3-Methoxyaniline → (RS)-4-(4-Methoxy-phenyl)-4-[3-(3-methoxy-phenylamino)-phenyl]-4,5-dihydro-oxazol-2-ylamine

HRID 1668760Notes

Reaction equation

HRID 1668760 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[CH2:12][O:11][C:10]([NH2:13])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C(CCC)=CC(CCC)=CC=1CCC)(C)(C)C.[CH3:58][O:59][C:60]1[CH:61]=[C:62]([CH:64]=[CH:65][CH:66]=1)[NH2:63]>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].C(OCC)(=O)C.O.C1(C)C=CC=CC=1>[CH3:21][O:20][C:17]1[CH:18]=[CH:19][C:14]([C:8]2([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([NH:63][C:62]4[CH:64]=[CH:65][CH:66]=[C:60]([O:59][CH3:58])[CH:61]=4)[CH:3]=3)[CH2:12][O:11][C:10]([NH2:13])=[N:9]2)=[CH:15][CH:16]=1

Participants

9

Reactant 4

HCID 108243-MethoxyanilineHCID 23676156Sodium t-butoxideHCID 57825178HCID 57825178, compoundHCID 67346612HCID 67346612, compound

Product 1

HCID 57825177(RS)-4-(4-Methoxy-phenyl)-4-[3-(3-methoxy-phenylamino)-phenyl]-4,5-dihydro-oxazol-2-ylamine

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A microwave tube was charged with (RS)-4-(3-bromo-phenyl)-4-(4-methoxy-phenyl)-4,5-dihydro-oxazol-2-ylamine (Building Block C, 100 mg, 0.288 mmol), sodium tert-butoxide (55 mg, 0.58 mmol), 2-di-t-butylphosphino-2′,4′,6′-tri-1-propyl-1,1′biphenyl (11 mg, 0.028 mmol), tris(dibenzylideneacetone)dipalladium (7 mg, 0.008 mmol) and 3-methoxyaniline (71 mg, 0.576 mmol). After three vacuum-nitrogen cycles, toluene was introduced (0.7 mL), the tube was scaled and stirred at 100° C. for 16 hours. After cooling to room temperature, water (1 mL) and ethyl acetate (1 mL) were added. The organic fraction of the reaction mixture was placed on an SCX column. This was then washed with dichloromethane/methanol. The desired product was obtained by eluting with 2 M ammonia in methanol. Fractions containing the compound were combined and the product purified further using preparative HPLC to yield 35 mg (31% yield) of the title compound as a white solid.

Workup

  1. temperatureAfter cooling to room temperature
  2. washThis was then washed with dichloromethane/methanol

Sources & evidence

ORD record
ord-54873b2250e6422aafb5b01efb8d70e9
Source dataset
uspto-grants-2011_08
Patent number
US07989449B2

Reaction notes

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