Sodium hydride → 3-[Cyano-(3-ethyl-5-isopropyl-1-methoxymethyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yl)-methyl]-5-methyl-benzonitrile

HRID 2194763Notes

Reaction equation

HRID 2194763 reaction equation
Cl[C:2]1[N:7]([CH2:8][CH3:9])[C:6](=[O:10])[N:5]([CH2:11][O:12][CH3:13])[C:4](=[O:14])[C:3]=1[CH:15]([CH3:17])[CH3:16].[C:18]([C:20]1[CH:21]=[C:22]([CH:26]=[C:27]([CH3:29])[CH:28]=1)[CH2:23][C:24]#[N:25])#[N:19].[H-].[Na+].[Cl-].[NH4+]>CN(C=O)C>[C:24]([CH:23]([C:2]1[N:7]([CH2:8][CH3:9])[C:6](=[O:10])[N:5]([CH2:11][O:12][CH3:13])[C:4](=[O:14])[C:3]=1[CH:15]([CH3:17])[CH3:16])[C:22]1[CH:21]=[C:20]([CH:28]=[C:27]([CH3:29])[CH:26]=1)[C:18]#[N:19])#[N:25]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 582035516-chloro-1-ethyl-5-isopropyl-3-methoxymethyl-1H-pyrimidine-2,4-dioneHCID 667054463-(Cyanomethyl)-5-methylbenzonitrile

Product 1

HCID 252149573-[Cyano-(3-ethyl-5-isopropyl-1-methoxymethyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yl)-methyl]-5-methyl-benzonitrileYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 6-chloro-1-ethyl-5-isopropyl-3-methoxymethyl-1H-pyrimidine-2,4-dione (1.43 g, 5.48 mmol) and 3-cyano-5-methylbenzyl cyanide (857 mg, 5.48 mmol) in DMF (12 mL) in a water bath, was added 60% NaH (483 mg, 12 mmol). After 15 min., the mixture was stirred at room temperature for overnight. Excess ammonium chloride was added to the mixture and stirring was continued for 1 hr. The mixture was then evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, ethyl acetate:hexane (from 1:4 to 2:3)) to give 1.6 g (80%) of 3-[cyano-(3-ethyl-5-isopropyl-1-methoxymethyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yl)-methyl]-5-methyl-benzonitrile as a yellow solid. m.p. 202-205° C.; 1H-NMR (200 MHz, DMSO-d6) δ 0.77 (3H, d, J=6.8 Hz), 1.10 (3H, t, J=6.8 Hz), 1.20 (3H, d, J=6.8 Hz), 2.40 (3H, s), 2.55 (1H, m), 3.71 (1H, m), 4.05 (1H, m), 5.21 (2H, dd, J=11.2 Hz, J=9.4 Hz), 6.26 (1H, s), 7.60 (1H, s), 7.69 (1H, s), 7.73 (1H, s); m/z (EI) 380 (M+).

Workup

  1. stirringstirring
  2. waitwas continued for 1 hr
  3. customThe mixture was then evaporated in vacuo
  4. customthe residue was purified by silica gel column chromatography (eluent, ethyl acetate:hexane (from 1:4 to 2:3))

Sources & evidence

ORD record
ord-43cb5952034c41ad94f07880244264c1
Source dataset
uspto-grants-2012_12
Patent number
US08334295B2

Reaction notes

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