Binap, (A+-)- → 2-Butyl-5-(4-phenylpyridin-3-ylamino)isoindolin-1-one

HRID 1878632

Reaction equation

HRID 1878632 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH2:60][C:61]1[CH:62]=[C:63]2[C:67](=[CH:68][CH:69]=1)[C:66](=[O:70])[N:65]([CH2:71][CH2:72][CH2:73][CH3:74])[CH2:64]2.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C.O>[CH2:71]([N:65]1[CH2:64][C:63]2[C:67](=[CH:68][CH:69]=[C:61]([NH:60][C:2]3[CH:3]=[N:4][CH:5]=[CH:6][C:7]=3[C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH:62]=2)[C:66]1=[O:70])[CH2:72][CH2:73][CH3:74]

Participants

9

Reactant 4

HCID 634876Binap, (A+-)-HCID 27629283-Bromo-4-phenylpyridineHCID 23676156Sodium t-butoxideHCID 674320655-Amino-2-butyl-2,3-dihydro-1H-isoindol-1-one

Product 1

HCID 534771292-Butyl-5-(4-phenylpyridin-3-ylamino)isoindolin-1-oneYield 46%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
120 °C

Procedure

3-Bromo-4-phenylpyridine (125 mg, 0.534 mmol) was added to a suspension of 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) (33 mg, 0.053 mmol) and tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3) (49 mg, 0.053 mmol) in toluene (5 mL). 5-Amino-2-butylisoindolin-1-one (120 mg, 0.587 mmol) and sodium tert-butoxide (128 mg, 1.335 mmol) were added and the mixture was stirred and heated in the microwave (120° C., 300 W, 75 min). Water and ethyl acetate were added, the organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water and dried over MgSO4. Purification by flash chromatography (dichloromethane/methanol, gradient 1-5% methanol) provided 2-butyl-5-(4-phenylpyridin-3-ylamino)isoindolin-1-one (56 mg, 46%). ESI-MS [M+H]+=358.2.

Workup

  1. customthe organic layer was separated
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. washThe combined organic layers were washed with water
  4. dry with materialdried over MgSO4
  5. customPurification by flash chromatography (dichloromethane/methanol, gradient 1-5% methanol)

Sources & evidence

ORD record
ord-91b69fd51ec14050860577b9e1cd9ae3
Source dataset
uspto-grants-2012_11
Patent number
US08314120B2

Linked notes

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