Sodium hydride → 2-{3-[4-(4-Methoxy-benzoyl)-piperidin-1-yl]-2-oxo-pyrrolidin-1-ylmethyl}-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one

HRID 1752262Notes

Reaction equation

HRID 1752262 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[CH2:34][O:33][CH2:32][CH2:31][C:29]=2[N:30]=1.[H-].[Na+]>C1COCC1.CN(C=O)C.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])[C:28]5[CH2:34][O:33][CH2:32][CH2:31][C:29]=5[N:30]=4)[C:16]3=[O:20])[CH2:11][CH2:10]2)=[O:8])=[CH:21][CH:22]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 712122103-(4-(4-Methoxybenzoyl)piperidin-1-yl)pyrrolidin-2-oneHCID 1357419472-(Chloromethyl)-7,8-dihydro-3H-pyrano[4,3-D]pyrimidin-4(5H)-one

Product 1

HCID 1362327162-{3-[4-(4-Methoxy-benzoyl)-piperidin-1-yl]-2-oxo-pyrrolidin-1-ylmethyl}-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-oneYield 107.9%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 3-[4-(4-methoxy-benzoyl)-piperidin-1-yl]-pyrrolidin-2-one (43.7 mmol, 13.2 g) and 2-chloromethyl-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one (48 mmol, 9.6 g) in THF (400 mL) and DMF formula (20 mL) was added sodium hydride (60%, 153 mmol, 6.1 g) and heated to 70° C. for 1 hour. The reaction was allowed to cool to ambient temperature, diluted with 1 L of ether, and the resulting solid in suspension was filtered and dried under vacuum provided the title compound as an off-white solid (22 g, 95.3% yield). HRMS calculated for C25H30N4O5 466.5417. found (ESI, [M+H]+) 467.2305. 1H NMR (400 MHz, MeOD) δ ppm 1.67-1.92 (m, 4H) 2.05-2.24 (m, 2H) 2.47-2.64 (m, 3H) 2.72-2.82 (m, 1H) 2.84-2.93 (m, 1H) 3.06-3.15 (m, 1H) 3.26-3.47 (m, 10H) 3.68 (t, J=8.78 Hz, 1H) 3.83-3.99 (m, 5H) 4.16 (d, J=15.56 Hz, 1H) 4.40-4.58 (m, 3H) 7.01 (d, J=9.03 Hz, 2H) 7.97 (d, J=9.03 Hz, 2H), analytical RP-HPLC (Novapak 150×3.9 mm C18 column: mobile phase: 10-90% acetonitrile/water with 0.1% TFA, at 2 mL/min over 5 min.) retention time=2.455 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-0e4f510f16554052a241081847695308
Source dataset
uspto-grants-2015_10
Patent number
US09163003B2

Reaction notes

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