Dimethylamine → 3-{(dimethylamino)methyl}-4-{4-iodo-3-isopropyl-1H-pyrazolo[3,4-b]pyridin-1-yl}benzonitrile

HRID 921567Notes

Reaction equation

HRID 921567 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[N:11]1[C:15]2=[N:16][CH:17]=[CH:18][C:19]([I:20])=[C:14]2[C:13]([CH:21]([CH3:23])[CH3:22])=[N:12]1)[C:6]#[N:7])=O.[CH3:24][NH:25][CH3:26]>C(O)(=O)C.CO>[CH3:24][N:25]([CH2:1][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[N:11]1[C:15]2=[N:16][CH:17]=[CH:18][C:19]([I:20])=[C:14]2[C:13]([CH:21]([CH3:23])[CH3:22])=[N:12]1)[C:6]#[N:7])[CH3:26]

Participants

5

Reactant 2

HCID 674DimethylamineHCID 866646033-Formyl-4-{4-iodo-3-isopropyl-1H-pyrazolo[3,4-b]pyridin-1-yl}benzonitrile

Product 1

HCID 675002783-{(dimethylamino)methyl}-4-{4-iodo-3-isopropyl-1H-pyrazolo[3,4-b]pyridin-1-yl}benzonitrileYield 40%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

Compound (125a) (0.500 g), 2-picoline-borane complex (0.166 g), and dimethylamine (0.216 mL) were dissolved in acetic acid (1.0 mL) and methanol (10 mL), followed by stirring at room temperature for 12 hr. The reaction solution was concentrated, and the residue was purified by basic silica gel column chromatography (hexane/ethyl acetate) to obtain 3-{(dimethylamino)methyl}-4-{4-iodo-3-isopropyl-1H-pyrazolo[3,4-b]pyridin-1-yl}benzonitrile (0.213 g, 40%). This 3-{(dimethylamino)methyl}-4-{4-iodo-3-isopropyl-1H-pyrazolo[3,4-b]pyridin-1-yl}benzonitrile was dissolved in DMSO (1.6 mL), and a hydrogen peroxide solution (30 wt %) (0.060 mL) and a 4 mol % aqueous sodium hydroxide solution (0.132 mL) were added to the resulting solution, followed by stirring at room temperature for 20 min. Water was added to the reaction solution, and the precipitate was collected by filtration and was dried under reduced pressure to obtain 3-{(dimethylamino)methyl}-4-{4-iodo-3-isopropyl-1H-pyrazolo[3,4-b]pyridin-1-yl}benzamide (0.144 g, 65%). According to Example 97(2), compound (126) (64%) was prepared as a white solid using 3-{(dimethylamino)methyl}-4-{4-iodo-3-isopropyl-1H-pyrazolo[3,4-b]pyridin-1-yl}benzamide instead of compound (97a) and using 4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazole hydrochloride instead of 4-phenyl-1H-imidazole.

Workup

  1. concentrationThe reaction solution was concentrated
  2. customthe residue was purified by basic silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-5746497405534183a71e4a5031b2e789
Source dataset
uspto-grants-2016_03
Patent number
US09273045B2

Reaction notes

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