Cesium carbonate → [2-(2,6-Dichloro-4-vinylphenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-yl]-(6-methylpyrimidin-4-yl)amine

HRID 626805Notes

Reaction equation

HRID 626805 reaction equation
Br[C:2]1[C:7]2=[CH:8][N:9]([C:11]3[C:16]([Cl:17])=[CH:15][C:14]([CH:18]=[CH2:19])=[CH:13][C:12]=3[Cl:20])[N:10]=[C:6]2[C:5]([F:21])=[CH:4][N:3]=1.[CH3:22][C:23]1[N:28]=[CH:27][N:26]=[C:25]([NH2:29])[CH:24]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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:20][C:12]1[CH:13]=[C:14]([CH:18]=[CH2:19])[CH:15]=[C:16]([Cl:17])[C:11]=1[N:9]1[CH:8]=[C:7]2[C:2]([NH:29][C:25]3[CH:24]=[C:23]([CH3:22])[N:28]=[CH:27][N:26]=3)=[N:3][CH:4]=[C:5]([F:21])[C:6]2=[N:10]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 5728526-Methylpyrimidin-4-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866970824-Bromo-2-(2,6-dichloro-4-vinylphenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine

Product 1

HCID 69671745[2-(2,6-Dichloro-4-vinylphenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-yl]-(6-methylpyrimidin-4-yl)amineYield 62.4%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

A mixture of 4-bromo-2-(2,6-dichloro-4-vinylphenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine (295 mg, 0.76 mmol), 6-methylpyrimidin-4-ylamine (99 mg, 0.91 mmol), Pd2(dba)3 (17 mg, 0.019 mmol), Xantphos (44 mg, 0.076 mmol) and cesium carbonate (495 mg, 1.52 mmol) in dioxane (8.0 mL) was de-gassed and purged with nitrogen and the reaction mixture was heated at 80° C. in a sealed vial overnight. The resultant mixture was allowed to cool to room temperature, before being partitioned between ethyl acetate and water. The layers were separated and the organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (70-80% ethyl acetate in cyclohexane) to afford the title compound as a beige solid (197 mg, 62% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.69 (s, 1H), 9.24 (d, J=2.6 Hz, 1H), 8.67 (d, J=1.2 Hz, 1H), 8.36 (s, 1H), 7.98-7.93 (m, 3H), 6.88-6.78 (m, 1H), 6.22 (d, J=17.6 Hz, 1H), 5.58 (d, J=11.0 Hz, 1H), 2.43 (s, 3H).

Workup

  1. customwas de-gassed
  2. custompurged with nitrogen
  3. temperatureto cool to room temperature
  4. custombefore being partitioned between ethyl acetate and water
  5. customThe layers were separated
  6. washthe organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel flash chromatography (70-80% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-a05e6dab0efc402bbe0a1c278b20a4b1
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

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