Piperidine → HCID 21129804, compound

HRID 1371230Notes

Reaction equation

HRID 1371230 reaction equation
Cl[C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]2[CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[O:11][C:3]=12.[NH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1>CN(C=O)C>[CH3:8][C:6]1[N:5]=[C:4]2[CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[O:11][C:3]2=[C:2]([N:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[CH:7]=1

Participants

4

Reactant 2

HCID 8082PiperidineHCID 21129777HCID 21129777, compound

Product 1

HCID 21129804HCID 21129804, compoundYield 68.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of 7-chloro-5-methyl-2-phenylfurano[3,2-b]pyridine (Example 228 (c)) (365 mg, 1.50 mmol) and piperidine (5 mL, 50.5 mmol) was added DMF (2 mL). Mixture stirred at 120° C. under N2 for 26 h. After cooling, the reaction mixture was concentrated. The residue was diluted with H2O (70 mL) and Et2O (50 mL). The mixture was transferred to a separatory funnel and the organic solution was collected. The aqueous solution was washed with Et2O (2×40 mL). The organic solutions were combined, washed with H2O (50 mL), saturated NaCl (70 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel with 50:50 EtOAc:hexanes as elutant to give 300 mg (68%) of 5-methyl-2-phenyl-7-piperidylfurano[3,2-b]pyridine as a cream colored solid. This material (298 mg, 1.02 mmol) was dissolved in EtOAc (20 mL) and heated to boiling. To the hot solution was added 1M etheral HCl (1.00 mL, 1.00 mmol). The solution was left to cool to 25° C. The resulting solid was collected by filtration, washed with EtOAc (2×5 mL), Et2O (3×5 mL) and dried under vacuum at 25° C. to give 290 mg (59%) of the title compound as a white colored powder. Mp: >280° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.67 (br s, 6), 2.49 (s, 3), 3.94 (br s, 4), 6.93 (s, 1), 7.46-7.54 (m, 4), 7.98 (dd, 2, J=1.5, 7.6), 14.14 (s, 1). MS m/z: 293 (M+1 for free base). Anal. Calcd for C19H20N2O.HCl.0.25H2O: C, 68.46; H, 6.50; N, 8.41; Cl, 10.64. Found C, 68.60; H, 6.44; N, 8.43; Cl, 10.56.

Workup

  1. temperatureAfter cooling
  2. concentrationthe reaction mixture was concentrated
  3. additionThe residue was diluted with H2O (70 mL) and Et2O (50 mL)
  4. customThe mixture was transferred to a separatory funnel
  5. customthe organic solution was collected
  6. washThe aqueous solution was washed with Et2O (2×40 mL)
  7. washwashed with H2O (50 mL), saturated NaCl (70 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by flash chromatography on silica gel with 50:50 EtOAc

Sources & evidence

ORD record
ord-88302f9eb7714e67a42b965341a7dcc7
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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