Cyanoacetic acid → N-[(1R)-2-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]-1-methyl-ethyl]-2-cyano-acetamide

HRID 409178Notes

Reaction equation

HRID 409178 reaction equation
[NH2:1][C@H:2]([CH3:28])[CH2:3][N:4]1[C:8]2=[N:9][CH:10]=[N:11][C:12]([NH2:13])=[C:7]2[C:6]([C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:16][C:15]=2[F:27])=[N:5]1.[C:29]([CH2:31][C:32](O)=[O:33])#[N:30].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[NH2:13][C:12]1[N:11]=[CH:10][N:9]=[C:8]2[N:4]([CH2:3][C@H:2]([NH:1][C:32](=[O:33])[CH2:31][C:29]#[N:30])[CH3:28])[N:5]=[C:6]([C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)=[CH:16][C:15]=3[F:27])[C:7]=12

Participants

5

Reactant 3

HCID 9740Cyanoacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 710152621-[(2R)-2-aminopropyl]-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 86714555N-[(1R)-2-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]-1-methyl-ethyl]-2-cyano-acetamideYield 98%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-[(2R)-2-aminopropyl]-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-amine (1826.mg, 4.83 mmol), 2-cyanoacetic acid (821 mg, 9.7 mmol) and TEA (2.0 mL, 14.5 mmol) in DMF (25 mL) was added HATU (2.75 g, 7.24 mmol). The reaction mixture was stirred at room temperature for 20 hr. The mixture was then evaporated to an oil and dissolved in ethyl acetate (100 mL) and washed with 5% citric acid (50 mL) and brine. The organic layer was dried (MgSO4), filtered and evaporated. The crude material was purified by Isolera (10 g col, 2%-6% MeOH/DCM) to obtain 2.1 g (98%) of N-[(1R)-2-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]-1-methyl-ethyl]-2-cyano-acetamide.

Workup

  1. customThe mixture was then evaporated to an oil
  2. dissolutiondissolved in ethyl acetate (100 mL)
  3. washwashed with 5% citric acid (50 mL) and brine
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude material was purified by Isolera (10 g col, 2%-6% MeOH/DCM)

Sources & evidence

ORD record
ord-6e7952d578fb45a4baafb9b1697de540
Source dataset
uspto-grants-2014_06
Patent number
US08759358B1

Reaction notes

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