Sodium Hydroxide → HCID 9951860, compound

HRID 1884394Notes

Reaction equation

HRID 1884394 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]C[O:24][C:17]=5[CH:16]=4)=[N:7][C:8](=[O:14])[NH:9]3)=[CH:4][C:3]=2[O:2]1.CC([O-])(C)C.[K+].Cl.[CH3:32][N:33]([CH3:37])[CH2:34][CH2:35]Cl.[OH-].[Na+]>CN(C=O)C.C1C=CC=CC=1>[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:24][C:17]=5[CH:16]=4)=[N:7][C:8]([O:14][CH2:35][CH2:34][N:33]([CH3:37])[CH3:32])=[N:9]3)=[CH:4][C:3]=2[O:2]1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 11636816N,N-Dimethylaminoethyl chloride hydrochlorideHCID 23505626HCID 23505626, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 9951860HCID 9951860, compound

Reagents, catalysts & solvents 2

HCID 241BenzeneSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a suspension of 6,7-methylenedioxy-4-(3,4-ethylenedioxyphenyl)-quinazolin-2-one (400 mg, 1.29 mmol) in DMF (15 mL) was added KOtBu (95%, 232 mg, 2.06 mmol) at room temp. and stirred for 45 minutes. Separately, a solution of 2-dimethylaminoethyl chloride hydrochloride (371 mg, 2.58 mmol) in benzene (12 mL) was treated with a solution of 2 N NaOH (10 mL). The benzene layer, which contained the free base, was dried over anhydrous MgSO4, and added to the above reaction mixture at room temp. The resulting mixture was then heated at 110° C. under argon gas for 15 h. The reaction mixture was then poured into ice-water (50 mL). It was stirred for 30 minutes. The resulting precipitate was collected by filtration. It was dissolved in ethyl acetate. The organic layer was washed with water and brine. Bier being dried over anhydrous MgSO4 the solvent was removed in vacuo. This crude product was then dissolved in a small amount of CHCl3 and poured on a column of silica gel. Elution with acetone:CH2Cl2:MeOH (90:5:5) gave 6,7-methylenedioxy-4-(3,4-methylenedioxyphenyl)-2-(2-(dimethylamino) ethoxy)-quinazoline as a first fraction as yellow solid (110 mg); C21H21N3O5; mp120-123° C. 1H NMR (CDCl3) δ 7.33 (s, 1H), 7.20-7.27 (m, 2H), 7.14 (s, 1H), 6.95 (d, J=7.80 Hz, 1H), 6.08 (s, 2H), 4.59 (m, 2H), 4.32 (s, 4H), 2.83 (m, 2H), 2.38 (s, 6H). Further elution with the same solvent mixture gave 1-(2-(dimethylamino)ethyl)-6,7-methylenedioxy-4-(3,4-ethylenedioxyphenyl)-quinazolin-2(1H)-one as pale yellow solid (90 mg); C21H21N3O5; mp 220-225° C. 1H NMR (CDCl3) δ 7.24 (s, 1H), 7.23 (s, 1H), 7.16-7.19 (m, 2H), 6.95 (d, J=8.4 Hz, 1H), 6.09 (s, 2H), 4.40 (m, 2H), 4.31 (s, 4H), 2.76 (m, 2H), 2.43 (s, 6H).

Workup

  1. dry with materialwas dried over anhydrous MgSO4
  2. additionadded to the above reaction mixture at room temp
  3. additionThe reaction mixture was then poured into ice-water (50 mL)
  4. stirringIt was stirred for 30 minutes
  5. filtrationThe resulting precipitate was collected by filtration
  6. dissolutionIt was dissolved in ethyl acetate
  7. washThe organic layer was washed with water and brine
  8. dry with materialBier being dried over anhydrous MgSO4 the solvent
  9. customwas removed in vacuo
  10. dissolutionThis crude product was then dissolved in a small amount of CHCl3
  11. additionpoured on a column of silica gel
  12. washElution with acetone:CH2Cl2:MeOH (90:5:5)

Sources & evidence

ORD record
ord-6a3274dcb3f14968b4668a1124cd8416
Source dataset
uspto-grants-2004_07
Patent number
US06765006B2

Reaction notes

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