4-Methylmorpholine → 8-[(2-fluorobenzyl)oxy]-6-(hydroxymethyl)-N-[(1R)-2-hydroxy-1-phenylethyl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide

HRID 64473Notes

Reaction equation

HRID 64473 reaction equation
[F:1][C:2]1[CH:34]=[CH:33][CH:32]=[CH:31][C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:15]([C:19](=[O:30])[NH:20][C@H:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:22][OH:23])=[C:16]([CH3:18])[N:17]=2)[CH:9]=[C:10]([C:12](O)=[O:13])[CH:11]=1.CN1CCOCC1.ClC(OCC(C)C)=O>C(COC)OC>[F:1][C:2]1[CH:34]=[CH:33][CH:32]=[CH:31][C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:15]([C:19]([NH:20][C@H:21]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH2:22][OH:23])=[O:30])=[C:16]([CH3:18])[N:17]=2)[CH:9]=[C:10]([CH2:12][OH:13])[CH:11]=1

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 867135018-[(2-fluorobenzyl)oxy]-3-{[(1R)-2-hydroxy-1-phenylethyl]carbamoyl}-2-methylimidazo[1,2-a]pyridine-6-carboxylic acid

Product 1

HCID 867135008-[(2-fluorobenzyl)oxy]-6-(hydroxymethyl)-N-[(1R)-2-hydroxy-1-phenylethyl]-2-methylimidazo[1,2-a]pyridine-3-carboxamideYield 21.7%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

To a mixture of 100 mg of 8-[(2-fluorobenzyl)oxy]-3-{[(1R)-2-hydroxy-1-phenylethyl]carbamoyl}-2-methylimidazo[1,2-a]pyridine-6-carboxylic acid, 28 μl of 4-methylmorpholine, and 0.7 ml of dimethoxyethane was added 34 μl of isobutyl chloroformate under ice-cooling, followed by stirring at room temperature overnight. The insoluble material was removed by filtration, and then to the filtrate were added 16 mg of sodium borohydride and 210 μl of methanol under ice-cooling, followed by stirring for 30 minutes under ice-cooling. To the reaction mixture were added a saturated aqueous ammonium chloride solution and chloroform to carry out a layer separation operation. The organic layer was dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 21 mg of 8-[(2-fluorobenzyl)oxy]-6-(hydroxymethyl)-N-[(1R)-2-hydroxy-1-phenylethyl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide.

Workup

  1. temperaturecooling
  2. customThe insoluble material was removed by filtration
  3. additionto the filtrate were added 16 mg of sodium borohydride and 210 μl of methanol under ice-
  4. temperaturecooling
  5. stirringby stirring for 30 minutes under ice-
  6. temperaturecooling
  7. additionTo the reaction mixture were added a saturated aqueous ammonium chloride solution and chloroform
  8. customa layer separation operation
  9. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  10. customthe solvent was evaporated under reduced pressure
  11. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-69b27d3efd244c969e16e6c8e4869c4f
Source dataset
uspto-grants-2016_09
Patent number
US09447090B2

Reaction notes

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