Piperidine → (R)-2-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-3-cyclopropylacrylonitrile

HRID 1850937Notes

Reaction equation

HRID 1850937 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:24]3[CH2:29][CH2:28][CH2:27][N:26]([C:30](=[O:34])[CH2:31][C:32]#[N:33])[CH2:25]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.N1[CH2:40][CH2:39][CH2:38][CH2:37]C1.C1(C=O)CC1>CO>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:24]3[CH2:29][CH2:28][CH2:27][N:26]([C:30]([C:31](=[CH:37][CH:38]4[CH2:40][CH2:39]4)[C:32]#[N:33])=[O:34])[CH2:25]3)[N:9]=[C:10]([C:11]3[CH:12]=[CH:13][C:14]([O:17][C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[CH:15][CH:16]=3)[C:3]=12

Participants

5

Reactant 3

HCID 8082PiperidineHCID 123114CyclopropanecarboxaldehydeHCID 710156883-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)-3-oxopropanenitrile

Product 1

HCID 71015693(R)-2-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-3-cyclopropylacrylonitrileYield 65%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 3-[3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]-3-oxopropanenitrile (120 mg, 0.26 mmol, 1.00 equiv), piperidine (27 mg, 0.28 mmol, 1.07 equiv) and cyclopropanecarbaldehyde (28 mg, 0.40 mmol, 1.51 equiv) in methanol (8 mL) was stirred in sealed tube at room temperature for 24 h. The resulting mixture was concentrated under vacuum and the residue was purified on a silica gel column eluted with dichloromethane/methanol (100/1) to give 85.4 mg (64%) of the title compound as a white solid. MS (ESI, pos. ion) m/z: 506 (M+1). 1HNMR (300 MHz, CDCl3, ppm) 8.392 (1H, s), 7.676˜7.581 (2H, t), 7.445˜7.393 (2H, t), 7.202˜7.097 (5H, m), 6.601˜6.566 (1H, d, J=10.5), 5.737 (2H, s), 5.010˜4.912 (1H, m), 4.691˜3.185 (4H, m), 2.464˜2.035 (5H, m), 1.275˜0.876 (4H, m).

Workup

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. customthe residue was purified on a silica gel column
  3. washeluted with dichloromethane/methanol (100/1)

Sources & evidence

ORD record
ord-cba98b49add548bc9e86a078cf88235e
Source dataset
uspto-grants-2015_02
Patent number
US08957080B2

Reaction notes

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