Pyridine → HCID 22478264, compound

HRID 1838543Notes

Reaction equation

HRID 1838543 reaction equation
FC(F)(F)S([O:6][S:7]([C:10]([F:13])([F:12])[F:11])(=[O:9])=[O:8])(=O)=O.Cl[N:17]([C:25]1[C:34]2[C:29](=[CH:30][C:31](O)=[C:32]([O:35][CH3:36])[CH:33]=2)[N:28]=[CH:27][N:26]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[F:24].N1C=CC=CC=1.C(Cl)[Cl:45]>>[Cl:45][C:21]1[CH:22]=[CH:23][C:18]([NH:17][C:25]2[C:34]3[C:29](=[CH:30][C:31]([O:6][S:7]([C:10]([F:11])([F:12])[F:13])(=[O:8])=[O:9])=[C:32]([O:35][CH3:36])[CH:33]=3)[N:28]=[CH:27][N:26]=2)=[C:19]([F:24])[CH:20]=1

Participants

5

Reactant 4

HCID 1049PyridineHCID 6344DichloromethaneHCID 67749Trifluoromethanesulfonic anhydrideHCID 1359906824-(Chloro-2-fluoroanilino)7-hydroxy-6-methoxyquinazoline

Product 1

HCID 22478264HCID 22478264, compoundYield 60%

Conditions

Temperature
0 °C

Procedure

Trifluoromethanesulphonic anhydride (0.55 ml, 3.3 mmol) was added to a stirred suspension of 4-(chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (959 mg, 3 mmol), (prepared as described for the starting material in Example 2), in methylene chloride (2.2 ml) and pyridine (2.2 ml) under argon at 0° C. The reaction mixture was stirred for 1 hour at 0° C., allowed to warm to ambient temperature and stirred for a further 1.5 hours. The volatiles were removed by evaporation, the residue was dissolved in ethyl acetate, washed with dilute hydrochloric acid and brine, dried (MgSO4) and the solvent removed by evaporation. The residue was triturated with ether/petroleum ether to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(trifluoromethylsulphonyloxy)quinazoline (270 mg, 60%) as a beige solid.

Workup

  1. custom(prepared
  2. customat 0° C
  3. temperatureto warm to ambient temperature
  4. stirringstirred for a further 1.5 hours
  5. customThe volatiles were removed by evaporation
  6. dissolutionthe residue was dissolved in ethyl acetate
  7. washwashed with dilute hydrochloric acid and brine
  8. dry with materialdried (MgSO4)
  9. customthe solvent removed by evaporation
  10. customThe residue was triturated with ether/petroleum ether

Sources & evidence

ORD record
ord-6a522119eca24c01afde90e127b59362
Source dataset
uspto-grants-2004_01
Patent number
US06673803B2

Reaction notes

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