Water → N-(2-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-2-cyano-3-cyclopropylacrylamide

HRID 409151Notes

Reaction equation

HRID 409151 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:24][CH2:25][NH:26][C:27](=[O:31])[CH2:28][C:29]#[N:30])[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)[C:3]=12.[CH2:32]1[CH:34]([CH:35](O)C#N)[CH2:33]1.N1CCCCC1.O>CO>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:24][CH2:25][NH:26][C:27](=[O:31])[C:28]([C:29]#[N:30])=[CH:35][CH:34]3[CH2:32][CH2:33]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)[C:3]=12

Participants

6

Reactant 4

HCID 962WaterHCID 8082PiperidineHCID 113893592-Cyclopropyl-2-hydroxyacetonitrileHCID 86714528N-(2-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-2-cyanoacetamide

Product 1

HCID 71015172N-(2-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-2-cyano-3-cyclopropylacrylamideYield 38%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of N-(2-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-2-cyanoacetamide (90 mg, 0.22 mole), cyclopropylcarboxaldehyde (18 mg, 0.26 mmole) and piperidine (22 mg, 0.26 mmole) in MeOH (5 mL) was stirred for 3 hr at room temperature. Then water was added and extracted with ethyl acetate. The organic layers were combined and washed with aq. NaHCO3 and brine, then dried (Na2SO4), filtered and concentrated. The residue was purified by column chromatography (3% MeOH/DCM) to provide 39 mg (38% yield) of the title compound as a white solid. LCMS m/z 466 (M+H)+.

Workup

  1. extractionextracted with ethyl acetate
  2. washwashed with aq. NaHCO3 and brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (3% MeOH/DCM)

Sources & evidence

ORD record
ord-85d1c70077df4387867e4079589b1624
Source dataset
uspto-grants-2014_06
Patent number
US08759358B1

Reaction notes

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