Methanol → 5-[2-(methylamino)ethoxy]quinazolin-4(3H)-one

HRID 1864355Notes

Reaction equation

HRID 1864355 reaction equation
[H-].[Na+].[CH3:3][NH:4][CH2:5][CH2:6][OH:7].F[C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[C:11](=[O:19])[NH:12][CH:13]=[N:14]2.CO>CC(N(C)C)=O>[CH3:3][NH:4][CH2:5][CH2:6][O:7][C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[C:11](=[O:19])[NH:12][CH:13]=[N:14]2

Participants

6

Reactant 4

HCID 887MethanolHCID 80162-(Methylamino)ethanolHCID 24758Sodium hydrideHCID 1354959305-Fluoroquinazolin-4-ol

Product 1

HCID 1363882975-[2-(methylamino)ethoxy]quinazolin-4(3H)-one

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

Sodium hydride (60% dispersion in mineral oil, 732 mg, 18.3 mmol) was suspended in DMA (50 ml) and N-methylethanolamine (734 μl, 9.15 mmol) was added under an atmosphere of nitrogen. The mixture was stirred for 30 minutes at ambient temperature, and 5-fluoroquinazolin-4(3H)-one (1.0 g, 6.10 mmol) was added. The mixture was heated under an atmosphere of nitrogen at 85° C. for 90 minutes. The mixture was cooled to ambient temperature, and the resulting slurry poured into methanol (100 ml). Dowex resin (50WX4-400, 25 g) was added, and the mixture stirred for 1 hour at ambient temperature. The resin was collected by filtration, and washed with methanol (100 ml). The resin was suspended in a solution of ammonia in methanol (2.3 N, 150 ml), and the mixture stirred for 30 minutes. The mixture was filtered and the residue washed with ammonia in methanol (2.3 N, 100 ml). The combined filtrates were concentrated in vacuo, and dried in vacuo (1 mbar, 60° C.) for 16 hours to give 5-[2-(methylamino)ethoxy]quinazolin-4(3H)-one as an off white solid (1.09 g, 82%); NMR Spectrum (DMSO-d6, 400) 2.36 (s, 3H), 2.85 (t, 2H), 5.11 (t, 2H), 6.97 (d, 1H), 7.14 (d, 1H), 7.61 (dd, 1H), 7.97 (s, 1H); Mass spectrum MH+ 220.

Workup

  1. temperatureThe mixture was heated under an atmosphere of nitrogen at 85° C. for 90 minutes
  2. temperatureThe mixture was cooled to ambient temperature
  3. additionDowex resin (50WX4-400, 25 g) was added
  4. stirringthe mixture stirred for 1 hour at ambient temperature
  5. filtrationThe resin was collected by filtration
  6. washwashed with methanol (100 ml)
  7. stirringthe mixture stirred for 30 minutes
  8. filtrationThe mixture was filtered
  9. washthe residue washed with ammonia in methanol (2.3 N, 100 ml)
  10. concentrationThe combined filtrates were concentrated in vacuo
  11. customdried in vacuo (1 mbar, 60° C.) for 16 hours

Sources & evidence

ORD record
ord-848ee9a1914c410380a09d1c3e12e53d
Source dataset
uspto-grants-2009_12
Patent number
US07625908B2

Reaction notes

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