Boron trifluoride → 2-{4-[(1-Cyclobutylpiperidin-4-yl)oxy]phenyl}-3-methyl-3,7-dihydropyrido[3,4-d]pyrimidine-4,8-dione

HRID 2422634Notes

Reaction equation

HRID 2422634 reaction equation
[CH:1]1([N:5]2[CH2:10][CH2:9][CH:8]([O:11][C:12]3[CH:17]=[CH:16][C:15]([C:18]4[N:19]([CH3:31])[C:20](=[O:30])[C:21]5[CH:27]=[CH:26][N:25]=[C:24]([O:28]C)[C:22]=5[N:23]=4)=[CH:14][CH:13]=3)[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.B(F)(F)F.[OH-].[Na+]>ClCCl.C(OCC)(=O)C>[CH:1]1([N:5]2[CH2:6][CH2:7][CH:8]([O:11][C:12]3[CH:17]=[CH:16][C:15]([C:18]4[N:19]([CH3:31])[C:20](=[O:30])[C:21]5[CH:27]=[CH:26][NH:25][C:24](=[O:28])[C:22]=5[N:23]=4)=[CH:14][CH:13]=3)[CH2:9][CH2:10]2)[CH2:2][CH2:3][CH2:4]1

Participants

6

Reactant 3

HCID 6356Boron trifluorideHCID 14798Sodium HydroxideHCID 11539020Pyrido[3,4-d]pyrimidin-4(3H)-one, 2-[4-[(1-cyclobutyl-4-piperidinyl)oxy]phenyl]-8-methoxy-3-methyl-

Product 1

HCID 672438532-{4-[(1-Cyclobutylpiperidin-4-yl)oxy]phenyl}-3-methyl-3,7-dihydropyrido[3,4-d]pyrimidine-4,8-dioneYield 62%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

2-{4-[(1-Cyclobutylpiperidin-4-yl)oxy]phenyl}-8-methoxy-3-methylpyrido[3,4-d]pyrimidin-4(3H)-one (500 mg, 1.19 mmol) was dissolved in dichloromethane (1 ml), and with stirring at 0° C., boron trifluoride (1.0 M in CH2Cl2, 3.9 mL) was added thereto, then gradually heated up to room temperature, and stirred at that temperature for 20 hours. The reaction solution was diluted with ethyl acetate, and with cooling with ice, this was poured into aqueous 1 N sodium hydroxide solution, and extracted with ethyl acetate. The organic layer was washed with saturated saline water, and dried with magnesium sulfate. The solvent was evaporated off, and the residue was purified through silica gel column chromatography (chloroform/methanol=1/0 to 9/1 and its polarity was stepwise increased up to 5/1) to obtain the intended compound (300 mg, 62%) as a pale yellow solid.

Workup

  1. temperaturegradually heated up to room temperature
  2. stirringstirred at that temperature for 20 hours
  3. temperaturewith cooling with ice
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with saturated saline water
  6. dry with materialdried with magnesium sulfate
  7. customThe solvent was evaporated off
  8. customthe residue was purified through silica gel column chromatography (chloroform/methanol=1/0 to 9/1 and its polarity
  9. temperaturewas stepwise increased up to 5/1)

Sources & evidence

ORD record
ord-0e150db00faf487f95cbdace8eda4402
Source dataset
uspto-grants-2011_06
Patent number
US07960394B2

Reaction notes

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