Hydrochloric Acid → 1-{4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}ethanone

HRID 1867759Notes

Reaction equation

HRID 1867759 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:16]=1[O:17][CH3:18])[N:13]=[CH:12][N:11]=[C:10]2[NH:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:21]=1[F:27])(=O)=O.[CH:30]([O:32]CCCC)=[CH2:31].C(N(CC)CC)C.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl.C(=O)([O-])O.[Na+]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:26][C:22]1[C:21]([F:27])=[C:20]([NH:19][C:10]2[C:9]3[C:14](=[CH:15][C:16]([O:17][CH3:18])=[C:7]([C:30](=[O:32])[CH3:31])[CH:8]=3)[N:13]=[CH:12][N:11]=2)[CH:25]=[CH:24][CH:23]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8108Butyl vinyl etherHCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 516892Sodium BicarbonateHCID 160500604-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl trifluoromethanesulfonate

Product 1

HCID 579798001-{4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}ethanoneYield 74%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl trifluoromethanesulfonate, (described in Example 1 preparation of starting materials), (3 g, 6.64 mmol) was dissolved in dimethylformamide (21 ml) and n-butyl vinyl ether (4.3 ml, 33.2 mmol), triethylamine (2.3 ml, 16.6 mmol), 1,3-bis(diphenylphosphino)propane (438 mg, 1.06 mmol) and palladium acetate (223 mg, 1 mmol) added. The mixture was heated at 80° C. for 2 hours, allowed to cool and stirred at room temperature over night. 2M aqueous hydrochloric acid (24 ml) was added and the mixture stirred for 0.5 hours. The mixture was basified with saturated aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The organic extracts were washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The resulting solid was suspended in methanol and filtered to give 1-{4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}ethanone (1.7 g, 74%) as a pale yellow solid; 1H NMR (spectrum): (DMSO d6) 2.62 (s, 3H); 4.02 (s, 3H); 7.27 (m, 2H); 7.49 (t, 2H); 8.48 (s, 1H); 8.72 (s, 1H); 10.19 (s, 1H). Mass Spectrum: (M+H)+ 346.

Workup

  1. temperatureto cool
  2. stirringthe mixture stirred for 0.5 hours
  3. extractionextracted with ethyl acetate
  4. washThe organic extracts were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. filtrationfiltered

Sources & evidence

ORD record
ord-53941038b2724b56986e858ba03d47ce
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Reaction notes

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