. Further, a solution of 35 mg of calcium chloride in 0.34 ml of water and 24 mg of sodium borohydride were added thereto, followed by stirring at room temperature for 15 hours. To the reaction mixture were added 1 M hydrochloric acid and ethyl acetate to carry out a layer separation operation. The organic layer was washed with saturated brine and 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 32 mg of 8-[(2,6-difluorobenzyl)oxy]-N-[1-hydroxy-2-(hydroxymethyl)hexan-2-yl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide.

Workup

  1. temperatureunder ice-cooling
  2. stirringby stirring at room temperature for 15 hours
  3. stirringby stirring at room temperature for 15 hours
  4. customa layer separation operation
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-d0616effa4ea4c99b16014b5288f5bf4
Source dataset
uspto-grants-2016_09
Patent number
US09447090B2

Reaction notes

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