Cesium carbonate → 4-[3-[(E)-2-(4-chloro-phenyl)-vinyl]-6-(4-hydroxy-phenyl)-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 82025

Reaction equation

HRID 82025 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[C:17]3[C:25](/[CH:26]=[CH:27]/[C:28]4[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=4)=[N:24][N:23]([CH:35]4[CH2:40][CH2:39][CH2:38][CH2:37][O:36]4)[C:18]=3[N:19]=[C:20](Cl)[CH:21]=2)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH:41][C:42]1[CH:47]=[CH:46][C:45](B(O)O)=[CH:44][CH:43]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[C:17]3[C:25](/[CH:26]=[CH:27]/[C:28]4[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=4)=[N:24][N:23]([CH:35]4[CH2:40][CH2:39][CH2:38][CH2:37][O:36]4)[C:18]=3[N:19]=[C:20]([C:45]3[CH:46]=[CH:47][C:42]([OH:41])=[CH:43][CH:44]=3)[CH:21]=2)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27343604-Hydroxyphenylboronic acidHCID 866781604-[6-chloro-3-[(E)-2-(4-chloro-phenyl)-vinyl]-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 1363594974-[3-[(E)-2-(4-chloro-phenyl)-vinyl]-6-(4-hydroxy-phenyl)-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid tert-butyl esterYield 80%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 4-[6-chloro-3-[(E)-2-(4-chloro-phenyl)-vinyl]-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester (1.5 g, 2.56 mmol) in dioxane (38 ml) were added 4-hydroxyphenylboronic acid (0.39 g, 2.81 mmol) and an aqueous solution of cesium carbonate (0.3M, 4.6 mmol). The resulting solution was degassed using argon, tetrakis(triphenylphosphine)palladium (0.14 g, 0.13 mmol) was then added and the reaction mixture was refluxed for 3 hours. Solvents were removed under vacuum. The resulting crude mixture was submitted to a silica gel column chromatography using a gradient of ethyl acetate (0-45%) in cyclohexane to give the title compound (1.32 g, 80%) as a white solid.

Workup

  1. customThe resulting solution was degassed
  2. additionwas then added
  3. temperaturethe reaction mixture was refluxed for 3 hours
  4. customSolvents were removed under vacuum

Sources & evidence

ORD record
ord-4fcdff0bc5b04d0f882d9bbe0214a5df
Source dataset
uspto-grants-2014_09
Patent number
US08846712B2

Linked notes

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