Sodium Bicarbonate → 6-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-3-nitropyridin-2-amine

HRID 510043Notes

Reaction equation

HRID 510043 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])=[CH:48][CH:47]=1.C(=O)([O-])O.[Na+]>CN(C)C=O>[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])=[CH:48][CH:47]=2)=[N:6]1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 27240356-Chloro-3-nitropyridin-2-ylamineHCID 6327815HexabutyldistannaneHCID 574158911-(2-fluorobenzyl)-3-iodo-1H-pyrazolo(3,4-b)pyridine

Product 1

HCID 666135626-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-3-nitropyridin-2-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

200 mg (0.57 mmol) of the compound from example 33A were initially charged in dimethylformamide (5.3 ml) under argon, then 0.43 ml (0.85 mmol) of hexabutylditin and 160 mg (0.92 mmol) of 6-chloro-3-nitropyridin-2-amine were added, and the reaction mixture was purged with argon for 10 min. Subsequently, 231 mg (0.28 mmol) of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane complex (1:1) were added and the reaction mixture was stirred at 110° C. overnight. The mixture was then cooled to RT, saturated aqueous sodium hydrogencarbonate solution was added and the mixture was extracted three times with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated. The residue was extracted by stirring in dichloromethane/methanol (1:1), and the solids were filtered off and dried under high vacuum. This gave 95 mg (54% purity, 15% of theory) of the title compound. The filtrate was chromatographed on silica gel (eluent: 20:1 cyclohexane/ethyl acetate) and the product fractions were concentrated. The residue was suspended in methanol, the solids were filtered off and drying under high vacuum afforded a further 30 mg (15% of theory) of the title compound in solid form. The fractions were combined and converted without further purification (purity approx. 60%).

Workup

  1. customthe reaction mixture was purged with argon for 10 min
  2. additionSubsequently, 231 mg (0.28 mmol) of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichloromethane complex (1:1) were added
  3. temperatureThe mixture was then cooled to RT
  4. extractionthe mixture was extracted three times with ethyl acetate
  5. dry with materialThe combined organic phases were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. extractionThe residue was extracted
  9. stirringby stirring in dichloromethane/methanol (1:1)
  10. filtrationthe solids were filtered off
  11. customdried under high vacuum
  12. customThe filtrate was chromatographed on silica gel (eluent: 20:1 cyclohexane/ethyl acetate)
  13. concentrationthe product fractions were concentrated
  14. filtrationthe solids were filtered off
  15. customdrying under high vacuum

Sources & evidence

ORD record
ord-bd25fc1a421642eba161db1eefdc754d
Source dataset
uspto-grants-2015_08
Patent number
US09096592B2

Reaction notes

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