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

HRID 1752268Notes

Reaction equation

HRID 1752268 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]=[C:32]([CH3:34])[S:31][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]=[C:32]([CH3:34])[S:31][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 64916832-(Chloromethyl)-6-methylthieno[2,3-d]pyrimidin-4(3H)-oneHCID 712122103-(4-(4-Methoxybenzoyl)piperidin-1-yl)pyrrolidin-2-one

Product 1

HCID 712122132-{3-[4-(4-Methoxy-benzoyl)-piperidin-1-yl]-2-oxo-pyrrolidin-1-ylmethyl}-6-methyl-4a,7a-dihydro-3H-thieno[2,3-d]pyrimidin-4-oneYield 95.4%

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 2-chloromethyl-6-methyl-3H-thieno[2,3-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 (70.5 mg, 95.4% yield). HRMS calculated for C25H28N4O4S 480.5903. found (ESI, [M+H]+) 481.1907. 1H NMR (400 MHz, MeOD) δ ppm 1.66-1.93 (m, 4H) 2.05-2.30 (m, 2H) 2.51-2.63 (m, 1H) 2.79-2.90 (m, 1H) 2.90-2.98 (m, 1H) 3.03-3.18 (m, 1H) 3.33-3.54 (m, 4H) 3.65-3.75 (m, 1H) 3.87 (s, 3H) 4.20-4.31 (m, 1H) 4.51-4.62 (m, 1H) 6.94-7.06 (m, 3H) 7.98 (d, J=9.03 Hz, 2H), analytical RP-HPLC retention time=3.22 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-3c663871a7c24b0291a60a9bb14d4a7d
Source dataset
uspto-grants-2015_10
Patent number
US09163003B2

Reaction notes

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