Pyridine → 3-(4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)piperidin-1-yl)-3-oxopropanenitrile

HRID 1854374Notes

Reaction equation

HRID 1854374 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[N:11]3[C:12]4[CH:18]=[CH:17][NH:16][C:13]=4[N:14]=[CH:15][C:10]3=[N:9][N:8]=2)[CH2:3][CH2:2]1.N1C=CC=CC=1.[C:25]([CH2:27][C:28](OC1C(F)=C(F)C(F)=C(F)C=1F)=[O:29])#[N:26]>CN(C=O)C>[C:7]1([CH:4]2[CH2:3][CH2:2][N:1]([C:28](=[O:29])[CH2:27][C:25]#[N:26])[CH2:6][CH2:5]2)[N:11]2[C:12]3[CH:18]=[CH:17][NH:16][C:13]=3[N:14]=[CH:15][C:10]2=[N:9][N:8]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 20402415Perfluorophenyl 2-cyanoacetateHCID 1361988561-(piperidin-4-yl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine

Product 1

HCID 1361988233-(4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)piperidin-1-yl)-3-oxopropanenitrileYield 4.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 1-(piperidin-4-yl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (0.090 g, 0.37 mmol, Example #2) and pyridine (0.12 mL, 1.5 mmol) in DMF (5 mL) was added perfluorophenyl 2-cyanoacetate (0.14 g, 0.56 mmol, Preparation #6). After about 3 h at ambient temperature, the reaction mixture was quenched with MeOH (0.5 mL) and then purified by RP-HPLC (Table 2, Method b). The appropriate fractions were concentrated and lyophilized to afford 3-(4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)piperidin-1-yl)-3-oxopropanenitrile as a white solid (0.005 g, 4%): LC/MS (Table 2, Method a) Rt=1.24 min; MS m/z: 310 (M+H)+.

Workup

  1. customthe reaction mixture was quenched with MeOH (0.5 mL)
  2. custompurified by RP-HPLC (Table 2, Method b)
  3. concentrationThe appropriate fractions were concentrated

Sources & evidence

ORD record
ord-b9e06c2824f3415d8a4f08224f060c64
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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