Potassium Carbonate → 1-[4-(4-Chloro-2-fluoro-5-methoxyphenyl)-2-(S)-methylpiperazin-1-yl]-2-pyrazolo[3,4-b]pyridine-1-ylethanone

HRID 390537Notes

Reaction equation

HRID 390537 reaction equation
Cl[CH2:2][C:3]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[C:15]([O:17][CH3:18])[C:14]([Cl:19])=[CH:13][C:12]=2[F:20])[CH2:7][C@@H:6]1[CH3:21])=[O:4].[NH:22]1[C:26]2=[N:27][CH:28]=[CH:29][CH:30]=[C:25]2[CH:24]=[N:23]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C>[Cl:19][C:14]1[C:15]([O:17][CH3:18])=[CH:16][C:11]([N:8]2[CH2:9][CH2:10][N:5]([C:3](=[O:4])[CH2:2][N:22]3[C:26]4=[N:27][CH:28]=[CH:29][CH:30]=[C:25]4[CH:24]=[N:23]3)[C@@H:6]([CH3:21])[CH2:7]2)=[C:12]([F:20])[CH:13]=1.[Cl:19][C:14]1[C:15]([O:17][CH3:18])=[CH:16][C:11]([N:8]2[CH2:9][CH2:10][N:5]([C:3](=[O:4])[CH2:2][N:23]3[CH:24]=[C:25]4[C:26]([N:27]=[CH:28][CH:29]=[CH:30]4)=[N:22]3)[C@@H:6]([CH3:21])[CH2:7]2)=[C:12]([F:20])[CH:13]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27558501H-pyrazolo(3,4-b)pyridineHCID 576427672-Chloro-1-[(S)-4-(4-chloro-2-fluoro-5-methoxy-phenyl)-2-methyl-piperazin-1-yl]-ethanone

Product 2

HCID 119845661-[4-(4-Chloro-2-fluoro-5-methoxyphenyl)-2-(S)-methylpiperazin-1-yl]-2-pyrazolo[3,4-b]pyridine-1-ylethanoneHCID 160068551-[4-(4-chloro-2-fluoro-5-methoxyphenyl)-2-(S)-methylpiperazin-1-yl]-2-pyrazolo[3,4-b]pyridine-2-ylethanone

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

2-Chloro-1-[4-(4-chloro-2-fluoro-5-methoxyphenyl)-2-(S)-methylpiperazin-1-yl]ethanone (arylpiperazine) (4.81 g, 14.32 mmol, 1 equiv), 1H-pyrazolo[3,4-b]pyridine (2.27 g, 17.18 mmol, 1.2 equiv), and potassium carbonate (20.00 g, 143.2 mmol, 10 equiv) were dissolved in dimethylformamide (DMF) (10 mL) and heated at 80° C. for 1 hour, then cooled to room temperature. The resultant mixture was diluted with ethyl acetate (300 mL), and washed with water (3×150 mL) and brine (100 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo to provide a crude residue. The crude residue was purified by flash chromatography (silica, 100% ethyl acetate with 1% triethylamine to 100% acetone with 1% triethylamine) provided 1-[4-(4-Chloro-2-fluoro-5-methoxyphenyl)-2-(S)-methylpiperazin-1-yl]-2-pyrazolo[3,4-b]pyridine-1-ylethanone (2.3 g) and 1-[4-(4-chloro-2-fluoro-5-methoxyphenyl)-2-(S)-methylpiperazin-1-yl]-2-pyrazolo[3,4-b]pyridine-2-ylethanone (2.5 g).

Workup

  1. temperaturecooled to room temperature
  2. washwashed with water (3×150 mL) and brine (100 mL)
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customto provide a crude residue
  6. customThe crude residue was purified by flash chromatography (silica, 100% ethyl acetate with 1% triethylamine to 100% acetone with 1% triethylamine)

Sources & evidence

ORD record
ord-63f9844945154a3086e8d8865f12dd28
Source dataset
uspto-grants-2013_02
Patent number
US08383630B2

Reaction notes

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