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Pyridine → Trifluoromethylsulphonyloxyquinazoline

HRID 547179
Notes
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Reaction equation

HRID 547179 reaction equation
[F:1][C:2]([F:15])([F:14])[S:3]([O:6]S(C(F)(F)F)(=O)=O)(=[O:5])=[O:4].ClN([C:25]1[C:34]2[C:29](=[CH:30][C:31](O)=[C:32](OC)[CH:33]=2)[N:28]=[CH:27][N:26]=1)C1C=CC=CC=1F.N1C=CC=CC=1>C(Cl)Cl>[F:1][C:2]([F:15])([F:14])[S:3]([O:6][C:27]1[N:26]=[CH:25][C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[N:28]=1)(=[O:5])=[O:4]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

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

Product 1

HCID 53804830TrifluoromethylsulphonyloxyquinazolineYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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-6methoxyquinazoline (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-(trifluoromethylsulphonyloxyquinazoline (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-5e219fe47c4b4ffbaf3a6da4c3649018
Source dataset
uspto-grants-2011_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
USRE042353E1

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes