Hydrochloric Acid → HCID 178483090, compound

HRID 1984909Notes

Reaction equation

HRID 1984909 reaction equation
[ClH:1].Cl.Br[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][NH:12][C@@H:13]2[CH2:18][CH2:17][C@H:16]([NH:19][C:20]3[N:29]=[C:28]([N:30]([CH3:32])[CH3:31])[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[N:21]=3)[CH2:15][CH2:14]2)=[C:6]([O:33][C:34]([F:37])([F:36])[F:35])[CH:5]=1.Cl>CCO.CCOC(C)=O.[Pd]>[ClH:1].[ClH:1].[CH3:32][N:30]([CH3:31])[C:28]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=[C:20]([NH:19][C@H:16]2[CH2:17][CH2:18][C@@H:13]([NH:12][CH2:11][CH2:10][C:7]3[CH:8]=[CH:9][CH:4]=[CH:5][C:6]=3[O:33][C:34]([F:37])([F:36])[F:35])[CH2:14][CH2:15]2)[N:29]=1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 178483089HCID 178483089, compound

Product 1

HCID 178483090HCID 178483090, compoundYield 95.2%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of cis-N2-{4-[2-(4-bromo-2-trifluoromethoxy-phenyl)-ethylamino]-cyclohexyl}-N4,N4-dimethyl-quinazoline-2,4-diamine dihydrochloride obtained in step B of example 37 (250 mg, 0.4 mmol) in EtOH (5 mL) was added 10% Pd/C (75 mg). The mixture was stirred at ambient temperature under hydrogen atmosphere for 17 hr, 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 flash chromatography (NH-silica gel, 50% EtOAc in hexane) to give a colorless oil. To a solution of above oil in EtOAc (4 mL) was added 4 M hydrogen chloride in EtOAc (0.25 mL). The mixture was stirred at ambient temperature for 1 hr and concentrated. The residue was suspended with Et2O (15 mL) and stirred at ambient tempareture for 1 hr. The solid was collected by filtration, washed with Et20, and dried under reduced pressure to give cis-N4,N4-dimethyl-N2-{4-[2-(2-trifluoromethoxy-phenyl)-ethylamino]-cyclohexyl}-quinazoline-2,4-diamine dihydrochloride (104 mg, 48%) as a white solid.

Workup

  1. filtrationfiltered
  2. additionpoured into saturated aqueous NaHCO3
  3. extractionThe aqueous layer was extracted with CHCl3 (three times)
  4. dry with materialThe combined organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by flash chromatography (NH-silica gel, 50% EtOAc in hexane)
  8. customto give a colorless oil
  9. stirringThe mixture was stirred at ambient temperature for 1 hr
  10. concentrationconcentrated
  11. stirringstirred at ambient tempareture for 1 hr
  12. filtrationThe solid was collected by filtration
  13. washwashed with Et20
  14. customdried under reduced pressure

Sources & evidence

ORD record
ord-427ad8c0503f4dd897582072924eb09f
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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