Phosphorus oxychloride → 5-Bromo-4-chloro-7-methyl-8-nitroquinazoline

HRID 1469761Notes

Reaction equation

HRID 1469761 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]([CH3:12])[C:9]([N+:13]([O-:15])=[O:14])=[C:8]2[C:3]=1[C:4](=O)[NH:5][CH:6]=[N:7]2.O=P(Cl)(Cl)[Cl:19]>>[Br:1][C:2]1[CH:11]=[C:10]([CH3:12])[C:9]([N+:13]([O-:15])=[O:14])=[C:8]2[C:3]=1[C:4]([Cl:19])=[N:5][CH:6]=[N:7]2

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 1363368225-bromo-7-methyl-8-nitroquinazolin-4(3H)-one

Product 1

HCID 866922505-Bromo-4-chloro-7-methyl-8-nitroquinazoline

Procedure

A solution of 5-bromo-7-methyl-8-nitroquinazolin-4(3H)-one (200 mg, 0.71 mmol) in POCl3 (4 mL) was heated at reflux for 4 h. Then the reaction mixture was concentrated and the residue was co-evaporated with toluene and dried to afford 5-bromo-4-chloro-7-methyl-8-nitroquinazoline which was dissolved in THF (5 mL). Then the solution was treated with 3-(trifluoromethyl)aniline (457 mg, 2.84 mmol) and DIPEA (458 mg, 3.55 mmol) at 0° C. and the reaction mixture was stirred at rt for 12 h before it was quenched with water and was extracted with EtOAc. The organic layer was washed with brine, separated, dried, filtered, concentrated and purified by column chromatography to afford 215 mg of the title product. 1H NMR (300 MHz, DMSO-d6): δ 10.36 (s, 1H), 9.15 (s, 1H), 8.72 (s, 1H), 8.29 (s, 1H), 8.23 (d, J=8.4 Hz, 1H), 7.67 (t, J=7.8 Hz, 1H), 7.53 (d, J=7.8 Hz, 1H), 2.47 (s, 3H); MS (m/z): 427.17 (M)+.

Workup

  1. temperatureat reflux for 4 h
  2. concentrationThen the reaction mixture was concentrated
  3. customdried

Sources & evidence

ORD record
ord-3d1a00c0bb844278ab22b6fbe0857d90
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Reaction notes

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