4-Bromo-2-(Trifluoromethoxy)Benzene-1-Sulfonyl Chloride → 4-bromo-N-{4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-phenyl}-2-trifluoromethoxy-benzenesulfonamide

HRID 1984897Notes

Reaction equation

HRID 1984897 reaction equation
C(OC(=O)[NH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][NH:18][C:19]2[N:28]=[C:27]([N:29]([CH3:31])[CH3:30])[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:20]=2)=[CH:13][CH:12]=1)C1C=CC=CC=1.[Br:33][C:34]1[CH:39]=[CH:38][C:37]([S:40](Cl)(=[O:42])=[O:41])=[C:36]([O:44][C:45]([F:48])([F:47])[F:46])[CH:35]=1>CO.C(Cl)Cl.[Pd]>[Br:33][C:34]1[CH:39]=[CH:38][C:37]([S:40]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH2:17][NH:18][C:19]3[N:28]=[C:27]([N:29]([CH3:31])[CH3:30])[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]=3)=[CH:13][CH:12]=2)(=[O:42])=[O:41])=[C:36]([O:44][C:45]([F:47])([F:46])[F:48])[CH:35]=1

Participants

6

Reactant 2

HCID 27364214-Bromo-2-(Trifluoromethoxy)Benzene-1-Sulfonyl ChlorideHCID 68847095{4-[(4-Dimethylamino-quinazolin-2-ylamino)-methyl]-phenyl}-carbamic acid benzyl ester

Product 1

HCID 577144114-bromo-N-{4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-phenyl}-2-trifluoromethoxy-benzenesulfonamideYield 74.4%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of {4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-phenyl}-carbamic acid benzyl ester (318 mg, 0.744 mmol) in MeOH (3 mL) was added 5% Pd/C (30 mg). The mixture was stirred at 50° C. under hydrogen atmosphere for 41.5 hr, filtered through a pad of celite, and concentrated. To a solution of 4-bromo-2-trifluoromethoxy-benzenesulfonyl chloride (505 mg, 1.49 mmol) in CH2Cl2 (12 mL) was added PVP (6 mL). To the resulting suspension was added a solution of the above residue in CH2Cl2 (10 mL). The mixture was stirred at ambient temperature for 1.5 days, filtered, poured into saturated aqueous NaHCO3. The aqueous layer was extracted with CHCl3 (three times). The combined organic layer was dried over MgSO4, filtered, concentrated, and purified by medium-pressure liquid chromatography (NH-silica gel, 33% EtOAc in hexane) to give 4-bromo-N-{4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-phenyl}-2-trifluoromethoxy-benzenesulfonamide (330 mg, 74%) as a pale brown solid.

Workup

  1. filtrationfiltered through a pad of celite
  2. concentrationconcentrated
  3. stirringThe mixture was stirred at ambient temperature for 1.5 days
  4. filtrationfiltered
  5. additionpoured into saturated aqueous NaHCO3
  6. extractionThe aqueous layer was extracted with CHCl3 (three times)
  7. dry with materialThe combined organic layer was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by medium-pressure liquid chromatography (NH-silica gel, 33% EtOAc in hexane)

Sources & evidence

ORD record
ord-a2593c4bce7f42c9ba280837257486ad
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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