Water → 1-{2-[4-(4-Chloro-3-methoxy-phenyl)-piperazin-1-yl]-2-oxo-ethyl}-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

HRID 1866590Notes

Reaction equation

HRID 1866590 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14](=[O:26])[CH2:15][N:16]3[C:20]4=[N:21][CH:22]=[CH:23][CH:24]=[C:19]4[C:18](I)=[N:17]3)[CH2:10][CH2:9]2)=[CH:4][C:3]=1[O:27][CH3:28].[CH3:29][N:30](C=O)C.O>CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].[C-]#N.[C-]#N.[Zn+2].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]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14](=[O:26])[CH2:15][N:16]3[C:20]4=[N:21][CH:22]=[CH:23][CH:24]=[C:19]4[C:18]([C:29]#[N:30])=[N:17]3)[CH2:10][CH2:9]2)=[CH:4][C:3]=1[O:27][CH3:28]

Participants

8

Reactant 3

HCID 962WaterHCID 6228DimethylformamideHCID 160060311-[4-(4-Chloro-3-methoxy-phenyl)-piperazin-1-yl]-2-(3-iodo-pyrazolo[3,4-b]pyridin-1-yl)-ethanone

Product 1

HCID 160055291-{2-[4-(4-Chloro-3-methoxy-phenyl)-piperazin-1-yl]-2-oxo-ethyl}-1H-pyrazolo[3,4-b]pyridine-3-carbonitrileYield 93%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a 2000 ml flask was charged with 1-[4-(4-Chloro-3-methoxy-phenyl)-piperazin-1-yl]-2-(3-iodo-pyrazolo[3,4-b]pyridin-1-yl)-ethanone (see U.S. application Ser. No. 11/474,132, published as U.S. 20070010524, 40 g, 78.1 mmol), dppf (3.86 g, 6.96 mmol), Zn(CN)2 (9.6 g, 81.6 mmol), DMF (360 ml) and H2O (20 ml). The resulting suspension was degassed using N2 for 5 min, followed by addition of Pd2(dba)3 (4.24 g, 4.64 mmol). The reaction mixture was heated under N2 at 90° C. for 2 h (monitor by TLC and LC-MS). After cooling to room temperature, diluted with EtOAc (1500 ml), filtered to remove the precipitate and washed with H2O (1000×2 ml), saturated EDTA.4Na (800 ml×2), brine and dried over Na2SO4. After evaporation of the solvent, ether (150 mL) was added and stirred for 2 h. The resulting solid was filtered to give the desired product 30 g (93%) as light yellow powder. Recrystallization from refluxing CH3CN (160 mL) afforded 26 g (80%) light yellow crystals: mp 183-185° C.; Rt=2.38 min; MS (ES) M+H expect 411.1, found 41.1.

Workup

  1. customThe resulting suspension was degassed
  2. customfor 5 min
  3. temperatureAfter cooling to room temperature
  4. filtrationfiltered
  5. customto remove the precipitate
  6. washwashed with H2O (1000×2 ml), saturated EDTA
  7. dry with material4Na (800 ml×2), brine and dried over Na2SO4
  8. customAfter evaporation of the solvent, ether (150 mL)
  9. additionwas added
  10. filtrationThe resulting solid was filtered

Sources & evidence

ORD record
ord-eef011d98caf46e59135ac366ad125f4
Source dataset
uspto-grants-2009_12
Patent number
US07629344B2

Reaction notes

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