Sodium hydride → 6-((1S,4S)-5-Methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)-3-((5-methylisoxazol-3-yl)methyl)quinazolin-4(3H)-one

HRID 77408Notes

Reaction equation

HRID 77408 reaction equation
[CH3:1][N:2]1[CH2:7][C@@H:6]2[CH2:8][C@H:3]1[CH2:4][N:5]2[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]=[CH:14][NH:13][C:12]2=[O:19].[H-].[Na+].Br[CH2:23][C:24]1[CH:28]=[C:27]([CH3:29])[O:26][N:25]=1>CN(C)C=O>[CH3:1][N:2]1[CH2:7][C@@H:6]2[CH2:8][C@H:3]1[CH2:4][N:5]2[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]=[CH:14][N:13]([CH2:23][C:24]1[CH:28]=[C:27]([CH3:29])[O:26][N:25]=1)[C:12]2=[O:19]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27763043-(Bromomethyl)-5-methylisoxazoleHCID 1363502746-((1S,4S)-5-Methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)quinazolin-4(3H)-one

Product 1

HCID 699281986-((1S,4S)-5-Methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)-3-((5-methylisoxazol-3-yl)methyl)quinazolin-4(3H)-oneYield 66.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-((1S,4S)-5-Methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)quinazolin-4(3H)-one (Example 10A) (150 mg, 0.583 mmol) in dimethylformamide was cooled to 0° C. added and sodium hydride (21 mg, 0.875 mmol) was added, after 5 minutes 3-bromomethyl-5-methylisoxazole (75 mg, 0.426 mmol) was added and the reaction stirred at room temp for 1 h. The reaction was quenched with ammonium chloride and the dimethylformamide evaporated off. The residue was dissolved in 10% methanol in dichloromethane and dried over sodium sulphate before evaporation to dryness. The product was purified by silica chromatography, elueting with 10% methanol in dichloromethane to afford 6-((1S,4S)-5-Methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)-3-((5-methylisoxazol-3-yl)methyl)quinazolin-4(3H)-one (0.10 g, 0.284 mmol).

Workup

  1. additionadded
  2. additionwas added
  3. customThe reaction was quenched with ammonium chloride
  4. customthe dimethylformamide evaporated off
  5. dissolutionThe residue was dissolved in 10% methanol in dichloromethane
  6. dry with materialdried over sodium sulphate before evaporation to dryness
  7. customThe product was purified by silica chromatography

Sources & evidence

ORD record
ord-006cbcdb9f2347bfba4aa2918d686980
Source dataset
uspto-grants-2014_09
Patent number
US08841289B2

Reaction notes

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