Piperidine → HCID 86714491, compound

HRID 409095Notes

Reaction equation

HRID 409095 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:26]3[CH2:31][CH2:30][CH2:29][N:28]([C:32](=[O:36])[CH2:33][C:34]#[N:35])[CH2:27]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:19]=4[F:25])=[CH:13][CH:12]=3)[C:3]=12.N1[CH2:42][CH2:41][CH2:40][CH2:39]C1.C1(C=O)CC1>CO>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:26]3[CH2:31][CH2:30][CH2:29][N:28]([C:32]([C:33](=[CH:39][CH:40]4[CH2:42][CH2:41]4)[C:34]#[N:35])=[O:36])[CH2:27]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:19]=4[F:25])=[CH:13][CH:12]=3)[C:3]=12

Participants

5

Reactant 3

HCID 8082PiperidineHCID 123114CyclopropanecarboxaldehydeHCID 867144923-[(3R)-3-[4-amino-3-[4-(2,6-difluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]-3-oxopropanenitrile

Product 1

HCID 86714491HCID 86714491, compoundYield 21.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

Into a 10 mL sealed tube, was placed a solution of 3-[(3R)-3-[4-amino-3-[4-(2,6-difluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]-3-oxopropanenitrile (150 mg, 0.31 mmol, 1.00 equiv) in methanol (5 mL), piperidine (78 mg, 0.92 mmol, 3.0 equiv), and cyclopropanecarbaldehyde (64 mg, 0.91 mmol, 3.0 equiv). The resulting solution was stirred for 12 h at 25° C. and then concentrated under vacuum. The residue was diluted with 10 mL of dichloromethane, and the solution was washed with saturated aqueous ammonium chloride, water and brine. The organics were dried over anhydrous sodium sulfate and concentrated. The residue was loaded onto a silica gel column and eluted with dichloromethane/methanol (20/1) to give 36 mg (21%) of 2-[[(3R)-3-[4-amino-3-[4-(2,6-difluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]carbonyl]-3-cyclopropylprop-2-enenitrile as a white solid.

Workup

  1. customInto a 10 mL sealed tube
  2. concentrationconcentrated under vacuum
  3. additionThe residue was diluted with 10 mL of dichloromethane
  4. washthe solution was washed with saturated aqueous ammonium chloride, water and brine
  5. dry with materialThe organics were dried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. washeluted with dichloromethane/methanol (20/1)

Sources & evidence

ORD record
ord-64a95f722b1d4a2c9ece289f17576755
Source dataset
uspto-grants-2014_06
Patent number
US08759358B1

Reaction notes

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