Piperidine → (R)-2-(2-((4-amino-3-(4-(3,5-difluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)pyrrolidine-1-carbonyl)-3-cyclopropylacrylonitrile

HRID 409079Notes

Reaction equation

HRID 409079 reaction equation
[CH:1]1([CH:4]=O)[CH2:3][CH2:2]1.N1CCCCC1.[NH2:12][C:13]1[N:18]=[CH:17][N:16]=[C:15]2[N:19]([CH2:37][C@H:38]3[CH2:42][CH2:41][CH2:40][N:39]3[C:43](=[O:47])[CH2:44][C:45]#[N:46])[N:20]=[C:21]([C:22]3[CH:27]=[CH:26][C:25]([O:28][C:29]4[CH:34]=[C:33]([F:35])[CH:32]=[C:31]([F:36])[CH:30]=4)=[CH:24][CH:23]=3)[C:14]=12>CO>[NH2:12][C:13]1[N:18]=[CH:17][N:16]=[C:15]2[N:19]([CH2:37][C@H:38]3[CH2:42][CH2:41][CH2:40][N:39]3[C:43]([C:44](=[CH:4][CH:1]3[CH2:2][CH2:3]3)[C:45]#[N:46])=[O:47])[N:20]=[C:21]([C:22]3[CH:27]=[CH:26][C:25]([O:28][C:29]4[CH:30]=[C:31]([F:36])[CH:32]=[C:33]([F:35])[CH:34]=4)=[CH:24][CH:23]=3)[C:14]=12

Participants

5

Reactant 3

HCID 8082PiperidineHCID 123114CyclopropanecarboxaldehydeHCID 710157173-[(2R)-2-([4-amino-3-[4-(3,5-difluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)pyrrolidin-1-yl]-3-oxopropanenitrile

Product 1

HCID 86714479(R)-2-(2-((4-amino-3-(4-(3,5-difluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)pyrrolidine-1-carbonyl)-3-cyclopropylacrylonitrileYield 49%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

Into a 10-mL round-bottom flask, was placed cyclopropanecarbaldehyde (28.7 mg, 0.41 mmol, 2.00 equiv), piperidine (17.4 mg, 0.20 mmol, 1.00 equiv), 3-[(2R)-2-([4-amino-3-[4-(3,5-difluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)pyrrolidin-1-yl]-3-oxopropanenitrile (100 mg, 0.20 mmol, 1.00 equiv), and methanol (5 mL). The resulting solution was stirred for 12 h at 25° C. and then concentrated under vacuum. The residue was loaded onto a silica gel column and eluted with dichloromethane/methanol (50/1) to give 53.12 mg (45%) of the title compound as an off-white solid. LC-MS: (ES, m/z): MS (ESI, pos. ion) m/z: 541 (M+1). 1H-NMR: (CDCl3, ppm): 1HNMR (300 MHz, CD3OD, ppm), 8.283 (1H, s), 7.777˜7.806 (2H, t), 7.269˜7.298 (2H, t), 6.703˜6.754 (3H, t), 6.455˜6.600 (1H, d), 4.400˜4.878 (3H, m), 3.338˜3.618 (2H, m), 1.700˜2.188 (4H, m), 1.280˜1.305 (4H, m), 0.710˜0.912 (2H, m).

Workup

  1. customInto a 10-mL round-bottom flask, was placed
  2. concentrationconcentrated under vacuum
  3. washeluted with dichloromethane/methanol (50/1)

Sources & evidence

ORD record
ord-682aeb39f93c40269a17c7dc94cfe32a
Source dataset
uspto-grants-2014_06
Patent number
US08759358B1

Reaction notes

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