Sodium Carbonate → N-[4-Methyl-3-(3-methyl-1,2-benzisoxazol-6-yl)phenyl]-2-pyrrolidin-1-ylisonicotinamide

HRID 1988912Notes

Reaction equation

HRID 1988912 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]2[C:6]([CH3:9])=[N:7][O:8][C:4]=2[CH:3]=1.[CH3:12][C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:32])[C:21]2[CH:26]=[CH:25][N:24]=[C:23]([N:27]3[CH2:31][CH2:30][CH2:29][CH2:28]3)[CH:22]=2)=[CH:15][C:14]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC>[CH3:12][C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:32])[C:21]2[CH:26]=[CH:25][N:24]=[C:23]([N:27]3[CH2:31][CH2:30][CH2:29][CH2:28]3)[CH:22]=2)=[CH:15][C:14]=1[C:2]1[CH:11]=[CH:10][C:5]2[C:6]([CH3:9])=[N:7][O:8][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 11258289N-[4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]-2-pyrrolidin-1-yl-isonicotinamide2×HCID 124113226-Bromo-3-methyl-1,2-benzoxazole

Product 1

HCID 10364356N-[4-Methyl-3-(3-methyl-1,2-benzisoxazol-6-yl)phenyl]-2-pyrrolidin-1-ylisonicotinamideYield 36.9%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 6-bromo-3-methyl-1,2-benzisoxazole (11 mg), N-[4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-2-pyrrolidin-1-yl-isonicotinamide (Intermediate 13, 15 mg) and aqueous sodium carbonate (0.5M, 0.25 ml) in anhydrous DME (1 ml) was degassed then stirred under nitrogen. A solution of tetrakis(triphenylphosphine)palladium(0) (2.5 mg) in DME (0.25 ml) was added and the mixture was stirred at 80° for 16 h. The solvent was removed under vacuum and the residue was partitioned between dichloromethane and water. The organic layer was separated using a hydrophobic filter, the solvent was evaporated and the residue was purified by column chromatography on silica, eluting with a cyclohexane-ethyl acetate gradient to give the title compound as an oil (5.6 mg).

Workup

  1. customwas degassed
  2. additionA solution of tetrakis(triphenylphosphine)palladium(0) (2.5 mg) in DME (0.25 ml) was added
  3. stirringthe mixture was stirred at 80° for 16 h
  4. customThe solvent was removed under vacuum
  5. customthe residue was partitioned between dichloromethane and water
  6. customThe organic layer was separated
  7. customthe solvent was evaporated
  8. customthe residue was purified by column chromatography on silica
  9. washeluting with a cyclohexane-ethyl acetate gradient

Sources & evidence

ORD record
ord-f9307f2e331f4519a496d917cb278383
Source dataset
uspto-grants-2010_01
Patent number
US07642276B2

Reaction notes

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