Cesium carbonate → HCID 66610440, compound

HRID 473219Notes

Reaction equation

HRID 473219 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]([F:21])([F:20])[C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=1)[N:8]=[C:7]2[S:22][CH3:23].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.[CH3:66][S:67]([NH2:70])(=[O:69])=[O:68].C([O-])([O-])=O.[Cs+].[Cs+]>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].O1CCOCC1>[F:20][C:12]([F:21])([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=1)[C:9]1[N:8]=[C:7]([S:22][CH3:23])[C:6]2[C:11](=[C:2]([NH:70][S:67]([CH3:66])(=[O:69])=[O:68])[CH:3]=[CH:4][CH:5]=2)[N:10]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 72879MethanesulfonamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 666094698-Bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline

Product 1

HCID 66610440HCID 66610440, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 8-bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline from Example 35 step B (250 mg, 0.625 mmol), tris(dibenzylideneacetone)dipalladium (57 mg, 0.063 mmol), 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (108 mg, 0.187 mmol), methanesulfonamide (83 mg, 0.87 mmol) and Cs2CO3 (284 mg, 0.87 mmol) was added dioxane (5 mL). The reaction vessel was evacuated and flushed with argon (3×), and the mixture was heated at 100° C. overnight. The mixture was allowed to cool and was then diluted with DCM and concentrated under reduced pressure onto Celite. The residue was purified by silica gel flash chromatography eluting with 10-100% EtOAc/hexanes to afford impure N-(2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazolin-8-yl)methanesulfonamide (220 mg, 85%). LC-MS (ESI) m/z 415 (M+H)+.

Workup

  1. customThe reaction vessel was evacuated
  2. customflushed with argon (3×)
  3. temperatureto cool
  4. additionwas then diluted with DCM
  5. concentrationconcentrated under reduced pressure onto Celite
  6. customThe residue was purified by silica gel flash chromatography
  7. washeluting with 10-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-f0c4deb73b274b87af10d05b0daa887c
Source dataset
uspto-grants-2014_01
Patent number
US08633207B2

Reaction notes

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