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

HRID 1853613Notes

Reaction equation

HRID 1853613 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-747dcf3da7144b358ebd1cf4b8e25016
Source dataset
uspto-grants-2015_02
Patent number
US08962635B2

Reaction notes

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