Cesium carbonate → HCID 11524375, compound

HRID 1455529Notes

Reaction equation

HRID 1455529 reaction equation
Br[C:2]1[C:10]2[CH:9]=[CH:8][C:7](=[O:11])[N:6]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[Cl:18])[C:5]=2[S:4][C:3]=1[C:19]#[N:20].[F:21][C:22]1[CH:28]=[CH:27][C:25]([NH2:26])=[CH:24][C:23]=1[CH3:29].C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>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]>[Cl:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[N:6]1[C:7](=[O:11])[CH:8]=[CH:9][C:10]2[C:2]([NH:26][C:25]3[CH:27]=[CH:28][C:22]([F:21])=[C:23]([CH3:29])[CH:24]=3)=[C:3]([C:19]#[N:20])[S:4][C:5]1=2

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 679814-Fluoro-m-toluidineHCID 634876Binap, (A+-)-2×HCID 66970806HCID 66970806, compound

Product 1

HCID 11524375HCID 11524375, compoundYield 28.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 1140TolueneSolvent

Procedure

A mixture of Example 13 (500 mg, 1.37 mmol), 4-fluoro-3-methylaniline (206 mg, 1.64 mmol), Cs2CO3 (625 mg, 1.92 mmol), BINAP (85 mg, 0.37 mmol, 10 mol %) and Pd2(dba)3 (63 mg, 0.0685 mmol, 5 mol %) in toluene was heated at reflux for 18 h. A second charge of BINAP (42 mg, 5 mol %) and tris(dibenzylideneacetone)dipalladium(0) (31.5 mg, 2.5 mol %) was added and the mixture heated at reflux for a further 4 days. The mixture was partitioned between DCM (100 mL) and H2O (50 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo. Purification by column chromatography (silica, 10% EtOAc in DCM) gave the title compound as an off-white solid (160 mg, 28%). δH (DMSO-d6) 9.39 (1H, s), 8.17 (1H, d, J 9.7 Hz), 7.87 (1H, dd, J 1.7, 7.9 Hz), 7.79 (1H, dd, J 2.1, 7.9 Hz), 7.75-7.66 (2H, m), 7.24-7.12 (3H, m), 6.71 (1H, d, J 9.7 Hz), 2.29 (3H, d, J 1.7 Hz). LCMS (ES+) RT 3.63 minutes, 410 (M+H)+.

Workup

  1. temperatureat reflux for 18 h
  2. additionwas added
  3. temperaturethe mixture heated
  4. temperatureat reflux for a further 4 days
  5. customThe mixture was partitioned between DCM (100 mL) and H2O (50 mL)
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customPurification by column chromatography (silica, 10% EtOAc in DCM)

Sources & evidence

ORD record
ord-ff3713cbaf8b446dbaace2070eb6cc85
Source dataset
uspto-grants-2009_01
Patent number
US07482452B2

Reaction notes

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