5-Bromopyrazine-2,3-diamine → 5-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrazine-2,3-diamine

HRID 510050Notes

Reaction equation

HRID 510050 reaction equation
[F:1][C:2]1[CH:18]=[CH:17][CH:16]=[CH:15][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7](I)=[N:6]1.CCCC[Sn](CCCC)CCCC.CCCC[Sn](CCCC)CCCC.[NH2:45][C:46]1[C:51]([NH2:52])=[N:50][C:49](Br)=[CH:48][N:47]=1>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:1][C:2]1[CH:18]=[CH:17][CH:16]=[CH:15][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:48]2[N:47]=[C:46]([NH2:45])[C:51]([NH2:52])=[N:50][CH:49]=2)=[N:6]1

Participants

6

Reactant 3

HCID 27718575-Bromopyrazine-2,3-diamineHCID 6327815HexabutyldistannaneHCID 574158911-(2-fluorobenzyl)-3-iodo-1H-pyrazolo(3,4-b)pyridine

Product 1

HCID 666143385-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrazine-2,3-diamine

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

Under argon, 425 mg (1.20 mmol) of the compound from Example 33A were initially charged in 1,4-dioxane (11 ml), and the reaction mixture was purged with argon for 10 min. Thereafter, 0.91 ml (1.80 mmol) of hexabutylditin and 250 mg (1.32 mmol) of 2,3-diamino-5-bromopyrazine were added. Subsequently, 422 mg (0.60 mmol) of bis(triphenylphosphine)palladium(II) chloride were added and the reaction mixture was heated to reflux overnight. Thereafter, the mixture was cooled to RT and filtered through Celite, and the filtrate was concentrated. The residue was admixed with methanol, and the solids were filtered off and discarded. The filtrate was taken up in methanol-dichloromethane, absorbed onto diatomaceous earth and purified on silica gel (eluent: cyclohexane-ethyl acetate 2:1, 1:1). This gave 151 mg (31% purity, 11% of theory) of the title compound. The crude product was converted further without further purification.

Workup

  1. customthe reaction mixture was purged with argon for 10 min
  2. temperaturethe reaction mixture was heated
  3. temperatureto reflux overnight
  4. filtrationfiltered through Celite
  5. concentrationthe filtrate was concentrated
  6. filtrationthe solids were filtered off
  7. customabsorbed onto diatomaceous earth
  8. custompurified on silica gel (eluent: cyclohexane-ethyl acetate 2:1, 1:1)
  9. customThe crude product was converted further without further purification

Sources & evidence

ORD record
ord-819c6b4e5b8547bd97d93575c16236a6
Source dataset
uspto-grants-2015_08
Patent number
US09096592B2

Reaction notes

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