Acrylonitrile → HCID 118159872, compound

HRID 628419Notes

Reaction equation

HRID 628419 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[NH:8]1[CH2:11][CH:10]([N:12]2[CH:16]=[CH:15][C:14]([C:17]3[N:29]([CH2:30][C:31]4[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[CH:32]=4)[C:20]4[CH:21]=[CH:22][C:23]5[N:24]([C:25]([CH3:28])=[N:26][N:27]=5)[C:19]=4[CH:18]=3)=[N:13]2)[CH2:9]1.C([O-])([O-])=O.[K+].[K+].[C:44](#[N:47])[CH:45]=[CH2:46].N12CCCN=C1CCCCC2>CC#N.CO>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[Cl:37][C:33]1[CH:32]=[C:31]([CH:36]=[CH:35][CH:34]=1)[CH2:30][N:29]1[C:20]2[CH:21]=[CH:22][C:23]3[N:24]([C:25]([CH3:28])=[N:26][N:27]=3)[C:19]=2[CH:18]=[C:17]1[C:14]1[CH:15]=[CH:16][N:12]([CH:10]2[CH2:9][N:8]([CH2:46][CH2:45][C:44]#[N:47])[CH2:11]2)[N:13]=1

Participants

7

Reactant 4

HCID 7855Acrylonitrile2×HCID 11430Potassium CarbonateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 118159853HCID 118159853, compound

Product 1

HCID 118159872HCID 118159872, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent2×

Procedure

7-(1-Azetidin-3-yl-1H-pyrazol-3-yl)-6-(3-chlorobenzyl)-1-methyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridine trifluoroacetate salt (19 mg, 0.025 mmol, prepared as in Example 156) in MeCN (1.0 mL) was treated with K2CO3 (34 mg, 0.25 mmol) and 2-propenenitrile (3.3 μL, 0.050 mmol, Aldrich). The reaction was stirred at room temperature for 2 hours and then was heated at 40° C. for 2 hours. The reaction mixture was allowed to cool to room temperature and additional 2-propenenitrile (3.3 μL, 0.050 mmol, Aldrich) and 1,8-diazabicyclo[5.4.0]undec-7-ene (3.7 μL, 0.025 mmol, Aldrich) were added. After stirring at room temperature for 3 days, the reaction was diluted with MeOH (2 mL) and MeCN (2 mL) and was purified via preparative HPLC-MS (Waters SunFire C18, eluting with a gradient of MeCN/H2O containing 0.1% TFA).

Workup

  1. temperaturewas heated at 40° C. for 2 hours
  2. temperatureto cool to room temperature
  3. stirringAfter stirring at room temperature for 3 days
  4. customwas purified via preparative HPLC-MS (Waters SunFire C18
  5. washeluting with a gradient of MeCN/H2O containing 0.1% TFA)

Sources & evidence

ORD record
ord-b0a4a7f052864b71b4d3b4978cd44997
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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