Ammonia → HCID 178483088, compound

HRID 1984911Notes

Reaction equation

HRID 1984911 reaction equation
Br[C:2]1[CH:29]=[CH:28][C:5]([CH2:6][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)=[C:4]([O:30][C:31]([F:34])([F:33])[F:32])[CH:3]=1.[NH3:35].O.[ClH:37]>CCO.CCOC(C)=O.[Cu].Cl[Cu]>[ClH:37].[ClH:37].[ClH:37].[NH2:35][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][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)=[C:4]([O:30][C:31]([F:34])([F:33])[F:32])[CH:3]=1

Participants

9

Reactant 4

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 962WaterHCID 178483085HCID 178483085, compound

Product 1

HCID 178483088HCID 178483088, compoundYield 6%

Reagents, catalysts & solvents 4

HCID 23978CopperCatalystHCID 62652Cuprous chlorideCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of cis-N2-[4-(4-bromo-2-trifluoromethoxy-benzylamino)-cyclohexyl]-N4,N4-dimethyl-quinazoline-2,4-diamine obtained in step A of example 28 (1.5 g, 2.79 mmol) in EtOH (25 mL) were added copper powder (443 mg, 6.93 mmol), CuCl (690 mg, 2.79 mmol), and 28% aqueous NH3 (25 mL). The reaction mixture was stirred at reflux for 3.5 hr. The mixture was poured into water, and the aqueous layer was extracted with CHCl3 (three times). The combined organic layer was dried over MgSO4, filtered, concentrated, and purified by medium-pressure liquid 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. A solution of the residue in Et2O (15 mL) was stirred at ambient tempareture for 1 hr. The precipitate was collected by filtration, washed with Et2O, and dried under reduced pressure to give cis-N2-[4-(4-amino-2-trifluoromethoxy-benzylamino)-cyclohexyl]-N4,N4-dimethyl-quinazoline-2,4-diamine trihydrochloride (104 mg, 6%) as a white solid.

Workup

  1. temperatureat reflux for 3.5 hr
  2. extractionthe aqueous layer was extracted with CHCl3 (three times)
  3. dry with materialThe combined organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by medium-pressure liquid chromatography (NH-silica gel, 50% EtOAc in hexane)
  7. customto give a colorless oil
  8. stirringThe mixture was stirred at ambient temperature for 1 hr
  9. concentrationconcentrated
  10. stirringA solution of the residue in Et2O (15 mL) was stirred at ambient tempareture for 1 hr
  11. filtrationThe precipitate was collected by filtration
  12. washwashed with Et2O
  13. customdried under reduced pressure

Sources & evidence

ORD record
ord-7f2886d7633a4c93af1c87c12aa4cab8
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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