Cyanoacetic acid → HCID 86714511, compound

HRID 1187609Notes

Reaction equation

HRID 1187609 reaction equation
[F:1][C:2]1([F:32])[CH2:6][NH:5][C@H:4]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[N:15][C:16]([NH2:17])=[C:11]3[C:10]([C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[CH:20][C:19]=3[F:31])=[N:9]2)[CH2:3]1.[C:33]([CH2:35][C:36](O)=[O:37])#[N:34].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl>[NH2:17][C:16]1[N:15]=[CH:14][N:13]=[C:12]2[N:8]([CH2:7][C@@H:4]3[CH2:3][C:2]([F:1])([F:32])[CH2:6][N:5]3[C:36](=[O:37])[CH2:35][C:33]#[N:34])[N:9]=[C:10]([C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[CH:20][C:19]=3[F:31])[C:11]=12

Participants

5

Reactant 3

HCID 9740Cyanoacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86714509HCID 86714509, compound

Product 1

HCID 86714511HCID 86714511, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1-[[(2S)-4,4-difluoropyrrolidin-2-yl]methyl]-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (850 mg, crude), 2-cyanoacetic acid (120 mg, 1.31 mmol, 1.29 equiv) and TEA (650 mg, 6.45 mmol, 5.00 equiv) in dichloromethane (30 mL), was added HATU (500 mg, 1.32 mmol, 1.29 equiv). The resulting solution was stirred at room temperature overnight. The mixture was diluted with DCM, washed with HCl (2N), sat. NaHCO3, brine, dried over sodium sulfate and concentrated. The residue was submitted to chromatography (SiO2, DCM: MeOH=30:1) to give 0.4 g (77%) of 3-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-4,4-difluoropyrrolidin-1-yl]-3-oxopropanenitrile as a pale yellow solid.

Workup

  1. washwashed with HCl (2N), sat. NaHCO3, brine
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-6897ca994a9046778b8afcc1e95375de
Source dataset
uspto-grants-2014_03
Patent number
US08673925B1

Reaction notes

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