1,1-Dichloroethane → 8-(cyclohexylmethoxy)-2-methyl-N-(4-methylpiperidin-4-yl)imidazolo[1,2-a]pyridine-3-carboxamide

HRID 64488Notes

Reaction equation

HRID 64488 reaction equation
C([N:8]1[CH2:13][CH2:12][C:11]([NH:15][C:16]([C:18]2[N:22]3[CH:23]=[CH:24][CH:25]=[C:26]([O:27][CH2:28][CH:29]4[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]4)[C:21]3=[N:20][C:19]=2[CH3:35])=[O:17])([CH3:14])[CH2:10][CH2:9]1)C1C=CC=CC=1.ClC(OC(Cl)C)=O.ClC(Cl)C>>[CH:29]1([CH2:28][O:27][C:26]2[C:21]3[N:22]([C:18]([C:16]([NH:15][C:11]4([CH3:14])[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]4)=[O:17])=[C:19]([CH3:35])[N:20]=3)[CH:23]=[CH:24][CH:25]=2)[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]1

Participants

4

Reactant 3

HCID 63651,1-DichloroethaneHCID 5213051-Chloroethyl chloroformateHCID 86713520N-(1-benzyl-4-methylpiperidin-4-yl)-8-(cyclohexylmethoxy)-2-methylimidazolo[1,2-a]pyridine-3-carboxamide

Product 1

HCID 867135218-(cyclohexylmethoxy)-2-methyl-N-(4-methylpiperidin-4-yl)imidazolo[1,2-a]pyridine-3-carboxamideYield 45.7%

Procedure

A mixture of 1.15 g of N-(1-benzyl-4-methylpiperidin-4-yl)-8-(cyclohexylmethoxy)-2-methylimidazolo[1,2-a]pyridine-3-carboxamide, 0.4 mL of 1-chloroethyl chloroformate, and 15 mL of dichloroethane was heated to reflux overnight. After leaving to be cooled at room temperature, the solvent was evaporated under reduced pressure, and to the residue was added 15 mL of methanol, followed by heating to reflux for 6 hours. After leaving to be cooled at room temperature, the solvent was evaporated under reduced pressure, and to the residue were added a saturated aqueous sodium hydrogen carbonate 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 residue was purified by silica gel column chromatography to obtain 426 mg of 8-(cyclohexylmethoxy)-2-methyl-N-(4-methylpiperidin-4-yl)imidazolo[1,2-a]pyridine-3-carboxamide.

Workup

  1. temperaturewas heated
  2. temperatureto reflux overnight
  3. customAfter leaving
  4. customthe solvent was evaporated under reduced pressure
  5. additionto the residue was added 15 mL of methanol
  6. temperatureby heating
  7. temperatureto reflux for 6 hours
  8. customAfter leaving
  9. temperatureto be cooled at room temperature
  10. customthe solvent was evaporated under reduced pressure
  11. additionto the residue were added a saturated aqueous sodium hydrogen carbonate solution and chloroform
  12. customa layer separation operation
  13. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  14. customthe solvent was evaporated under reduced pressure
  15. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-f001fbad9f2f4502ae91e3cad2098ccc
Source dataset
uspto-grants-2016_09
Patent number
US09447090B2

Reaction notes

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