2-Methoxyethanol → 4-(4-Chloro-2-fluoroanilino)-7-(2-methoxyethoxy)-6-nitroquinazoline

HRID 1838538Notes

Reaction equation

HRID 1838538 reaction equation
[Na].[CH3:2][O:3][CH2:4][CH2:5][OH:6].Cl.Cl[C:9]1[CH:18]=[C:17]2[C:12]([C:13]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=3[F:27])=[N:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[N+:28]([O-:30])=[O:29]>C(O)(=O)C.O>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([NH:19][C:13]2[C:12]3[C:17](=[CH:18][C:9]([O:6][CH2:5][CH2:4][O:3][CH3:2])=[C:10]([N+:28]([O-:30])=[O:29])[CH:11]=3)[N:16]=[CH:15][N:14]=2)=[C:21]([F:27])[CH:22]=1

Participants

6

Reactant 3

HCID 80192-MethoxyethanolHCID 5360545SodiumHCID 224782507-Chloro-4-(4-chloro-2-fluoroanilino)-6-nitroquinazoline hydrochloride

Product 1

HCID 187534234-(4-Chloro-2-fluoroanilino)-7-(2-methoxyethoxy)-6-nitroquinazolineYield 60%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

Sodium (148 mg, 6.4 mmol) was added to 2-methoxyethanol (10 ml), the mixture stirred for 15 minutes to give a complete solution and the volatiles removed by evaporation. The residue was dissolved in DMSO (5 ml) and 7-chloro-4-(4-chloro-2-fluoroanilino)-6-nitroquinazoline hydrochloride (500 mg, 1.3 mmol) was added. The mixture was stirred at ambient temperature for 18 hours then diluted with a solution of acetic acid (1 ml) in water (20 ml). The resulting precipitate was collected by filtration, washed with water, dried and purified by column chromatography eluting with methylene chloride/methanol (96/4). The purified product was recrystallised from methylene chloride/isohexane to give 4-(4-chloro-2-fluoroanilino)-7-(2-methoxyethoxy)-6-nitroquinazoline (304 mg, 60%) as a yellow solid.

Workup

  1. customto give a complete solution
  2. customthe volatiles removed by evaporation
  3. dissolutionThe residue was dissolved in DMSO (5 ml)
  4. stirringThe mixture was stirred at ambient temperature for 18 hours
  5. filtrationThe resulting precipitate was collected by filtration
  6. washwashed with water
  7. customdried
  8. custompurified by column chromatography
  9. washeluting with methylene chloride/methanol (96/4)
  10. customThe purified product was recrystallised from methylene chloride/isohexane

Sources & evidence

ORD record
ord-a0f60cb3763b4b51bad4b44387df5c47
Source dataset
uspto-grants-2004_01
Patent number
US06673803B2

Reaction notes

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