4-(Chloromethyl)pyrimidine → 2-(Pyrimidin-4-ylmethyl)isoindoline-1,3-dione

HRID 2067331Notes

Reaction equation

HRID 2067331 reaction equation
Cl[CH2:2][C:3]1[CH:8]=[CH:7][N:6]=[CH:5][N:4]=1.[C:9]1(=[O:19])[NH:13][C:12](=[O:14])[C:11]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:10]12.[K]>CN(C)C=O>[N:6]1[CH:7]=[CH:8][C:3]([CH2:2][N:13]2[C:9](=[O:19])[C:10]3[C:11](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:12]2=[O:14])=[N:4][CH:5]=1

Participants

4

Reactant 2

HCID 131235534-(Chloromethyl)pyrimidineHCID 24194345Phthalimide potassium salt

Product 1

HCID 666302422-(Pyrimidin-4-ylmethyl)isoindoline-1,3-dioneYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-(chloromethyl)pyrimidine (4.10 g, 31.9 mmol, prepared according to R. W. Carling et al., J. Med. Chem., (2004), Vol. 47, pp. 1807-1822) and potassium phthalimide (5.91 g, 31.89 mmol) in N,N-dimethylformamide (60 mL) was heated to 110° C. for 16 hours. The reaction mixture was cooled to ambient temperature, and concentrated in vacuo. The residue was dissolved in dichloromethane (100 mL), washed with water (50 mL) and brine (50 ml). The organic layer was dried over anhydrous sodium sulphate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with 40-50% ethyl acetate in hexanes to afford 2-(pyrimidin-4-ylmethyl)isoindoline-1,3-dione in 40% yield (3.0 g): 1H NMR (300 MHz, CDCl3) δ 9.13 (s, 1H), 8.70 (br s, 1H), 7.93-7.86 (m, 2H), 7.79-7.75 (m, 2H), 7.30 (d, J=6.0 Hz, 1H), 4.99 (s, 2H); MS (ES+) m/z 240.1 (M+1).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in dichloromethane (100 mL)
  3. washwashed with water (50 mL) and brine (50 ml)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography
  8. washeluted with 40-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-4091917eae29412dac28348f75185b01
Source dataset
uspto-grants-2012_10
Patent number
US08293768B2

Reaction notes

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