Sodium hydride → 6-{3-[4-(4-Methoxy-benzoyl)-piperidin-1-yl]-2-oxo-pyrrolidin-1-ylmethyl}-1-methyl-1,3a,5,7a-tetrahydro-pyrazolo[3,4-d]pyrimidin-4-one

HRID 1752266Notes

Reaction equation

HRID 1752266 reaction equation
[CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([CH:15]3[CH2:19][CH2:18][NH:17][C:16]3=[O:20])[CH2:11][CH2:10]2)=[O:8])=[CH:5][CH:4]=1.Cl[CH2:24][C:25]1[NH:26][C:27](=[O:35])[C:28]2[CH:33]=[N:32][N:31]([CH3:34])[C:29]=2[N:30]=1.[H-].[Na+]>C1COCC1.CCOCC>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([CH:15]3[CH2:19][CH2:18][N:17]([CH2:24][C:25]4[NH:26][C:27](=[O:35])[CH:28]5[CH:33]=[N:32][N:31]([CH3:34])[CH:29]5[N:30]=4)[C:16]3=[O:20])[CH2:11][CH2:10]2)=[O:8])=[CH:21][CH:22]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 712122103-(4-(4-Methoxybenzoyl)piperidin-1-yl)pyrrolidin-2-oneHCID 1357831546-(chloromethyl)-1-methyl-1H,4H,5H-pyrazolo(3,4-d)pyrimidin-4-one

Product 1

HCID 712121496-{3-[4-(4-Methoxy-benzoyl)-piperidin-1-yl]-2-oxo-pyrrolidin-1-ylmethyl}-1-methyl-1,3a,5,7a-tetrahydro-pyrazolo[3,4-d]pyrimidin-4-oneYield 87%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 3-[4-(4-methoxy-benzoyl)-piperidin-1-yl]-pyrrolidin-2-one (0.165 mmol, 50 mg) and 6-chloromethyl-1-methyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one (0.165 mmol, 33 mg) in THF (2 mL) was added sodium hydride (60%, 0.331 mmol, 23 mg) and heated to 70° C. for 1 hour. The reaction was allowed to cool to ambient temperature, diluted with 10 mL of ether, and the resulting solid in suspension was filtered and dried under vacuum provided the title compound as an off-white solid (66.4 mg, 87% yield). HRMS calculated for C24H28N6O4 464.5286. found (ESI, [M+H]+) 465.2256. 1H NMR (400 MHz, MeOD) δ ppm 1.70-1.93 (m, 4H) 2.09-2.31 (m, 2H) 2.53-2.66 (m, 1H) 2.80-2.91 (m, 1H) 2.93-3.02 (m, 1H) 3.10-3.21 (m, 1H) 3.33-3.43 (m, 2H) 3.48-3.57 (m, 2H) 3.65-3.75 (m, 1H) 3.83-3.90 (m, 6H) 4.37-4.51 (m, 2H) 6.97 (d, J=9.03 Hz, 2H) 7.83-7.91 (m, 1H) 7.97 (d, J=9.03 Hz, 2H), analytical RP-HPLC retention time=2.77 min

Workup

  1. temperatureto cool to ambient temperature
  2. filtrationthe resulting solid in suspension was filtered
  3. customdried under vacuum

Sources & evidence

ORD record
ord-c94ce8c91daf47249c87e65ea4db8184
Source dataset
uspto-grants-2015_10
Patent number
US09163003B2

Reaction notes

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