Hydrochloric Acid → methyl {(3S)-1-[5-(adamantan-1-ylcarbamoyl)-6-(propylthio)pyridin-2-yl]piperidin-3-yl}acetate

HRID 1187377Notes

Reaction equation

HRID 1187377 reaction equation
[C:1]12([NH:11][C:12](=[O:24])[C:13]3[CH:18]=[CH:17][C:16](Cl)=[N:15][C:14]=3[S:20][CH2:21][CH2:22][CH3:23])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[NH:25]1[CH2:30][CH2:29][CH2:28][C@@H:27]([CH2:31][C:32]([O:34][CH3:35])=[O:33])[CH2:26]1.Cl.C(=O)([O-])[O-].[K+].[K+]>C(#N)CCC.CCOC(C)=O>[C:1]12([NH:11][C:12]([C:13]3[CH:18]=[CH:17][C:16]([N:25]4[CH2:30][CH2:29][CH2:28][C@@H:27]([CH2:31][C:32]([O:34][CH3:35])=[O:33])[CH2:26]4)=[N:15][C:14]=3[S:20][CH2:21][CH2:22][CH3:23])=[O:24])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 40153895methyl 2-[(3S)-piperidin-3-yl]acetateHCID 59830706N-adamantan-1-yl-6-chloro-2-(propylthio)nicotinamide

Product 1

HCID 59830770methyl {(3S)-1-[5-(adamantan-1-ylcarbamoyl)-6-(propylthio)pyridin-2-yl]piperidin-3-yl}acetateYield 44%

Reagents, catalysts & solvents 2

HCID 8008ButyronitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-adamantan-1-yl-6-chloro-2-(propylthio)nicotinamide (0.365 g, 1 mmol) was added to (S)-methyl 2-(piperidin-3-yl)acetate.HCl (0.194 g, 1 mmol) and potassium carbonate (0.415 g, 3 mmol) in butyronitrile (4 mL) was heated at 150° C. for 2 hours. The reaction mixture was diluted with EtOAc (50 mL), and washed sequentially with water (20 mL) and brine (20 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in hexane. Pure fractions were evaporated to dryness to afford methyl {(3S)-1-[5-(adamantan-1-ylcarbamoyl)-6-(propylthio)pyridin-2-yl]piperidin-3-yl}acetate (0.215 g, 44%) as a white solid.

Workup

  1. washwashed sequentially with water (20 mL) and brine (20 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customto afford crude product
  6. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in hexane
  7. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-7174c585e1974e7684df259981f3383f
Source dataset
uspto-grants-2014_03
Patent number
US08673938B2

Reaction notes

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