Acetic Acid → 2-(4-Isopropylpiperazin-1-yl)isonicotinonitrile

HRID 276780Notes

Reaction equation

HRID 276780 reaction equation
[N:1]1([C:7]2[CH:8]=[C:9]([CH:12]=[CH:13][N:14]=2)[C:10]#[N:11])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C(O)(=O)C.[CH3:19][C:20]([CH3:22])=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCl>[CH:20]([N:4]1[CH2:3][CH2:2][N:1]([C:7]2[CH:8]=[C:9]([CH:12]=[CH:13][N:14]=2)[C:10]#[N:11])[CH2:6][CH2:5]1)([CH3:22])[CH3:19]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 180AcetoneHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 162279862-(Piperazin-1-yl)pyridine-4-carbonitrile

Product 1

HCID 186715252-(4-Isopropylpiperazin-1-yl)isonicotinonitrileYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-piperazin-1-yl-isonicotinonitrile (10 g, 53 mmol), glacial acetic acid (4.26 ml, 4.5 g, 74.4 mmol, 1.4 equiv) and acetone (4.29 ml, 3.39 g, 58 mmol, 1.1 equiv) in anhydrous dichloromethane was added sodium triacetoxyborohydride (13.5 g, 63.8 mmol, 1.2 equiv). The reaction was stirred overnight, then an aqueous solution of 1 N NaOH solution was added (150 ml) and the mixture was extracted once with dichloromethane, then twice with a solution of 10% methanol/dichloromethane. The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Purification of the residue by flash column chromatography (5% methanol/CH2Cl2 grading to 10% methanol/CH2Cl2) provided the desired product (6.52 g, 59%).

Workup

  1. extractionthe mixture was extracted once with dichloromethane
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification of the residue by flash column chromatography (5% methanol/CH2Cl2 grading to 10% methanol/CH2Cl2)

Sources & evidence

ORD record
ord-e14bb971f8be4335955395148d3cd03f
Source dataset
uspto-grants-2002_03
Patent number
US06355635B1

Reaction notes

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