Cesium carbonate → 3-methyl-4-{4-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)-3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-1-yl}benzonitrile

HRID 921575Notes

Reaction equation

HRID 921575 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([C:15]3[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][C:16]=3[CH3:23])[N:9]=[C:10]([C:11]([F:14])([F:13])[F:12])[C:3]=12.COC1C2C(=C3C(=CC=2)C(OC)=CC=N3)N=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl.[CH3:49][N:50]1[CH:54]=[C:53]([C:55]2[N:56]=[CH:57][NH:58][CH:59]=2)[CH:52]=[N:51]1>CS(C)=O.C(OCC)(=O)C.[Cu-]=O>[CH3:23][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][C:15]=1[N:8]1[C:4]2=[N:5][CH:6]=[CH:7][C:2]([N:58]3[CH:59]=[C:55]([C:53]4[CH:52]=[N:51][N:50]([CH3:49])[CH:54]=4)[N:56]=[CH:57]3)=[C:3]2[C:10]([C:11]([F:14])([F:13])[F:12])=[N:9]1)[C:19]#[N:20]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 104622984,7-Dimethoxy-1,10-phenanthrolineHCID 675025754-{4-Chloro-3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-1-yl}-3-methylbenzonitrileHCID 178478913HCID 178478913, compound

Product 1

HCID 675010733-methyl-4-{4-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)-3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-1-yl}benzonitrileYield 38%

Reagents, catalysts & solvents 3

HCID 178419072HCID 178419072, compoundCatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

Compound (154e) (1.66 g), copper(I) oxide (0.070 g), 4,7-dimethoxy-1,10-phenanthroline (0.214 g), cesium carbonate (5.46 g), polyethylene glycol (Mn=3400) (0.250 g), and 4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazole hydrochloride (1.20 g) were suspended in DMSO (15 mL), followed by stirring at 120° C. for 2 hr. The reaction solution was diluted with ethyl acetate, and insoluble matters were filtered by celite. The filtrate was distributed between ethyl acetate and water, and the organic layer was washed with saturated saline. The organic layer after the washing was dried over anhydrous sodium sulfate, and the solvent was distilled away to obtain 3-methyl-4-{4-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)-3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-1-yl}benzonitrile, which was used in the subsequent reaction without being purified. TFA (5.0 mL) and sulfuric acid (0.5 mL) were added to this 3-methyl-4-{4-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)-3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-1-yl}benzonitrile, followed by stirring at room temperature for 2 days. The reaction solution was cooled in an ice bath and was neutralized with sodium hydroxide. The reaction solution was distributed between ethyl acetate and water, and the organic layer was washed with saturated saline. The organic layer after the washing was dried over anhydrous sodium sulfate, and the solvent was distilled away. Ethanol was added to the residue, and the precipitate was collected by filtration and dried under reduced pressure to obtain compound (154) (0.881 g, the second stage yield: 38%).

Workup

  1. filtrationwere filtered by celite
  2. washthe organic layer was washed with saturated saline
  3. dry with materialThe organic layer after the washing was dried over anhydrous sodium sulfate
  4. distillationthe solvent was distilled away

Sources & evidence

ORD record
ord-669a261f09ba4db686b2eadc67d811bf
Source dataset
uspto-grants-2016_03
Patent number
US09273045B2

Reaction notes

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