Sodium hydride → 2-[4-(4-Methoxy-benzoyl)-2'-oxo-[1,3']bipiperidinyl-1'-ylmethyl]-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one

HRID 1752271Notes

Reaction equation

HRID 1752271 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:25]=[CH:24][C:8]([C:9]([CH:11]2[CH2:16][CH2:15][N:14]([CH:17]3[CH2:22][CH2:21][CH2:20][NH:19][C:18]3=[O:23])[CH2:13][CH2:12]2)=[O:10])=[CH:7][CH:6]=1.Cl[CH2:27][C:28]1[NH:29][C:30](=[O:38])[C:31]2[CH2:37][O:36][CH2:35][CH2:34][C:32]=2[N:33]=1>C1COCC1>[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([C:9]([CH:11]2[CH2:16][CH2:15][N:14]([CH:17]3[CH2:22][CH2:21][CH2:20][N:19]([CH2:27][C:28]4[NH:29][C:30](=[O:38])[C:31]5[CH2:37][O:36][CH2:35][CH2:34][C:32]=5[N:33]=4)[C:18]3=[O:23])[CH2:13][CH2:12]2)=[O:10])=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 712122074-(4-Methoxybenzoyl)[1,3'-bipiperidin]-2'-oneHCID 1357419472-(Chloromethyl)-7,8-dihydro-3H-pyrano[4,3-D]pyrimidin-4(5H)-one

Product 1

HCID 1362327282-[4-(4-Methoxy-benzoyl)-2'-oxo-[1,3']bipiperidinyl-1'-ylmethyl]-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-oneYield 31.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred solution of NaH (23.8 mg, 0.942 mmol, 2.1 eq) in THF (10 mL) were added 4-(4-methoxy-benzoyl)-[1,3′]bipiperidinyl-2′-one (142 mg, 0.449 mmol, 1.0 eq) and 2-chloromethyl-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one (90 mg, 0.449 mmol, 1.0 eq). The reaction was let to stir at 70° C. for 3 h. The solid precipitate was filtered off and washed with CH2Cl2. The solvent of the mother liquor was evaporated and the residue purified by flash chromatography on silica gel (0-15% MeOH/CH2Cl2) to afford the title compound as an off-white powder (60 mg, 0.139 mmol, 31.1% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.34 (br s, 1H) 7.94 (d, J=8.59 Hz, 2H) 7.03 (d, J=8.59 Hz, 2H) 4.14-4.54 (m, 5H) 4.06-4.10 (m, 1H) 3.45 (br s, 1H) 3.18 (d, J=5.05 Hz, 3H) 3.03 (br s, 1H) 2.85 (br s, 2H) 2.30-2.65 (m, 5H) 1.30-2.05 (m, 9H). HR-MS (m/z, MH+): 481.2461, 482.2471. HPLC retention time: 2.78 min (Agilent column 3.0×100 mm 3 um C18 column; flow rate of 1.0 mL/min with gradient from 5% to 95% acetonitrile in 10 min, 0.1% FA)

Workup

  1. filtrationThe solid precipitate was filtered off
  2. washwashed with CH2Cl2
  3. customThe solvent of the mother liquor was evaporated
  4. customthe residue purified by flash chromatography on silica gel (0-15% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-430e5fb9c091403bb30815b8ba239de9
Source dataset
uspto-grants-2015_10
Patent number
US09163003B2

Reaction notes

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