Hydrochloric Acid → methyl [(3S)-1-{5-[methyl(tetrahydro-2H-pyran-4-yl)carbamoyl]-6-(propylthio)pyridin-2-yl}piperidin-3-yl]acetate

HRID 2424921Notes

Reaction equation

HRID 2424921 reaction equation
Cl[C:2]1[CH:17]=[CH:16][C:5]([C:6]([N:8]([CH3:15])[CH:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[O:7])=[C:4]([S:18][CH2:19][CH2:20][CH3:21])[N:3]=1.[NH:22]1[CH2:27][CH2:26][CH2:25][C@@H:24]([CH2:28][C:29]([O:31][CH3:32])=[O:30])[CH2:23]1.Cl.C(=O)([O-])[O-].[K+].[K+]>C(#N)CCC.C(Cl)Cl>[CH3:15][N:8]([CH:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)[C:6]([C:5]1[CH:16]=[CH:17][C:2]([N:22]2[CH2:27][CH2:26][CH2:25][C@@H:24]([CH2:28][C:29]([O:31][CH3:32])=[O:30])[CH2:23]2)=[N:3][C:4]=1[S:18][CH2:19][CH2:20][CH3:21])=[O:7]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 40153895methyl 2-[(3S)-piperidin-3-yl]acetateHCID 580008806-chloro-N-methyl-2-(propylthio)-N-(tetrahydro-2H-pyran-4-yl)nicotinamide

Product 1

HCID 59830659methyl [(3S)-1-{5-[methyl(tetrahydro-2H-pyran-4-yl)carbamoyl]-6-(propylthio)pyridin-2-yl}piperidin-3-yl]acetateYield 57%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8008ButyronitrileSolvent

Procedure

6-chloro-N-methyl-2-(propylthio)-N-(tetrahydro-2H-pyran-4-yl)nicotinamide (0.398 g, 1.21 mmol) was added to (S)-methyl 2-(piperidin-3-yl)acetate.HCl (0.353 g, 1.82 mmol) and potassium carbonate (0.753 g, 5.45 mmol) in butyronitrile (3 mL) was heated at 150° C. for 4 hours. The reaction mixture was diluted with DCM (60 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 100% EtOAc in DCM. Pure fractions were evaporated to dryness to afford methyl [(3S)-1-{5-[methyl(tetrahydro-2H-pyran-4-yl)carbamoyl]-6-(propylthio)pyridin-2-yl}piperidin-3-yl]acetate (0.310 g, 57%) 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 100% EtOAc in DCM
  7. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-3a03f73a3d234a7b85bf66b988362fda
Source dataset
uspto-grants-2011_06
Patent number
US07964618B2

Reaction notes

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