Hydrochloric Acid → 4-bromo-N-[4-(4-dimethylamino-quinazolin-2-ylamino)-phenyl]-2-trifluoromethoxy-benzenesulfonamide

HRID 1984895Notes

Reaction equation

HRID 1984895 reaction equation
C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]2[N:24]=[C:23]([N:25]([CH3:27])[CH3:26])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:16]=2)=[CH:10][CH:9]=1)(C)(C)C.Cl.C([O-])(O)=O.[Na+].[Br:35][C:36]1[CH:41]=[CH:40][C:39]([S:42](Cl)(=[O:44])=[O:43])=[C:38]([O:46][C:47]([F:50])([F:49])[F:48])[CH:37]=1>CCOC(C)=O.C(Cl)Cl>[Br:35][C:36]1[CH:41]=[CH:40][C:39]([S:42]([NH:7][C:8]2[CH:9]=[CH:10][C:11]([NH:14][C:15]3[N:24]=[C:23]([N:25]([CH3:26])[CH3:27])[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[N:16]=3)=[CH:12][CH:13]=2)(=[O:44])=[O:43])=[C:38]([O:46][C:47]([F:49])([F:48])[F:50])[CH:37]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 27364214-Bromo-2-(Trifluoromethoxy)Benzene-1-Sulfonyl ChlorideHCID 68846735[4-(4-Dimethylamino-quinazolin-2-ylamino)-phenyl]-carbamic acid tert-butyl ester

Product 1

HCID 577144994-bromo-N-[4-(4-dimethylamino-quinazolin-2-ylamino)-phenyl]-2-trifluoromethoxy-benzenesulfonamideYield 35%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8857Ethyl AcetateSolvent2×

Procedure

To a suspension of [4-(4-dimethylamino-quinazolin-2-ylamino)-phenyl]-carbamic acid tert-butyl ester (380 mg, 1.00 mmol) in EtOAc (4 mL) and CH2Cl2 (4 mL) was added 4 M hydrogen chloride in EtOAc (4 mL). The mixture was stirred at ambient temperature for 4 hr and concentrated to give a white solid. The solid was alkalized with saturated aqueous NaHCO3 filtered, washed with H2O and hexane, and dried at 50° C. under reduced pressure. To a solution of 4-bromo-2-trifluoromethoxy-benzenesulfonyl chloride (680 mg, 2.00 mmol) in CH2Cl2 (30 mL) was added PVP (8 mL). To the resulting suspension was added a solution of the above solid in CH2Cl2 (5 mL). The mixture was stirred at ambient temperature for 10.5 hr and filtered. The filtrate was washed with saturated aqueous NaHCO3, dried over MgSO4, filtered, concentrated, and purified by medium-pressure liquid chromatography (NH-silica gel, EtOAc) to give a solid. The solid was washed with Et2O and dried at 50° C. under reduced pressure to give 4-bromo-N-[4-(4-dimethylamino-quinazolin-2-ylamino)-phenyl]-2-trifluoromethoxy-benzenesulfonamide (202 mg, 35%) as a pale yellow solid.

Workup

  1. concentrationconcentrated
  2. customto give a white solid
  3. filtrationfiltered
  4. washwashed with H2O and hexane
  5. customdried at 50° C. under reduced pressure
  6. stirringThe mixture was stirred at ambient temperature for 10.5 hr
  7. filtrationfiltered
  8. washThe filtrate was washed with saturated aqueous NaHCO3
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. custompurified by medium-pressure liquid chromatography (NH-silica gel, EtOAc)
  13. customto give a solid
  14. washThe solid was washed with Et2O
  15. customdried at 50° C. under reduced pressure

Sources & evidence

ORD record
ord-72b3d931e2e949e5bf08b3a0c37d6016
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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