Diglyme → 2-(2,2-Diethoxyethyl)-4,6-bis(4-fluorophenyl)-5-(4-pyridyl)pyrazolo[3,4-b]pyridine

HRID 42587Notes

Reaction equation

HRID 42587 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)=[C:12]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[N:11]=[C:10]3[NH:27][N:28]=[CH:29][C:9]=23)=[CH:4][CH:3]=1.[OH-].[K+].Br[CH2:33][CH:34]([O:38][CH2:39][CH3:40])[O:35][CH2:36][CH3:37].COCCOCCOC>O.CCOC(C)=O>[CH2:36]([O:35][CH:34]([O:38][CH2:39][CH3:40])[CH2:33][N:28]1[CH:29]=[C:9]2[C:10]([N:11]=[C:12]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[C:13]([C:14]3[CH:15]=[CH:16][N:17]=[CH:18][CH:19]=3)=[C:8]2[C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)=[N:27]1)[CH3:37].[CH2:36]([O:35][CH:34]([O:38][CH2:39][CH3:40])[CH2:33][N:27]1[C:10]2=[N:11][C:12]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)=[C:13]([C:14]3[CH:15]=[CH:16][N:17]=[CH:18][CH:19]=3)[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)=[C:9]2[CH:29]=[N:28]1)[CH3:37]

Participants

7

Reactant 4

HCID 8150DiglymeHCID 14797Potassium HydroxideHCID 74852Ethane, 2-bromo-1,1-diethoxy-HCID 119613744,6-Bis(4-fluorophenyl)-5-(4-pyridyl)-1H-pyrazolo[3,4-b]pyridine

Product 2

HCID 684434952-(2,2-Diethoxyethyl)-4,6-bis(4-fluorophenyl)-5-(4-pyridyl)pyrazolo[3,4-b]pyridineYield 53%HCID 68445205HCID 68445205, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 22728543Water ethylacetateSolvent

Conditions

Temperature
100 °C

Procedure

In a volumetric flask 4,6-bis(4-fluorophenyl)-5-(4-pyridyl)-1H-pyrazolo[3,4-b]pyridine (0.20 g, 0.5 mmol, obtained in example 1), KOH (0.03 g, 0.5 mmol), 2-bromo-1,1-diethoxyethane (0.10 g, 0.5 mmol) and 1-methoxy-2-(2-methoxyethoxy)ethane (2 mL) were introduced under argon atmosphere. The mixture was heated to 100° C. and stirred at this temperature overnight. It was allowed to cool and a mixture of H2O-EtOAc was added. The phases were separated and the aqueous phase was extracted with EtOAc. The combined organic phases were dried over Na2SO4 and concentrated to dryness. The crude product obtained was purified by chromatography on silica gel using hexane-EtOAc mixtures of increasing polarity as eluent, to afford 139 mg of 2-(2,2-diethoxyethyl)-4,6-bis(4-fluorophenyl)-5-(4-pyridyl)pyrazolo[3,4-b]pyridine (yield: 53%) and 60 mg of 1-(2,2-diethoxyethyl)-4,6-bis(4-fluorophenyl)-5-(4-pyridyl)pyrazolo[3,4-b]pyridine (yield: 24%).

Workup

  1. temperatureto cool
  2. additionwas added
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with EtOAc
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. concentrationconcentrated to dryness
  7. customThe crude product obtained
  8. customwas purified by chromatography on silica gel
  9. temperatureof increasing polarity as eluent

Sources & evidence

ORD record
ord-6e4b4d4581334e88b299705a8deef39f
Source dataset
uspto-grants-2013_09
Patent number
US08536194B2

Reaction notes

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