7-Fluoro-6-nitroquinazolinone → 7-Fluoro-4-[(3-methylphenyl)-amino]-6-nitroquinazoline

HRID 1698950Notes

Reaction equation

HRID 1698950 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[N:7][C:8](=O)[NH:9]2)=[CH:4][C:3]=1[N+:13]([O-:15])=[O:14]>O=S(Cl)Cl.CN(C=O)C>[F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:13][C:3]3[CH:2]=[CH:11][CH:10]=[C:5]([CH3:6])[CH:4]=3)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[N+:13]([O-:15])=[O:14]

Participants

4

Reactant 1

HCID 181761687-Fluoro-6-nitroquinazolinone

Product 1

HCID 105420707-Fluoro-4-[(3-methylphenyl)-amino]-6-nitroquinazolineYield 175.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
20 °C

Procedure

A suspension of 7-fluoro-6-nitroquinazolone (2.40 g, 11.48 mmol) in neat SOCl2 (25 mL) containing 2 drops of DMF was refluxed for 3 hours until it became clear. The excess SOCl2 was then removed in vacuo and dry benzene was added to the residue and then distilled under reduced pressure to remove all traces of SOCl2 giving crude 4-chloro-7-fluoro-6-nitroquinazoline, which was dissolved in dry CH2Cl2 (50 mL) and added to a stirred solution of m-toluidine in isopropanol (i-PrOH) (30 mL). The reaction mixture was stirred at 20° C. for 30 minutes and then hexane (200 mL) was added to precipitate the product as the HCl salt. The precipitate was filtered, washed with hexane, and then dissolved in MeOH/H2O (4:1, 150 mL) with gentle warming. Excess Et3N was then added to the solution followed by water (400 mL) to precipitate the product as the free base which was then filtered, washed with water and dried under reduced pressure to give 7-fluoro-4-[(3-methylphenyl)-amino]-6-nitroquinazoline (3.01 g, 88%) as a yellow powder, mp (CH2Cl2/hexane) 191-192° C.

Workup

  1. temperaturewas refluxed for 3 hours until it
  2. customThe excess SOCl2 was then removed in vacuo and dry benzene
  3. additionwas added to the residue
  4. distillationdistilled under reduced pressure
  5. customto remove all traces of SOCl2 giving crude 4-chloro-7-fluoro-6-nitroquinazoline, which
  6. dissolutionwas dissolved in dry CH2Cl2 (50 mL)
  7. additionadded to a stirred solution of m-toluidine in isopropanol (i-PrOH) (30 mL)
  8. additionhexane (200 mL) was added
  9. customto precipitate the product as the HCl salt
  10. filtrationThe precipitate was filtered
  11. washwashed with hexane
  12. dissolutiondissolved in MeOH/H2O (4:1, 150 mL) with gentle warming
  13. additionExcess Et3N was then added to the solution
  14. customto precipitate the product as the free base which
  15. filtrationwas then filtered
  16. washwashed with water
  17. customdried under reduced pressure

Sources & evidence

ORD record
ord-d014143cf7ff43d0b92366ea534682bb
Source dataset
uspto-grants-2002_02
Patent number
US06344459B1

Reaction notes

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