Sodium hydride → 3-(2-chlorophenyl)-6-ethoxycarbonyl-5,7-dimethyl-1-[3-(N-benzyl-N-methylamino)propyl]-2,4(1H, 3H)-quinazolinedione

HRID 1995647Notes

Reaction equation

HRID 1995647 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]1[C:19](=[O:20])[C:18]2[C:13](=[CH:14][C:15]([CH3:27])=[C:16]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:17]=2[CH3:21])[NH:12][C:11]1=[O:28].Cl.[CH2:30]([N:37]([CH2:39][CH2:40][CH2:41]Cl)[CH3:38])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>CN(C)C=O>[Cl:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]1[C:19](=[O:20])[C:18]2[C:13](=[CH:14][C:15]([CH3:27])=[C:16]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:17]=2[CH3:21])[N:12]([CH2:41][CH2:40][CH2:39][N:37]([CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH3:38])[C:11]1=[O:28]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1336033-(2-chlorophenyl)-6-ethoxycarbonyl-5,7-dimethyl-2,4(1H,3H)-quinazolidinedioneHCID 24189321Benzyl(3-chloropropyl)methylamine hydrochloride

Product 1

HCID 130507283-(2-chlorophenyl)-6-ethoxycarbonyl-5,7-dimethyl-1-[3-(N-benzyl-N-methylamino)propyl]-2,4(1H, 3H)-quinazolinedioneYield 66.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A portion (96 mg) of 50% sodium hydride suspension in mineral oil was added to a solution of 3-(2-chlorophenyl)-6-ethoxycarbonyl-5,7-dimethyl-2,4(1H, 3H)-quinazolinedione (372 mg) in dimethylformamide (20 ml). After stirring the mixture at 100° C. for one hour, 3-(N-benzyl-N-methylamino)propyl chloride hydrochloride (320 mg) was added. The mixture was heated to 140°-145° C. and maintained at this temperature for 6 hours with stirring. The mixture was concentrated under reduced pressure, and the mixture was then partitioned between CHCl3 and 10% aqueous K2CO3 solution. The CHCl3 phase was separated, dried over MgSO4 and concentrated. The residue was chromatographed over a column of silica gel, and the fractions eluted with CHCl3 -methanol (v/v, 9:1) were concentrated and recrystallized from diethyl ether/n-hexane to give 3-(2-chlorophenyl)-6-ethoxycarbonyl-5,7-dimethyl-1-[3-(N-benzyl-N-methylamino)propyl]-2,4(1H, 3H)-quinazolinedione (355 mg, 66.5%) melting at 145°-146° C. After treating the crystals with ethanol containing hydrogen chloride and recrystallizing from ethanol/diethyl ether, the hydrochloride melting at 207°-209° C. was obtained.

Workup

  1. temperatureThe mixture was heated to 140°-145° C.
  2. temperaturemaintained at this temperature for 6 hours
  3. stirringwith stirring
  4. concentrationThe mixture was concentrated under reduced pressure
  5. customthe mixture was then partitioned between CHCl3 and 10% aqueous K2CO3 solution
  6. customThe CHCl3 phase was separated
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe residue was chromatographed over a column of silica gel
  10. washthe fractions eluted with CHCl3 -methanol (v/v, 9:1)
  11. concentrationwere concentrated
  12. customrecrystallized from diethyl ether/n-hexane

Sources & evidence

ORD record
ord-ce1fa8169cf9401db1c23ebb70de50c1
Source dataset
uspto-grants-1983_09
Patent number
US04405623

Reaction notes

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