Phosphorus oxychloride → 4-Quinazolinamine, N-(4-methoxyphenyl)-N,2-dimethyl-6-nitro-

HRID 1876128Notes

Reaction equation

HRID 1876128 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[C:4]([CH3:15])[N:3]=1.C[C:17]1NC(=O)[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([N+]([O-])=O)[CH:23]=2)[N:18]=1.C(N(C(C)C)CC)(C)C.P(Cl)(Cl)(Cl)=O.[C:45]([O-])(O)=[O:46].[Na+]>C1(C)C=CC=CC=1>[CH3:45][O:46][C:22]1[CH:21]=[CH:20][C:19]([N:18]([C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=3)[N:5]=[C:4]([CH3:15])[N:3]=2)[CH3:17])=[CH:24][CH:23]=1

Participants

7

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 249038664-Chloro-2-methyl-6-nitroquinazolineHCID 1354088002-Methyl-6-nitro-3H-quinazolin-4-one

Product 1

HCID 112787684-Quinazolinamine, N-(4-methoxyphenyl)-N,2-dimethyl-6-nitro-Yield 60%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

4-Chloro-2-methyl-6-nitro-quinazoline. A mixture of 2-methyl-6-nitro-quinazoline-4-one (100 mg, 0.49 mmol) and diisopropylethylamine (250 uL) in 3 mL of toluene was heated to 120° C. for 1 h, then phosphorylchloride (50 uL, 0.54 mmol) was added and the mixture was heated at 80° C. for 3 h. The reaction mixture was cooled to room temperature and poured into ice (about 15 g), basified with saturated NaHCO3 and extracted with 75 mL of ethyl acetate. The organic layer was washed with water (50 mL), 1N citric acid (50 mL), water (50 mL) and saturated NaCl, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by column chromatography (15% ethyl acetate/hexanes) on silica gel to give the title compound (65.5 mg, 0.29 mmol, 60%). 1H NMR (CDCl3): 9.17 (d, J=2.4, 1H), 8.69 (dd, J=9.3, 2.4, 1H), 8.13 (d, J=9.3, 1H), 2.93 (s, 3H).

Workup

  1. temperaturethe mixture was heated at 80° C. for 3 h
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionextracted with 75 mL of ethyl acetate
  4. washThe organic layer was washed with water (50 mL), 1N citric acid (50 mL), water (50 mL) and saturated NaCl
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (15% ethyl acetate/hexanes) on silica gel

Sources & evidence

ORD record
ord-1dfa393524d74cb29de0f923dafb584e
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

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