Chloroacetaldehyde → 4-(2-{5-[3-(3-Fluoro-phenyl)-2-oxo-imidazolidin-1-yl]-2-methyl-phenylamino}-oxazol-5-yl)-benzonitrile

HRID 244592Notes

Reaction equation

HRID 244592 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:22])=[C:6]([NH:8][C:9]2[O:10][C:11]([C:14]3[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=3)=[CH:12][N:13]=2)[CH:7]=1.Cl[CH2:24][CH:25]=O.[BH3-]C#N.[Na+].C([O-])(O)=O.[Na+].[F:36][C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([N:43]=[C:44]=[O:45])[CH:38]=1.CC(C)([O-])C.[K+]>C(#N)C.C1(C)C=CC=CC=1.O.C(OCC)(=O)C.C(O)(=O)C>[F:36][C:37]1[CH:38]=[C:39]([N:43]2[CH2:25][CH2:24][N:1]([C:2]3[CH:3]=[CH:4][C:5]([CH3:22])=[C:6]([NH:8][C:9]4[O:10][C:11]([C:14]5[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=5)=[CH:12][N:13]=4)[CH:7]=3)[C:44]2=[O:45])[CH:40]=[CH:41][CH:42]=1

Participants

12

Reactant 6

HCID 33ChloroacetaldehydeHCID 1230643-Fluorophenyl isocyanateHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 177573464-[2-(5-Amino-2-methyl-phenylamino)-oxazol-5-yl]-benzonitrileHCID 23665647Potassium tert-butoxide

Product 1

HCID 119653644-(2-{5-[3-(3-Fluoro-phenyl)-2-oxo-imidazolidin-1-yl]-2-methyl-phenylamino}-oxazol-5-yl)-benzonitrileYield 45%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-[2-(5-Amino-2-methyl-phenylamino)-oxazol-5-yl]-benzonitrile (558 mg, 2 mmol) and chloroacetaldehyde (50 wt. % in water, 628 mg, 4 mmol) in acetonitril (60 mL), was added at RT NaBH3CN (253 mg, 4 mmol) and dropwise acetic acid (0.4 mL). The mixture was stirred at room temperature 1 h. Ethyl acetate (50 mL) and saturated aqueous NaHCO3 (50 mL) were added. The organic layer was washed with brine (20 mL), dried over MgSO4 and concentrated to give a yellow solid. This was dissolved in toluene (40 mL) and treated with 1-Fluoro-3-isocyanato-benzene (274 mg, 2 mmol) at reflux for 2 h. After evaporation of solvent under reduced vacuum, the crude product was dissolved in isopropanol (60 mL) and treated with potassium tert-butoxide (1.8 g, 16 mmol) at RT for 5 h. Water (20 mL) was added, the organic layer was separated dried over MgSO4 and concentrated. The crude product was silica gel column chromatographed (dichloromethane/ethanol: 95/5) to give 408 mg (45%) of the title compound as a beige solid.

Workup

  1. washThe organic layer was washed with brine (20 mL)
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customto give a yellow solid
  5. temperatureat reflux for 2 h
  6. customAfter evaporation of solvent under reduced vacuum
  7. dissolutionthe crude product was dissolved in isopropanol (60 mL)
  8. customthe organic layer was separated
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated
  11. customchromatographed (dichloromethane/ethanol: 95/5)

Sources & evidence

ORD record
ord-edc51a882ed8418e8057a0815757bbe6
Source dataset
uspto-grants-2014_02
Patent number
US08658659B2

Reaction notes

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