Sodium hydride → HCID 23505665, compound

HRID 1884385Notes

Reaction equation

HRID 1884385 reaction equation
[CH2:1]1[O:13][C:12]2[CH:11]=[C:10]3[C:5]([C:6]([C:15]4[CH:20]=[CH:19][C:18]5[O:21][CH2:22][O:23][C:17]=5[CH:16]=4)=[N:7][C:8](=[O:14])[NH:9]3)=[CH:4][C:3]=2[O:2]1.[H-].[Na+].Br[CH2:27][CH:28]1[CH2:30][CH2:29]1>CN(C=O)C>[CH2:1]1[O:13][C:12]2[CH:11]=[C:10]3[C:5]([C:6]([C:15]4[CH:20]=[CH:19][C:18]5[O:21][CH2:22][O:23][C:17]=5[CH:16]=4)=[N:7][C:8]([O:14][CH2:27][CH:28]4[CH2:30][CH2:29]4)=[N:9]3)=[CH:4][C:3]=2[O:2]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 23505652HCID 23505652, compound

Product 1

HCID 23505665HCID 23505665, compoundYield 16.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a suspension of 6,7-methylenedioxy-4-(3,4-methylenedioxyphenyl)-quinazolin-2-one (310 mg, 1.00 mmol) in DMF (7 mL) was added NaH (97%, 32 mg, 1.33 mmol). The mixture was stirred at 25° C. for 45 min, then (bromomethyl)cyclopropane (0.2 mL, 2.0 mmol) was added. The resulting mixture was then heated at 100° C. for 6 h, cooled to rt, poured into ice-water (50 mL) and stirred for 30 min. The resulting precipitate was collected by filtration and the solid was dissolved in ethyl acetate. The solution was washed with water and brine, dried over anhydrous MgSO4, and the solvent was removed in vacuo. This crude product was separated by chromatography in silica gel. Elution with hexane:acetone (65:35) gave 6,7-methylenedioxy-4-(3,4-methylenedioxyphenyl)-2-(cyclopropylmethoxy)-quinazoline as yellow solid (60 mg); mp 175-182° C.; 1H NMR (CDCl3) 7.31 (s, 1H), 7.21-7.25 (m, 3H), 7.14 (s, 1H), 6.93-6.96 (d, J=8.4, 1H), 6.09 (s, 2H), 6.06 (s, 2H), 4.29-4.31 (t, J=7.2, 2H), 3.2 (s, 1H); 0.63 (s, 2H), 0.41 (s, 2H); C20H16N2O5; C, 65.93; H, 4.43; N, 7.69. Further elution with the same solvents gave 1-cyclopropylmethyl-6,7-methylenedioxy-4-(3,4-methylenedioxyphenyl)quinazolin-2(1H)-one as pale yellow solid (75 mg); mp 255-260° C.; 1H NMR (CDCl3) 7.18-7.36 (m, 3H), 6.82-7.02 (m, 3H), 6.11 (s, 2H), 6.06 (s, 2H), 4.22 (d, J=6.8, 2H), 1.18-1.40 (m, 1H), 0.41-0.78 (m, 4H); C20H16N2O5; C, 65.93; H, 4.43; N, 7.69.

Workup

  1. temperatureThe resulting mixture was then heated at 100° C. for 6 h
  2. temperaturecooled to rt
  3. stirringstirred for 30 min
  4. filtrationThe resulting precipitate was collected by filtration
  5. dissolutionthe solid was dissolved in ethyl acetate
  6. washThe solution was washed with water and brine
  7. dry with materialdried over anhydrous MgSO4
  8. customthe solvent was removed in vacuo
  9. customThis crude product was separated by chromatography in silica gel
  10. washElution with hexane:acetone (65:35)

Sources & evidence

ORD record
ord-201055d9cfe647df877dab27c499dbe9
Source dataset
uspto-grants-2004_07
Patent number
US06765006B2

Reaction notes

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