4-Amino-1-methylpiperidine → N-(3-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)phenyl)-1-methylpiperidin-4-amine

HRID 1629923Notes

Reaction equation

HRID 1629923 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]3[C:16]([CH3:17])=[N:15][N:14]([CH2:18][C:19]4[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=4)[C:11]3=[N:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:27][N:28]1[CH2:33][CH2:32][CH:31]([NH2:34])[CH2:30][CH2:29]1.C(O[K])(C)(C)C>C(O)(C)(C)C.O1CCOCC1.O.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]>[CH3:26][O:25][C:22]1[CH:23]=[CH:24][C:19]([CH2:18][N:14]2[C:11]3=[N:12][CH:13]=[C:8]([C:4]4[CH:3]=[C:2]([NH:34][CH:31]5[CH2:32][CH2:33][N:28]([CH3:27])[CH2:29][CH2:30]5)[CH:7]=[CH:6][CH:5]=4)[CH:9]=[C:10]3[C:16]([CH3:17])=[N:15]2)=[CH:20][CH:21]=1

Participants

8

Reactant 3

HCID 27375314-Amino-1-methylpiperidineHCID 683885505-(3-chlorophenyl)-1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridineHCID 178418922HCID 178418922, compound

Product 1

HCID 68385403N-(3-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)phenyl)-1-methylpiperidin-4-amineYield 41.3%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6386tert-ButanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 5-(3-chlorophenyl)-1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine (96) (50 mg, 0.137 mmol) in tert-BuOH (4 mL), 1,4 dioxane (6 mL) was added 1-methylpiperidin-4-amine (16) (14 mg, 0.23 mmol, 0.9 eq) and tert-BuOK (38 mg, 0.344 mmol, 2.5 eq). The resulting reaction mixture was degassed, purged with N2 for 10 min and Pd2(dba)3 (5 mg, 0.00549 mmol, 0.04 eq) and tertButyl X-phos (0.08 eq) was added, the mixture was degassed and purged with nitrogen for 15 min. The reaction mixture was stirred overnight at 80° C. under sealed condition for 16 h. After completion of the reaction the reaction mass was diluted with water and extracted with ethyl acetate. The organic layer was dried over sodium sulphate and solvent completely distilled off to get the crude. The crude was passed through 100-200 mesh silica gel. Eluting the pure compound at 5% MeOH/CHCl3 gave 25 mg of N-(3-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)phenyl)-1-methylpiperidin-4-amine 97.

Workup

  1. customThe resulting reaction mixture
  2. customwas degassed
  3. custompurged with N2 for 10 min
  4. customthe mixture was degassed
  5. custompurged with nitrogen for 15 min
  6. customunder sealed condition for 16 h
  7. customAfter completion of the reaction the reaction mass
  8. extractionextracted with ethyl acetate
  9. dry with materialThe organic layer was dried over sodium sulphate and solvent
  10. distillationcompletely distilled off
  11. customto get the crude
  12. washEluting the pure compound at 5% MeOH/CHCl3

Sources & evidence

ORD record
ord-98d2963ab2fa4d22a21e29aab6e510db
Source dataset
uspto-grants-2014_07
Patent number
US08791112B2

Reaction notes

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