Nitrogen → N-(3-fluoro-4-(4-methylpiperazin-1-yl)phenyl)-1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-5-amine

HRID 715055Notes

Reaction equation

HRID 715055 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([CH3:11])=[N:9][N:8]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)[C:5]2=[N:6][CH:7]=1.[F:21][C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][C:28]=1[N:29]1[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]1)[NH2:25].N#N.C(O[K])(C)(C)C.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.C(Cl)(Cl)Cl.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]>[F:21][C:22]1[CH:23]=[C:24]([NH:25][C:2]2[CH:3]=[C:4]3[C:10]([CH3:11])=[N:9][N:8]([CH2:12][C:13]4[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=4)[C:5]3=[N:6][CH:7]=2)[CH:26]=[CH:27][C:28]=1[N:29]1[CH2:30][CH2:31][N:32]([CH3:35])[CH2:33][CH2:34]1

Participants

9

Reactant 5

HCID 947NitrogenHCID 634876Binap, (A+-)-HCID 27830553-Fluoro-4-(4-methylpiperazin-1-yl)anilineHCID 578563335-bromo-1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridineHCID 178418922HCID 178418922, compound

Product 1

HCID 70811059N-(3-fluoro-4-(4-methylpiperazin-1-yl)phenyl)-1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-5-amine

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6212ChloroformSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A stirred solution of 5-bromo-1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine (7) (100 mg, 0.301 mmol) and 3-fluoro-4-(4-methylpiperazin-1-yl)aniline (168) (77 mg, 0.33 mmol, 1.1 eq) in 1,4-dioxane (10 mL) was degassed and purged with N2 for 10 min. tert-BuOK (101 mg, 0.903 mmol, 3.0 eq) was added and the reaction mixture purged and degassed again. To this reaction mixture was added ±BINAP (8 mg, 0.00301 mmol, 0.01 eq) and Pd2(dba)3 (11 mg, 0.0012 mmol, 0.04 eq) and the resulting reaction was heated at 90° C. for 12 hrs in sealed tube condition. After completion of the reaction the contents were cooled and diluted with CHCl3 and filtered through Celite bed. The CHCl3 layer was completely distilled off to get the crude product. The crude was passed through 100-200 mesh silica gel, eluting the pure compound N-(3-fluoro-4-(4-methylpiperazin-1-yl)phenyl)-1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-5-amine 169 obtained with 6% MeOH in CH2Cl2 as an off-white colored solid in 40 mg quantity.

Workup

  1. additionwas added
  2. customthe reaction mixture purged
  3. customdegassed again
  4. customthe resulting reaction
  5. customAfter completion of the reaction the contents
  6. temperaturewere cooled
  7. filtrationfiltered through Celite bed
  8. distillationThe CHCl3 layer was completely distilled off
  9. customto get the crude product
  10. washeluting the pure compound N-(3-fluoro-4-(4-methylpiperazin-1-yl)phenyl)-1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-5-amine 169
  11. customobtained with 6% MeOH in CH2Cl2 as an off-white colored solid in 40 mg quantity

Sources & evidence

ORD record
ord-5f4f542052784662a6efaa514c495589
Source dataset
uspto-grants-2015_11
Patent number
US09187473B2

Reaction notes

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