Hydrochloric Acid → 8-(cyclohexylmethoxy)-N-[(3S,5S)-5-(hydroxymethyl)-1-methylpyrrolidin-3-yl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide dihydrochloride

HRID 64484Notes

Reaction equation

HRID 64484 reaction equation
[CH:1]1([CH2:7][O:8][C:9]2[C:10]3[N:11]([C:15]([C:19]([NH:21][C@@H:22]4[CH2:26][N:25]([CH3:27])[C@H:24]([C:28](OC)=[O:29])[CH2:23]4)=[O:20])=[C:16]([CH3:18])[N:17]=3)[CH:12]=[CH:13][CH:14]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].C([Al+]CC(C)C)C(C)C.C1(C)C=CC=CC=1.[ClH:49]>ClCCl>[ClH:49].[ClH:49].[CH:1]1([CH2:7][O:8][C:9]2[C:10]3[N:11]([C:15]([C:19]([NH:21][C@H:22]4[CH2:23][C@@H:24]([CH2:28][OH:29])[N:25]([CH3:27])[CH2:26]4)=[O:20])=[C:16]([CH3:18])[N:17]=3)[CH:12]=[CH:13][CH:14]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 86583787Diisobutylaluminumhydride tolueneHCID 86713516methyl (2S,4S)-4-({[8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl]carbonyl}amino)-1-methylpyrrolidine-2-carboxylate

Product 1

HCID 867135148-(cyclohexylmethoxy)-N-[(3S,5S)-5-(hydroxymethyl)-1-methylpyrrolidin-3-yl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide dihydrochloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 150 mg of methyl (2S,4S)-4-({[8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl]carbonyl}amino)-1-methylpyrrolidine-2-carboxylate and 4 ml of dichloromethane was added dropwise 1.5 ml of a 1 M diisobutylaluminum hydride/toluene solution under ice-cooling, followed by stirring for 2 hours under ice-cooling. Subsequently, 1 M hydrochloric acid was added thereto, the reaction mixture was filtered over Celite, and to the filtrate were added ethyl acetate to carry out a layer separation operation. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography. To a solution of the obtained purified product in ethyl acetate was added a hydrogen chloride/ethyl acetate solution, and the resulting solid was collected by filtration and dried to obtain 25 mg of 8-(cyclohexylmethoxy)-N-[(3S,5S)-5-(hydroxymethyl)-1-methylpyrrolidin-3-yl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide dihydrochloride.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. filtrationthe reaction mixture was filtered over Celite
  4. additionto the filtrate were added ethyl acetate
  5. customa layer separation operation
  6. washThe organic layer was washed with water and saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customThe solvent was evaporated under reduced pressure
  9. customthe obtained residue was purified by silica gel column chromatography
  10. customTo a solution of the obtained purified product in ethyl acetate
  11. additionwas added a hydrogen chloride/ethyl acetate solution
  12. filtrationthe resulting solid was collected by filtration
  13. customdried

Sources & evidence

ORD record
ord-afc08e8b14ee4ab58947b6f11a93c99a
Source dataset
uspto-grants-2016_09
Patent number
US09447090B2

Reaction notes

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