Acetic Acid → HCID 178483089, compound

HRID 1984900Notes

Reaction equation

HRID 1984900 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]2[N:18]=[C:17]([N:19]([CH2:22]C)[CH2:20]C)[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=2)[CH2:4][CH2:3]1.[Br:24][C:25]1[CH:30]=[CH:29][C:28]([CH2:31][CH:32]=O)=[C:27]([O:34][C:35]([F:38])([F:37])[F:36])[CH:26]=1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[ClH:57]>C(Cl)Cl.CCOC(C)=O>[ClH:57].[ClH:57].[Br:24][C:25]1[CH:30]=[CH:29][C:28]([CH2:31][CH2:32][NH:1][C@@H:2]2[CH2:3][CH2:4][C@H:5]([NH:8][C:9]3[N:18]=[C:17]([N:19]([CH3:20])[CH3:22])[C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[N:10]=3)[CH2:6][CH2:7]2)=[C:27]([O:34][C:35]([F:36])([F:37])[F:38])[CH:26]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 5049666Sodium triacetoxyborohydrideHCID 86600516(4-Bromo-2-trifluoromethoxy-phenyl)-acetaldehydeHCID 178463885HCID 178463885, compound

Product 1

HCID 178483089HCID 178483089, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a suspension of cis-N2-(4-amino-cyclohexyl)-N4,N4-dimethyl-quinazoline-2,4-diamine obtained in step C of example 9 (300 mg, 1.05 mmol) in CH2Cl2 (3 mL) were added (4-bromo-2-trifluoromethoxy-phenyl)-acetaldehyde (357 mg, 1.26 mmol), AcOH (76 mg, 1.26 mmol), and NaBH(OAc)3 (334 mg, 1.57 mmol). The reaction mixture was stirred at ambient temperature for 4.5 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, 50% EtOAc in hexane) to give a pale yellow solid. To a solution of above solid in EtOAc (0.8 mL) was added 4 M hydrogen chloride in EtOAc (0.25 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 30 min. The precipitate was collected by filtration, washed with Et2O, and dried under reduced pressure to give cis-N2-{4-[2-(4-bromo-2-trifluoromethoxy-phenyl)-ethylamino]-cyclohexyl}-N4,N4-dimethyl-quinazoline-2,4-diamine dihydrochloride (161 mg, 25%) as a white solid.

Workup

  1. customThe reaction was quenched with saturated aqueous NaHCO3 The aqueous layer
  2. extractionwas extracted with CHCl3 (three times)
  3. dry with materialThe combined organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by flash chromatography (NH-silica gel, 50% EtOAc in hexane)
  7. customto give a pale yellow solid
  8. stirringThe mixture was stirred at ambient temperature for 30 min
  9. concentrationconcentrated
  10. stirringA solution of the residue in Et2O (2 mL) was stirred at ambient tempareture for 30 min
  11. filtrationThe precipitate was collected by filtration
  12. washwashed with Et2O
  13. customdried under reduced pressure

Sources & evidence

ORD record
ord-6cf12d26355049f3bed5189c30e12f8d
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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