4-Amino-2-chloro-6-methyl-5-nitropyrimidine → 2-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6-methyl-5-nitropyrimidin-4-amine

HRID 510051Notes

Reaction equation

HRID 510051 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.Cl[C:46]1[N:51]=[C:50]([NH2:52])[C:49]([N+:53]([O-:55])=[O:54])=[C:48]([CH3:56])[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:46]2[N:51]=[C:50]([NH2:52])[C:49]([N+:53]([O-:55])=[O:54])=[C:48]([CH3:56])[N:47]=2)=[N:6]1

Participants

6

Reactant 3

HCID 2274594-Amino-2-chloro-6-methyl-5-nitropyrimidineHCID 6327815HexabutyldistannaneHCID 574158911-(2-fluorobenzyl)-3-iodo-1H-pyrazolo(3,4-b)pyridine

Product 1

HCID 666140422-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6-methyl-5-nitropyrimidin-4-amine

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

Under argon, 1.50 g (4.25 mmol) of the compound from Example 33A were initially charged in 1,4-dioxane (37.5 ml), and the reaction mixture was purged with argon for 10 min. Thereafter, 3.22 ml (6.37 mmol) of hexabutylditin and 881 mg (4.67 mmol) of 2-chloro-6-methyl-5-nitropyrimidin-4-amine were added. Subsequently, 1.49 g (2.12 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 washed through with methanol. The solids formed were filtered off and discarded. The remaining filtrate was concentrated, ethyl acetate was added, and the solids formed were filtered off and dried under high vacuum. This gave 640 mg (69% purity, 27% 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. washthe filtrate was washed through with methanol
  6. customThe solids formed
  7. filtrationwere filtered off
  8. concentrationThe remaining filtrate was concentrated
  9. additionethyl acetate was added
  10. customthe solids formed
  11. filtrationwere filtered off
  12. customdried under high vacuum
  13. customThe crude product was converted further without further purification

Sources & evidence

ORD record
ord-ff6d2f85077f451e8b5d0a721c5f9af4
Source dataset
uspto-grants-2015_08
Patent number
US09096592B2

Reaction notes

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