Cesium carbonate → HCID 178480728, compound

HRID 2236866Notes

Reaction equation

HRID 2236866 reaction equation
[F:1][C:2]1[C:7]([NH:8]/[CH:9]=[C:10]2\[C:11](=[O:22])[NH:12][C:13](=[O:21])[C:14]3[C:19]\2=[CH:18][C:17](I)=[CH:16][CH:15]=3)=[CH:6][CH:5]=[C:4]([N:23]2[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]2)[N:3]=1.[O:30]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31]1.C(=O)([O-])[O-].[Cs+].[Cs+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>CN(C)C=O.C(Cl)(Cl)Cl.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]>[F:1][C:2]1[C:7]([NH:8]/[CH:9]=[C:10]2\[C:11](=[O:22])[NH:12][C:13](=[O:21])[C:14]3[C:19]\2=[CH:18][C:17]([C:32]2[CH:33]=[CH:34][O:30][CH:31]=2)=[CH:16][CH:15]=3)=[CH:6][CH:5]=[C:4]([N:23]2[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]2)[N:3]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 2734358Furan-3-boronic acidHCID 178480735HCID 178480735, compound

Product 1

HCID 178480728HCID 178480728, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A suspension of (4Z)-4-({[2-fluoro-6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino}methylene)-6-iodoisoquinoline-1,3(2H,4H)-dione (0.10 g, 0.20 mmol), 3-furanboronic acid (55 mg, 0.50 mmol), tris(dibenzylideneacetone)dipalladium(0) (27 mg, 0.03 mmol) and cesium carbonate (0.13 g) in N,N-dimethylformamide (2 mL) is heated in a 120° C. oil bath for 10 minutes. Tri-tert-butylphosphine (20 mg/mL solution in N,N-dimethylformamide, 0.50 mL, 10 mg, 0.05 mmol) is added, and the mixture continued to stir in the oil bath for one hour. After cooling to room temperature, the reaction mixture is diluted with chloroform and washed with saturated aqueous sodium hydrogen carbonate solution. The organic layer is concentrated under reduced pressure and purified via reverse phase HPLC to provide (4Z)-4-({[2-fluoro-6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino}methylene)-6-(3-furyl)isoquinoline-1,3(2H,4H)-dione.3 trifluoroacetic acid salt (53 mg, 34%).

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with saturated aqueous sodium hydrogen carbonate solution
  3. concentrationThe organic layer is concentrated under reduced pressure
  4. custompurified via reverse phase HPLC

Sources & evidence

ORD record
ord-5bd5da9d064040d6a3c4fa4836f641b9
Source dataset
uspto-grants-2010_05
Patent number
US07713994B2

Reaction notes

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