Ethyl Acetate → 4-Fluoro-1-(5-methoxy-4,6-dimethylpyridin-2-yl)-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-3-amine

HRID 1662263Notes

Reaction equation

HRID 1662263 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2([C:19]3[CH:24]=[C:23]([CH3:25])[C:22]([O:26][CH3:27])=[C:21]([CH3:28])[N:20]=3)[C:16]3[C:11](=[C:12]([F:17])[CH:13]=[CH:14][CH:15]=3)[C:10]([NH2:18])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[N:29]1[CH:34]=[C:33](B(O)O)[CH:32]=[N:31][CH:30]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CCOC(C)=O>COCCOC.CCO.O.[Cl-].[Na+].O.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe].O>[F:17][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:11]=1[C:10]([NH2:18])=[N:9][C:8]2([C:19]1[CH:24]=[C:23]([CH3:25])[C:22]([O:26][CH3:27])=[C:21]([CH3:28])[N:20]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([C:33]2[CH:34]=[N:29][CH:30]=[N:31][CH:32]=2)[CH:3]=1

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 585795341-(3-Bromophenyl)-4-fluoro-1-(5-methoxy-4,6-dimethylpyridin-2-yl)-1H-isoindol-3-amine

Product 1

HCID 462027434-Fluoro-1-(5-methoxy-4,6-dimethylpyridin-2-yl)-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-3-amineYield 17%

Reagents, catalysts & solvents 4

HCID 53485975CID 53485975CatalystHCID 962WaterSolventHCID 57417360Sodium chloride; waterSolventHCID 86587095Dimethoxyethane ethanol waterSolvent

Procedure

1-(3-Bromophenyl)-4-fluoro-1-(5-methoxy-4,6-dimethylpyridin-2-yl)-1H-isoindol-3-amine (272 mg, 0.62 mmol), pyrimidin-5-ylboronic acid (92 mg, 0.74 mmol), cesium carbonate (604 mg, 1.85 mmol) and dichloro[1,1′-bis (diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (50.4 mg, 0.06 mmol) were dissolved in DME:EtOH:water (6:3:1) (5 mL) and irradiated in a microwave oven for 20 min at 150° C. EtOAc, water and brine were added and the organic phase was collected, dried (Na2SO4) and filtered. The solvent was removed under reduced pressure and the residue was purified by preparative HPLC to afford 45 mg (17%) of the title compound.

Workup

  1. customirradiated in a microwave oven for 20 min at 150° C
  2. customthe organic phase was collected
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customThe solvent was removed under reduced pressure
  6. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-0d0c4774c20a4a5db87b6a5563a1ff12
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

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