Reaktion #92760

Reaktionsgleichung

8-(cyclohexylmethoxy)-2-methyl-N-[(3S)-piperidin-3-yl]imidazo[1,2-a]pyridine-3-carboxamide dihydrochloride

triethylamine

[(1-ethoxy cyclopropyl)oxy](trimethyl)silane

sodium cyanoborohydride

→

8-(cyclohexylmethoxy)-N-[(3S)-1-cyclopropylpiperidin-3-yl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide dihydrochloride

Lösungsmittel

methanol

acetic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturcooling
2. 2
   Temperaturunder heating to reflux
3. 3
   SonstigeThe insoluble material was removed by filtration
4. 4
   Einengenthe filtrate was concentrated under reduced pressure
5. 5
   workup.ADDITIONTo the obtained residue were added saturated aqueous sodium bicarbonate and chloroform
6. 6
   Sonstigea layer separation operation
7. 7
   TrocknenThe organic layer was dried over anhydrous sodium sulfate
8. 8
   Sonstigethe solvent was evaporated under reduced pressure
9. 9
   Sonstigethe obtained residue was purified by silica gel column chromatography
10. 10
    workup.ADDITIONTo a mixture of the obtained
11. 11
    Sonstigepurified product, ethyl acetate, and methanol
12. 12
    workup.ADDITIONwas added a 4 M hydrogen chloride/ethyl acetate solution under ice-
13. 13
    Temperaturcooling
14. 14
    Sonstigethe solvent was evaporated under reduced pressure
15. 15
    workup.ADDITIONTo the obtained residue was added ethyl acetate and hexane
16. 16
    workup.STIRRINGby stirring
17. 17
    FiltrationThe resulting solid was collected by filtration
18. 18
    Sonstigedried

Vorschrift

To a solution of 250 mg of 8-(cyclohexylmethoxy)-2-methyl-N-[(3S)-piperidin-3-yl]imidazo[1,2-a]pyridine-3-carboxamide dihydrochloride in 10 ml of methanol were added 157 μl of triethylamine, 300 mg of Molecular Sieves 3A, 323 μl of acetic acid, 1.53 ml of [(1-ethoxy cyclopropyl)oxy](trimethyl)silane, and 146 mg of sodium cyanoborohydride under ice-cooling, followed by stirring for 6 hours under heating to reflux. The insoluble material was removed by filtration and the filtrate was concentrated under reduced pressure. To the obtained residue were added saturated aqueous sodium bicarbonate and chloroform to carry out a layer separation operation. The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography. To a mixture of the obtained purified product, ethyl acetate, and methanol was added a 4 M hydrogen chloride/ethyl acetate solution under ice-cooling, and the solvent was evaporated under reduced pressure. To the obtained residue was added ethyl acetate and hexane, followed by stirring. The resulting solid was collected by filtration and dried to obtain 136 mg of 8-(cyclohexylmethoxy)-N-[(3S)-1-cyclopropylpiperidin-3-yl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide dihydrochloride.

Quelle