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

HRID 1850982Notes

Reaction equation

HRID 1850982 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:28]=[CH:29][CH:30]=1)[O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[N:18][C:19]=3[NH2:21])[N:14]([C@@H:22]3[CH2:27][CH2:26][CH2:25][NH:24][CH2:23]3)[N:13]=2)=[CH:8][CH:7]=1.[C:31]([CH2:33][C:34](O)=[O:35])#[N:32].N1(C(N2C=CN=C2)=O)C=CN=C1>ClCCl>[NH2:21][C:19]1[N:18]=[CH:17][N:16]=[C:15]2[N:14]([C@@H:22]3[CH2:27][CH2:26][CH2:25][N:24]([C:34](=[O:35])[CH2:33][C:31]#[N:32])[CH2:23]3)[N:13]=[C:12]([C:9]3[CH:10]=[CH:11][C:6]([O:5][C:4]4[CH:28]=[CH:29][CH:30]=[C:2]([F:1])[CH:3]=4)=[CH:7][CH:8]=3)[C:20]=12

Participants

5

Reactant 3

HCID 9740Cyanoacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 710152963-[4-(3-fluorophenoxy)-phenyl]-1-[(3R)-piperidin-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 867144853-[(3R)-3-[4-amino-3-[4-(3-fluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]-3-oxopropanenitrileYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Into a 100 mL round-bottom flask, was placed a solution of 3-[4-(3-fluorophenoxy)-phenyl]-1-[(3R)-piperidin-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (180 mg, 0.45 mmol, 1.00 equiv) in dichloromethane (50 mL), 2-cyanoacetic acid (56 mg, 0.66 mmol, 1.50 equiv), and 1-[(1H-imidazol-1-yl)carbonyl]-1H-imidazole (108 mg, 0.67 mmol, 1.50 equiv). The resulting solution was stirred for 24 h at room temperature and then diluted with 100 mL dichloromethane. The resulting mixture was washed NH4Cl, 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 120 mg (57%) of 3-[(3R)-3-[4-amino-3-[4-(3-fluorophenoxy)phenyl]-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 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-b9d192a1bb1a4b45a7b8fab849ab0b4f
Source dataset
uspto-grants-2015_02
Patent number
US08957080B2

Reaction notes

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