Phosphorus oxychloride → 2-Chloro-4-(1-methylpropylamino)-6-nitroquinazoline

HRID 1250600

Reaction equation

HRID 1250600 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=O)[NH:8][C:7]2=O)([O-:3])=[O:2].P(Cl)(Cl)([Cl:18])=O.C(N(C(C)C)C=O)(C)C.[CH3:30][CH:31]([NH2:34])[CH2:32][CH3:33]>O>[Cl:18][C:9]1[N:8]=[C:7]([NH:34][CH:31]([CH3:30])[CH2:32][CH3:33])[C:6]2[C:11](=[CH:12][CH:13]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[N:10]=1

Participants

6

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 24874Sec-ButylamineHCID 75912N,N-bis(1-methylethyl)formamideHCID 8169826-Nitro-2,4(1H,3H)-quinazolinedione

Product 1

HCID 183264352-Chloro-4-(1-methylpropylamino)-6-nitroquinazolineYield 68.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To 250 mg (1.21 mmol) of 6-nitroquinazoline-2,4(1H,3H)-dione were added 5.00 ml (53.64 mmol) of phosphorus oxychloride and 0.18 ml (1.21 mmol) of diisopropylformamide, and the resulting mixture was subjected to heating under reflux for 24 hours. After phosphorus oxychloride was removed in vacuo, the mixture was dissolved in 5 ml of acetonitrile, followed by addition of 1.23 ml (12.10 mmol) of 1-methylpropylamine under ice cooling and stirring under ice cooling for 30 minutes. To the reaction solution was added water, followed by extraction with ethyl acetate, washing with brine and drying over anhydrous sodium sulfate. After the solvent was distilled off, the residue was purified by a silica gel column to give 234 mg (68.9%) of the title compound.

Workup

  1. temperatureto heating
  2. temperatureunder reflux for 24 hours
  3. customAfter phosphorus oxychloride was removed in vacuo
  4. dissolutionthe mixture was dissolved in 5 ml of acetonitrile
  5. extractionfollowed by extraction with ethyl acetate
  6. washwashing with brine
  7. dry with materialdrying over anhydrous sodium sulfate
  8. distillationAfter the solvent was distilled off
  9. customthe residue was purified by a silica gel column

Sources & evidence

ORD record
ord-729c932aa68840e18c42ecf0c7580992
Source dataset
uspto-grants-2002_01
Patent number
US06339089B2

Linked notes

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