Cyanoacetic acid → 3-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]-3-oxopropanenitrile

HRID 409109Notes

Reaction equation

HRID 409109 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:5]=[CH:4][C:3]=1[C:15]1[C:23]2[C:18](=[N:19][CH:20]=[N:21][C:22]=2[NH2:24])[N:17]([C@@H:25]2[CH2:30][CH2:29][CH2:28][NH:27][CH2:26]2)[N:16]=1.[C:31]([CH2:33][C:34](O)=[O:35])#[N:32].N1(C(N2C=CN=C2)=O)C=CN=C1>ClCCl>[NH2:24][C:22]1[N:21]=[CH:20][N:19]=[C:18]2[N:17]([C@@H:25]3[CH2:30][CH2:29][CH2:28][N:27]([C:34](=[O:35])[CH2:33][C:31]#[N:32])[CH2:26]3)[N:16]=[C:15]([C:3]3[CH:4]=[CH:5][C:6]([O:8][C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=4)=[CH:7][C:2]=3[F:1])[C:23]=12

Participants

5

Reactant 3

HCID 9740Cyanoacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 710152843-(2-fluoro-4-phenoxyphenyl)-1-(3R)-3-piperidinyl-1H-Pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 867144983-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]-3-oxopropanenitrileYield 45.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Into a 100 mL round-bottom flask, was placed a solution of 3-(2-fluoro-4-phenoxyphenyl)-1-[(3R)-piperidin-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (190 mg, 0.47 mmol, 1.00 equiv) in dichloromethane (50 mL), 2-cyanoacetic acid (60 mg, 0.71 mmol, 1.50 equiv), and 1-[(1H-imidazol-1-yl)carbonyl]-1H-imidazole (114 mg, 0.70 mmol, 1.50 equiv). The resulting solution was stirred for 24 h at room temperature and then diluted with dichloromethane. The resulting mixture was washed with NH4Cl and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was loaded onto a silica gel column and eluted with dichloromethane/methanol (100:1) to give 100 mg (45%) of 3-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]-3-oxopropanenitrile as a white solid.

Workup

  1. customInto a 100 mL round-bottom flask, was placed
  2. washThe resulting mixture was washed with NH4Cl
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under vacuum
  5. washeluted with dichloromethane/methanol (100:1)

Sources & evidence

ORD record
ord-2d5fab83c57140d296ba3b50ae1b05fd
Source dataset
uspto-grants-2014_06
Patent number
US08759358B1

Reaction notes

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