Dimethylformamide → 3-(7-Hydroxy-2,4-dimethoxy-5,5-dimethyl-5,7-dihydro-furo[3,4-d]pyrimidin-7-yl)-5-methyl-benzonitrile

HRID 426283Notes

Reaction equation

HRID 426283 reaction equation
[C:1]([CH2:3][C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([CH3:12])[CH:11]=1)[C:7]#[N:8])#[N:2].ClC1[C:19]([C:20]([OH:23])([CH3:22])[CH3:21])=[C:18]([O:24][CH3:25])[N:17]=[C:16]([O:26][CH3:27])N=1.[H-].[Na+].CN(C=[O:34])C>>[OH:34][C:3]1([C:4]2[CH:5]=[C:6]([CH:9]=[C:10]([CH3:12])[CH:11]=2)[C:7]#[N:8])[C:1]2[N:2]=[C:16]([O:26][CH3:27])[N:17]=[C:18]([O:24][CH3:25])[C:19]=2[C:20]([CH3:22])([CH3:21])[O:23]1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 237307032-(4-Chloro-2,6-dimethoxy-pyrimidin-5-yl)-propan-2-olHCID 667054463-(Cyanomethyl)-5-methylbenzonitrile

Product 1

HCID 591846603-(7-Hydroxy-2,4-dimethoxy-5,5-dimethyl-5,7-dihydro-furo[3,4-d]pyrimidin-7-yl)-5-methyl-benzonitrileYield 18%

Conditions

Temperature
0 °C

Procedure

3-Cyanomethyl-5-methyl-benzonitrile (0.067 g, 0.432 mmol) and 2-(4-Chloro-2,6-dimethoxy-pyrimidin-5-yl)-propan-2-ol (0.100 g, 0.432 mmol) was dissolved in DMF (1.5 mL) and cooled to 0° C. 60% Sodium hydride (0.035 g, 0.64 mmol) was added portionwise and the reaction was stirred at 0° C. for 1 h, then rt overnight. The reaction was quenched with 1N HCl, extracted with ethyl acetate and washed with saturated ammonium chloride solution. Organic layer was dried (MgSO4) and concentrated and purified by flash column chromatography (silica gel, 0 to 40% ethyl acetate/hexane) to give a white solid (0.027 g, 18%). 1H NMR (300 MHz, CDCl3): δ 7.80 (s, 2H), 7.39 (s, 1H), 4.01 (s, 3H), 3.93 (s, 3H), 2.37 (s, 3H), 1.66 (s, 3H), 1.63 (s, 3H). Mass spectrum: 342.3 (M+H)+.

Workup

  1. customrt overnight
  2. customThe reaction was quenched with 1N HCl
  3. extractionextracted with ethyl acetate
  4. washwashed with saturated ammonium chloride solution
  5. dry with materialOrganic layer was dried (MgSO4)
  6. concentrationconcentrated
  7. custompurified by flash column chromatography (silica gel, 0 to 40% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-b167f60d3dbd4584b4886a3d9f0e1443
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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