Diisopropylethylamine → HCID 178483074, compound

HRID 1984871Notes

Reaction equation

HRID 1984871 reaction equation
C(OC(=O)[NH:10][C@H:11]1[CH2:16][CH2:15][C@H: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)[CH2:13][CH2:12]1)C1C=CC=CC=1.C(N(C(C)C)CC)(C)C.[Br:42][C:43]1[CH:48]=[CH:47][C:46]([S:49](Cl)(=[O:51])=[O:50])=[C:45]([O:53][C:54]([F:57])([F:56])[F:55])[CH:44]=1>CO.C(Cl)Cl.[Pd]>[Br:42][C:43]1[CH:48]=[CH:47][C:46]([S:49]([NH:10][C@H:11]2[CH2:16][CH2:15][C@H: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)[CH2:13][CH2:12]2)(=[O:51])=[O:50])=[C:45]([O:53][C:54]([F:57])([F:56])[F:55])[CH:44]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 27364214-Bromo-2-(Trifluoromethoxy)Benzene-1-Sulfonyl ChlorideHCID 178483072HCID 178483072, compound

Product 1

HCID 178483074HCID 178483074, compoundYield 81%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
50 °C

Procedure

To a suspension of trans-{4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-cyclohexyl}-carbamic acid benzyl ester (500 mg, 1.15 mmol) in MeOH (5 mL) was added 5% Pd/C (50 mg). The mixture was stirred at ambient temperature under hydrogen atmosphere for 2 hr, at 50° C. for 8 hr, and at ambient temperature for 10.5 hr, filtered, and concentrated to give a colorless oil. To a solution of the above oil in CH2Cl2 (5 mL) was added diisopropylethylamine (420 μL, 2.41 mmol). The mixture was cooled to 4° C. and a solution of 4-bromo-2-trifluoromethoxy-benzenesulfonyl chloride (431 mg, 1.27 mmol) in CH2Cl2 (2 mL) was added below 5° C. The reaction 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, 33% to 50% EtOAc in hexane) to give trans-4-bromo-N-{4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-cyclohexyl}-2-trifluoromethoxy-benzenesulfonamide (560 mg, 81%) as a pale yellow solid.

Workup

  1. waitat ambient temperature for 10.5 hr
  2. filtrationfiltered
  3. concentrationconcentrated
  4. customto give a colorless oil
  5. temperatureThe mixture was cooled to 4° C.
  6. stirringThe reaction 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, 33% to 50% EtOAc in hexane)

Sources & evidence

ORD record
ord-6d5a1582c1c8490cad987748ae6810d4
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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