Water → Nevirapine

HRID 1899389Notes

Reaction equation

HRID 1899389 reaction equation
Cl[C:2]1[C:7]([NH2:8])=[C:6]([CH3:9])[C:5](Cl)=[CH:4][N:3]=1.Cl[C:12]1[N:20]=[CH:19][CH:18]=[CH:17][C:13]=1[C:14](Cl)=[O:15].O.[N:22]1[CH:27]=[CH:26][CH:25]=CC=1>C1CCCCC1.O1CCOCC1.[OH-].[Na+]>[CH:27]1([N:22]2[C:12]3[N:20]=[CH:19][CH:18]=[CH:17][C:13]=3[C:14](=[O:15])[NH:8][C:7]3[C:6]([CH3:9])=[CH:5][CH:4]=[N:3][C:2]2=3)[CH2:25][CH2:26]1

Participants

8

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 27745412-Chloronicotinoyl chlorideHCID 23373359HCID 23373359, compound

Product 1

HCID 4463Nevirapine

Reagents, catalysts & solvents 3

HCID 8078CyclohexaneSolventHCID 14798Sodium HydroxideSolvent2×HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of 90.0 g (0.508 mole) of 2,5-dichloro-4-methyl-3-aminopyridine in 225ml of cyclohexane, 220ml of pyridine, and 50ml of 1,4-dioxane was added in portions over 15 minutes a solution of 100.7g (0.571 mole) of 2-chloronicotinic acid chloride in 200 ml of 1,4-dioxane. At the end of the addition, the reaction temperature reached 50° C. The mixture was stirred at room temperature for 2 days. The wet filter cake was heated at mild reflux overnight in 1l of water containing 25ml of 1N NaOH solution. (The crude product contained 8%-10% of the di-adduct, which is readily hydrolyzed in dilute sodium hydroxide solution to the required product.) The product was collected by filtration and was washed with cold water. The pure product was dried at 60° C. under vacuum to yield 60g (37.3%) (mp:168° C.-171° C.) of 2,6-dichloro-3-(2'-chloro-3'-nicotinyl) carboxamido-4-methylpyridine.

Workup

  1. additionAt the end of the addition
  2. customreached 50° C
  3. temperatureThe wet filter cake was heated

Sources & evidence

ORD record
ord-a6efe026377049ceb3965a969608f709
Source dataset
uspto-grants-1996_11
Patent number
US05571912

Reaction notes

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