Water → N-[(3S)-1-carbamoylpiperidin-3-yl]-8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridine-3-carboxamide hydrochloride

HRID 64467Notes

Reaction equation

HRID 64467 reaction equation
[ClH:1].Cl.[CH:3]1([CH2:9][O:10][C:11]2[C:12]3[N:13]([C:17]([C:21]([NH:23][C@H:24]4[CH2:29][CH2:28][CH2:27][NH:26][CH2:25]4)=[O:22])=[C:18]([CH3:20])[N:19]=3)[CH:14]=[CH:15][CH:16]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(N(CC)CC)C.C[Si]([N:41]=[C:42]=[O:43])(C)C.O>C(O)(C)C.C(OCC)(=O)C>[ClH:1].[C:42]([N:26]1[CH2:27][CH2:28][CH2:29][C@H:24]([NH:23][C:21]([C:17]2[N:13]3[CH:14]=[CH:15][CH:16]=[C:11]([O:10][CH2:9][CH:3]4[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]4)[C:12]3=[N:19][C:18]=2[CH3:20])=[O:22])[CH2:25]1)(=[O:43])[NH2:41]

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 70696Trimethylsilyl isocyanateHCID 867134908-(cyclohexylmethoxy)-2-methyl-N-[(3S)-piperidin-3-yl]imidazo[1,2-a]pyridine-3-carboxamide dihydrochloride

Product 1

HCID 86713488N-[(3S)-1-carbamoylpiperidin-3-yl]-8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridine-3-carboxamide hydrochloride

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 200 mg of 8-(cyclohexylmethoxy)-2-methyl-N-[(3S)-piperidin-3-yl]imidazo[1,2-a]pyridine-3-carboxamide dihydrochloride in 5 ml of isopropylalcohol were added 220 μl of triethylamine and 72 μl of (trimethylsilyl)isocyanate, followed by stirring for 6 hours. To the reaction mixture were added water and ethyl acetate to carry out a layer separation operation. The organic layer was washed with water, a saturated aqueous sodium hydrogen carbonate solution, and saturated brine in this order, and dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography. The obtained solid was suspended in ethyl acetate, and 120 μl of 4 M hydrogen chloride/ethyl acetate solution was added thereto, followed by stirring. The resulting solid was collected by filtration and dried to obtain 170 mg of N-[(3S)-1-carbamoylpiperidin-3-yl]-8-(cyclohexylmethoxy)-2-methylimidazo[1,2-a]pyridine-3-carboxamide hydrochloride.

Workup

  1. customa layer separation operation
  2. washThe organic layer was washed with water
  3. dry with materiala saturated aqueous sodium hydrogen carbonate solution, and saturated brine in this order, and dried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customthe obtained residue was purified by silica gel column chromatography
  6. addition120 μl of 4 M hydrogen chloride/ethyl acetate solution was added
  7. stirringby stirring
  8. filtrationThe resulting solid was collected by filtration
  9. customdried

Sources & evidence

ORD record
ord-7d34e09323c04c6aaa3a4a88734ec337
Source dataset
uspto-grants-2016_09
Patent number
US09447090B2

Reaction notes

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