Diisopropylethylamine → HCID 11342160, compound

HRID 1984872Notes

Reaction equation

HRID 1984872 reaction equation
C([N:8]1[CH2:13][CH2:12][CH: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)C1C=CC=CC=1.C(N(C(C)C)CC)(C)C.[Br:37][C:38]1[CH:43]=[CH:42][C:41]([S:44](Cl)(=[O:46])=[O:45])=[C:40]([O:48][C:49]([F:52])([F:51])[F:50])[CH:39]=1>CO.C(Cl)Cl.[OH-].[OH-].[Pd+2]>[Br:37][C:38]1[CH:43]=[CH:42][C:41]([S:44]([N:8]2[CH2:9][CH2:10][CH: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)[CH2:12][CH2:13]2)(=[O:46])=[O:45])=[C:40]([O:48][C:49]([F:51])([F:50])[F:52])[CH:39]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 27364214-Bromo-2-(Trifluoromethoxy)Benzene-1-Sulfonyl ChlorideHCID 68850270HCID 68850270, compound

Product 1

HCID 11342160HCID 11342160, compoundYield 43%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of N2-(1-benzyl-piperidin-4-yl)-N4,N4-dimethyl-quinazoline-2,4-diamine (500 mg, 1.38 mmol) in MeOH (5 mL) was added 20% Pd(OH)2 (100 mg). The mixture was stirred at ambient temperature under hydrogen atmosphere for 1.5 hr, at 50° C. for 8 hr, at ambient temperature for 16.5 hr, filtered through a pad of celite, and concentrated. To a solution of the residue in CH2Cl2 (5 mL) was added diisopropylethylamine (510 μL, 2.93 mmol). The mixture was cooled to 4° C. and a solution of 4-bromo-2-trifluoromethoxy-benzenesulfonyl chloride (493 mg, 1.45 mmol) in CH2Cl2 (2 mL) was added below 5° C. The reaction mixture was stirred at 4° C. for 2 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% EtOAc in hexane) to give N2-[1-(4-bromo-2-trifluoromethoxy-benzenesulfonyl)-piperidin-4-yl]-N4,N4-dimethyl-quinazoline-2,4-diamine (339 mg, 43%) as a pale yellow solid.

Workup

  1. filtrationfiltered through a pad of celite
  2. concentrationconcentrated
  3. temperatureThe mixture was cooled to 4° C.
  4. stirringThe reaction mixture was stirred at 4° C. for 2 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, 33% EtOAc in hexane)

Sources & evidence

ORD record
ord-10910b6674384e3cb13b78410cdcc740
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

Loading…