Hydrochloric Acid → N2-[1-(4-bromo-2-trifluoromethoxy-benzenesulfonyl)-piperidin-4-ylmethyl]-N4,N4-dimethyl-quinazoline-2,4-diamine

HRID 1984876Notes

Reaction equation

HRID 1984876 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][C:16]2[N:25]=[C:24]([N:26]([CH3:28])[CH3:27])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[N:17]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.C(N(C(C)C)CC)(C)C.[Br:39][C:40]1[CH:45]=[CH:44][C:43]([S:46](Cl)(=[O:48])=[O:47])=[C:42]([O:50][C:51]([F:54])([F:53])[F:52])[CH:41]=1>CCOC(C)=O.C(Cl)Cl>[Br:39][C:40]1[CH:45]=[CH:44][C:43]([S:46]([N:8]2[CH2:9][CH2:10][CH:11]([CH2:14][NH:15][C:16]3[N:25]=[C:24]([N:26]([CH3:27])[CH3:28])[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[N:17]=3)[CH2:12][CH2:13]2)(=[O:48])=[O:47])=[C:42]([O:50][C:51]([F:53])([F:52])[F:54])[CH:41]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 27364214-Bromo-2-(Trifluoromethoxy)Benzene-1-Sulfonyl ChlorideHCID 688493864-[(4-Dimethylamino-quinazolin-2-ylamino)-methyl]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 44401671N2-[1-(4-bromo-2-trifluoromethoxy-benzenesulfonyl)-piperidin-4-ylmethyl]-N4,N4-dimethyl-quinazoline-2,4-diamineYield 55%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

To a suspension of 4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-piperidine-1-carboxylic acid tert-butyl ester (500 mg, 1.30 mmol) in EtOAc (5 mL) was added 4 M hydrogen chloride in EtOAc (5 mL). The mixture was stirred at ambient temperature for 1 hr and concentrated to give a white solid. To a suspension of the above solid in CH2Cl2 (5 mL) was added diisopropylethylamine (480 μL, 2.76 mmol). The mixture was cooled to 4° C. and a solution of 4-bromo-2-trifluoromethoxy-benzenesulfonyl chloride (462 mg, 1.36 mmol) in CH2Cl2 (2 mL) was added below 5° C. The reaction mixture was stirred at 4° C. for 3 hr. The reaction was quenched with 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 flash chromatography (NH-silica gel, 14% to 20% EtOAc in hexane) to give N2-[1-(4-bromo-2-trifluoromethoxy-benzenesulfonyl)-piperidin-4-ylmethyl]-N4,N4-dimethyl-quinazoline-2,4-diamine (420 mg, 55%) as a yellow solid.

Workup

  1. concentrationconcentrated
  2. customto give a white solid
  3. temperatureThe mixture was cooled to 4° C.
  4. stirringThe reaction mixture was stirred at 4° C. for 3 hr
  5. customThe reaction was quenched with saturated aqueous NaHCO3 The aqueous layer
  6. extractionwas extracted with CHCl3 (three times)
  7. dry with materialThe combined organic layer was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by flash chromatography (NH-silica gel, 14% to 20% EtOAc in hexane)

Sources & evidence

ORD record
ord-ef646eca7e7541b2a96874426e1a0e1b
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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