1-Hydroxybenzotriazole → 6-[4-(6-Bromopyridine-3-carbonyl)piperazin-1-yl]-5-methylnicotinonitrile

HRID 2411296Notes

Reaction equation

HRID 2411296 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=1.[CH3:11][C:12]1[C:13]([N:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)=[N:14][CH:15]=[C:16]([CH3:18])[CH:17]=1.O[N:26]1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(=O)([O-])O.[Na+]>CN(C)C=O.C(N(CC)CC)C>[Br:1][C:2]1[N:3]=[CH:4][C:5]([C:6]([N:22]2[CH2:21][CH2:20][N:19]([C:13]3[C:12]([CH3:11])=[CH:17][C:16]([C:18]#[N:26])=[CH:15][N:14]=3)[CH2:24][CH2:23]2)=[O:8])=[CH:9][CH:10]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 2389326-Bromonicotinic acidHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 584844961-(3,5-Dimethylpyridin-2-yl)piperazine

Product 1

HCID 584845186-[4-(6-Bromopyridine-3-carbonyl)piperazin-1-yl]-5-methylnicotinonitrileYield 74.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

6-Bromonicotinic acid (500 mg), 1-(3,5-dimethylpyridin-2-yl)piperazine (501 mg) described in Preparation Example 79, 1-hydroxybenzotriazole 1 hydrate (379 mg) and triethylamine (0.69 mL) were dissolved in N,N-dimethylformamide (10 mL), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (569 mg) was added, and the mixture was stirred at room temperature overnight. To the reaction mixture was added 5% aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and the solvent was evaporated. The obtained residue was purified by column chromatography (hexane:ethyl acetate) to give the title compound (709 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water and saturated brine
  3. customthe solvent was evaporated
  4. customThe obtained residue was purified by column chromatography (hexane:ethyl acetate)

Sources & evidence

ORD record
ord-a82f9d5fb09d402194ddf8e621edc892
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

Loading…