Acetic Acid → HCID 178483091, compound

HRID 1984907Notes

Reaction equation

HRID 1984907 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][CH2:32][CH2:33][CH:34]=O)=[C:27]([O:36][C:37]([F:40])([F:39])[F:38])[CH:26]=1.C(O)(=O)C.[BH3-]C#N.[Na+].[ClH:49]>CO.CCOC(C)=O>[ClH:49].[ClH:49].[Br:24][C:25]1[CH:30]=[CH:29][C:28]([CH2:31][CH2:32][CH2:33][CH2:34][NH:1][C@@H:2]2[CH2:7][CH2:6][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)[CH2:4][CH2:3]2)=[C:27]([O:36][C:37]([F:38])([F:39])[F:40])[CH:26]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 5003444Sodium cyanoborohydrideHCID 866108684-(4-Bromo-2-trifluoromethoxy-phenyl)-butyraldehydeHCID 178463885HCID 178463885, compound

Product 1

HCID 178483091HCID 178483091, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 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 (240 mg, 0.84 mmol) in MeOH (3 mL) were added 4-(4-bromo-2-trifluoromethoxy-phenyl)-butyraldehyde (262 mg, 0.84 mmol), acetic acid (79 mg, 1.26 mmol), and NaBH3CN (79 mg, 1.26 mmol). The reaction mixture was stirred at ambient temperature for 8 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 medium-pressure liquid chromatography (NH-silica gel, 50% EtOAc in hexane) to give a pale yellow solid. To a solution of above solid in EtOAc (2 mL) was added 4 M hydrogen chloride in EtOAc (10 mL). The mixture was stirred at ambient temperature for 1 hr and concentrated. A solution of the residue in Et2O (20 mL) was stirred at ambient tempareture for 1 hr. The solid was collected by filtration, washed with Et2O, and dried under reduced pressure to give cis-N2-{4-[4-(4-bromo-2-trifluoromethoxy-phenyl)-butylamino]-cyclohexyl}-N4,N4-dimethyl-quinazoline-2,4-diamine dihydrochloride (220 mg, 40%) 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 medium-pressure liquid chromatography (NH-silica gel, 50% EtOAc in hexane)
  7. customto give a pale yellow solid
  8. stirringThe mixture was stirred at ambient temperature for 1 hr
  9. concentrationconcentrated
  10. stirringA solution of the residue in Et2O (20 mL) was stirred at ambient tempareture for 1 hr
  11. filtrationThe solid was collected by filtration
  12. washwashed with Et2O
  13. customdried under reduced pressure

Sources & evidence

ORD record
ord-f2c02e8658ac496cadf41dddc35c177f
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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