1,4-Dioxane → 2-[5-Fluoro-1-[(2-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-nitro-4,6-pyrimidinediamine

HRID 1777802Notes

Reaction equation

HRID 1777802 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:10](I)=[N:9][N:8]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[F:19])[C:5]2=[N:6][CH:7]=1.O1CCOCC1.CCCC[Sn](CCCC)CCCC.CCCC[Sn](CCCC)CCCC.Cl[C:53]1[N:58]=[C:57]([NH2:59])[C:56]([N+:60]([O-:62])=[O:61])=[C:55]([NH2:63])[N:54]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[F:1][C:2]1[CH:3]=[C:4]2[C:10]([C:53]3[N:54]=[C:55]([NH2:63])[C:56]([N+:60]([O-:62])=[O:61])=[C:57]([NH2:59])[N:58]=3)=[N:9][N:8]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[F:19])[C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 6327815HexabutyldistannaneHCID 580656025-Fluoro-1-(2-fluorobenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridineHCID 59177864HCID 59177864, compound

Product 1

HCID 580656012-[5-Fluoro-1-[(2-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-nitro-4,6-pyrimidinediamine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

Under argon, 860 mg (2.32 mmol) of the compound from Example 6A were introduced into 1,4-dioxane (86 ml), and the reaction mixture was flushed with argon for 10 min. Then 3.51 ml (6.95 mmol) of hexabutylditin and 483 mg (2.55 mmol) of 2-chloro-5-nitropyrimidine-4,6-diamine (prepared by the method of Helvetica Chimica Acta (1951), 34, 835-40) were added. Subsequently 860 mg (0.744 mmol) of tetrakis(triphenylphosphine)palladium(0) were added and the reaction mixture was heated at reflux overnight. The mixture was then cooled to RT, water was added and the mixture was extracted twice with ethyl acetate. The collected organic phases were dried over sodium sulphate, filtered and concentrated. The residue was subjected to extractive stirring in ethyl acetate, and the solid was isolated by filtration and dried under high vacuum. This gave 355 mg (62% purity, 24% of theory) of the desired compound. The crude product was reacted without further purification.

Workup

  1. customthe reaction mixture was flushed with argon for 10 min
  2. additionwere added
  3. temperaturethe reaction mixture was heated
  4. temperatureat reflux overnight
  5. extractionthe mixture was extracted twice with ethyl acetate
  6. dry with materialThe collected organic phases were dried over sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customthe solid was isolated by filtration
  10. customdried under high vacuum
  11. customThe crude product was reacted without further purification

Sources & evidence

ORD record
ord-bf6fac9e3e4f41249f97a834e639bbed
Source dataset
uspto-grants-2016_02
Patent number
US09266885B2

Reaction notes

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