Hydrochloric Acid → HCID 178483083, compound

HRID 1984903Notes

Reaction equation

HRID 1984903 reaction equation
C1OCCOCCOCCOCCOCCOC1.[Br:19][C:20]1[CH:25]=[CH:24][C:23](I)=[C:22]([O:27][C:28]([F:31])([F:30])[F:29])[CH:21]=1.[NH2:32][C@@H:33]1[CH2:38][CH2:37][C@H:36]([NH:39][C:40]2[N:49]=[C:48]([N:50]([CH2:53]C)[CH2:51]C)[C:47]3[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=3)[N:41]=2)[CH2:35][CH2:34]1.CC(C)([O-])C.[Na+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[ClH:107]>CCOCC.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1COCC1>[ClH:107].[ClH:107].[Br:19][C:20]1[CH:25]=[CH:24][C:23]([NH:32][C@@H:33]2[CH2:34][CH2:35][C@H:36]([NH:39][C:40]3[N:49]=[C:48]([N:50]([CH3:53])[CH3:51])[C:47]4[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=4)[N:41]=3)[CH2:37][CH2:38]2)=[C:22]([O:27][C:28]([F:31])([F:30])[F:29])[CH:21]=1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 2855718-Crown-6HCID 634876Binap, (A+-)-HCID 27364224-Bromo-2-(trifluoromethoxy)iodobenzeneHCID 23676156Sodium t-butoxideHCID 178463885HCID 178463885, compound

Product 1

HCID 178483083HCID 178483083, compoundYield 18%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a glass flask were added 18-crown-6 (647 mg, 2.45 mmol), 4-Bromo-1-iodo-2-trifluoromethoxy-benzene (770 mg, 2.10 mmol), cis-N2-(4-amino-cyclohexyl)-N4,N4-dimethyl-quinazoline-2,4-diamine obtained in step C of example 9 (500 mg, 1.75 mmol), sodium tert-butoxide (235 mg, 2.45 mmol), tris(dibenzylideneacetone)dipalladium (160 mg, 0.175 mmol), (R)-(+)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (160 mg, 0.175 mmol) and THF (3.5 mL). The reaction mixture was stirred at reflux 18 hr. The mixture was filtered through a pad of celite, concentrated, and purified by flash chromatography (NH-silica gel, 33% EtOAc in hexane) to give a pale yellow oil. To a solution of above oil in Et2O (2 mL) was added 4 M hydrogen chloride in EtOAc (0.3 mL). The mixture was stirred at ambient temperature for 30 min and concentrated. A solution of the residue in Et2O (2 mL) was stirred at ambient tempareture for 15 min. The precipitate was collected by filtration, washed with Et2O, and dried under reduced pressure to give cis-N2-[4-(4-bromo-2-trifluoromethoxy-phenylamino)-cyclohexyl]-N4,N4-dimethyl-quinazoline-2,4-diamine dihydrochloride (189 mg, 18%) as a white solid.

Workup

  1. temperatureat reflux 18 hr
  2. filtrationThe mixture was filtered through a pad of celite
  3. concentrationconcentrated
  4. custompurified by flash chromatography (NH-silica gel, 33% EtOAc in hexane)
  5. customto give a pale yellow oil
  6. stirringThe mixture was stirred at ambient temperature for 30 min
  7. concentrationconcentrated
  8. stirringA solution of the residue in Et2O (2 mL) was stirred at ambient tempareture for 15 min
  9. filtrationThe precipitate was collected by filtration
  10. washwashed with Et2O
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-163edc018bd04e6282360fe77f26dcbb
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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