Cyanoacetic acid → HCID 86714511, compound

HRID 1854963Notes

Reaction equation

HRID 1854963 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-78d78c1faa794c358f06d6ab40aeba0b
Source dataset
uspto-grants-2015_02
Patent number
US08962831B2

Reaction notes

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