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

HRID 409088Notes

Reaction equation

HRID 409088 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:25]3[CH2:30][CH2:29][CH2:28][N:27]([C:31](=[O:35])[CH2:32][C:33]#[N:34])[CH2:26]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]=[C:20]([F:24])[CH:19]=4)=[CH:13][CH:12]=3)[C:3]=12.[CH:36]1([CH:39]=O)[CH2:38][CH2:37]1.N1CCCCC1.ClCCl>CO>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:25]3[CH2:30][CH2:29][CH2:28][N:27]([C:31]([C:32](=[CH:39][CH:36]4[CH2:38][CH2:37]4)[C:33]#[N:34])=[O:35])[CH2:26]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]=[C:20]([F:24])[CH:19]=4)=[CH:13][CH:12]=3)[C:3]=12

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8082PiperidineHCID 123114CyclopropanecarboxaldehydeHCID 867144853-[(3R)-3-[4-amino-3-[4-(3-fluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]-3-oxopropanenitrile

Product 1

HCID 86714486(R)-2-(3-(4-amino-3-(4-(3-fluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-3-cyclopropylacrylonitrileYield 27.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Into a 50 mL round-bottom flask, was placed a solution of 3-[(3R)-3-[4-amino-3-[4-(3-fluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]-3-oxopropanenitrile (120 mg, 0.25 mmol, 1.00 equiv) in methanol (20 mL), cyclopropanecarbaldehyde (54 mg, 0.77 mmol, 3.00 equiv), piperidine (11 mg, 0.13 mmol, 0.50 equiv), and dichloromethane (5 mL). The resulting solution was stirred for 12 h at room temperature and then concentrated under vacuum. The residue was loaded onto a silica gel column and eluted with dichloromethane/methanol (100:1) to give 36 mg (27%) of the title compounds as a white solid. LC-MS: (ES, m/z): 524 [M+H]+. 1H-NMR: (300 MHz, CDCl3, ppm) 8.396 (1H, s), 7.721˜7.674 (2H, m), 7.393˜7.316 (1H, m), 7.237˜7.191 (2H, m), 6.923˜6.786 (3H, m), 6.607˜6.570 (1H, d, J=11.1), 5.795 (2H, s), 5.018˜4.919 (1H, m), 4.8-3.1 (4H, m), 2.465˜2.269 (5H, m), 1.274 (2H, m), 0.887 (2H, m).

Workup

  1. customInto a 50 mL round-bottom flask, was placed
  2. concentrationconcentrated under vacuum
  3. washeluted with dichloromethane/methanol (100:1)

Sources & evidence

ORD record
ord-943aa23035a04b30bf942cf5d7ed3fc0
Source dataset
uspto-grants-2014_06
Patent number
US08759358B1

Reaction notes

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