Water → HCID 57899135, compound

HRID 2401524Notes

Reaction equation

HRID 2401524 reaction equation
[C:1]([O:5][C:6](=[O:29])[NH:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:22]=[CH:21][N:20]=[C:19]3[C:15]=2[N:16]=[CH:17][N:18]3[CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:32]I.O>CN(C)C=O.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:29])[N:7]([CH3:32])[CH:8]1[CH2:9][CH2:10][N:11]([C:14]2[N:22]=[CH:21][N:20]=[C:19]3[C:15]=2[N:16]=[CH:17][N:18]3[CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)[CH2:12][CH2:13]1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 57899141HCID 57899141, compound

Product 1

HCID 57899135HCID 57899135, compoundYield 74.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

The {1-[9-(tetrahydro-pyran-2-yl)-9H-purin-6-yl]-piperidin-4-yl}-carbamic acid tert-butyl ester (107.7 mg, 0.27 mmol) of Example 1A was dissolved in anhydrous dimethylformamide (1 ml) and the solution was cooled to 0° C. in an ice bath. Sodium hydride (13 mg, 60% suspension in oil, 0.33 mmol) was added in small portions. The suspension was stirred vigorously for an additional 20 minutes at 0° C. and then the methyl iodide (0.020 ml, 0.32 mmol) was added drop wise. After stirring the reaction mixture for 30 minutes at 0° C. this was brought to room temperature and left stirring additionally overnight. Water (1.2 ml), followed by ethyl acetate (5 ml) was added to the reaction mixture. The organic layer was separated, washed with water, 0.1M HCl, a saturated aqueous NaHCO3 solution, and brine before being dried and concentrated in vacuo. The crude product was purified by flash silica column chromatography eluting with 5% methanol in dichloromethane to afford the required compound as a white solid (83 mg, 0.2 mmol, 73%) LC-MS (LCT) Rt 7.07 [M+H]+417.

Workup

  1. stirringAfter stirring the reaction mixture for 30 minutes at 0° C.
  2. customthis was brought to room temperature
  3. waitleft
  4. stirringstirring additionally overnight
  5. additionwas added to the reaction mixture
  6. customThe organic layer was separated
  7. washwashed with water, 0.1M HCl
  8. dry with materiala saturated aqueous NaHCO3 solution, and brine before being dried
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by flash silica column chromatography
  11. washeluting with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-0d9d43aac1c54f79bc77ea4e676103d4
Source dataset
uspto-grants-2014_08
Patent number
US08796293B2

Reaction notes

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