Hydrochloric Acid → HCID 178483097, compound

HRID 1984873Notes

Reaction equation

HRID 1984873 reaction equation
C(OC(=O)[NH:7][C@H:8]1[CH2:13][CH2:12][C@H: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)[CH2:10][CH2:9]1)(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]([NH:7][C@H:8]2[CH2:13][CH2:12][C@H:11]([NH:14][C:15]3[N:24]=[C:23]([N:25]([CH3:27])[CH3:26])[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[N:16]=3)[CH2:10][CH2:9]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 81531Diisopropylethylamine2×HCID 27364214-Bromo-2-(Trifluoromethoxy)Benzene-1-Sulfonyl Chloride2×HCID 178483095HCID 178483095, compound

Product 1

HCID 178483097HCID 178483097, compoundYield 44.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of trans-[4-(4-dimethylamino-quinazolin-2-ylamino)-cyclohexyl]-carbamic 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 (7 mL) was added diisopropylethylamine (905 μL, 5.20 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 1.5 hr. To the reaction mixture was added a solution of 4-bromo-2-trifluoromethoxy-benzenesulfonyl chloride (88 mg, 0.26 mmol) in CH2Cl2 (0.5 mL) and the mixture was stirred at 4° C. for 1 hr. To the reaction mixture was added diisopropylethylamine (230 μL, 1.32 mmol) and the mixture was stirred at 4° C. for 1.5 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, 50% EtOAc in hexane) to give trans-4-bromo-N-[4-(4-dimethylamino-quinazolin-2-ylamino)-cyclohexyl]-2-trifluoromethoxy-benzenesulfonamid (339 mg, 44%) as a white 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 1.5 hr
  5. stirringthe mixture was stirred at 4° C. for 1 hr
  6. stirringthe mixture was stirred at 4° C. for 1.5 hr
  7. customThe reaction was quenched with saturated aqueous NaHCO3 The aqueous layer
  8. extractionwas extracted with CHCl3 (three times)
  9. dry with materialThe combined organic layer was dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. custompurified by flash chromatography (NH-silica gel, 50% EtOAc in hexane)

Sources & evidence

ORD record
ord-bdebc29eba4341ef8941abd3ec17cdd9
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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