Cyclopropylamine → Nevirapine

HRID 866025Notes

Reaction equation

HRID 866025 reaction equation
Cl[C:2]1[C:7]([C:8]([NH:10][C:11]2[C:12](Cl)=[N:13][CH:14]=[CH:15][C:16]=2[CH3:17])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH:19]1([NH2:22])[CH2:21][CH2:20]1.[O-2].[Ca+2]>COCCOCCOC>[CH3:17][C:16]1[CH:15]=[CH:14][N:13]=[C:12]2[N:22]([CH:19]3[CH2:21][CH2:20]3)[C:2]3[N:3]=[CH:4][CH:5]=[CH:6][C:7]=3[C:8](=[O:9])[NH:10][C:11]=12

Participants

5

Reactant 3

HCID 69828CyclopropylamineHCID 6850728CalciumoxideHCID 104238682-Chloro-N-(2-chloro-4-methyl-3-pyridinyl)-3-pyridinecarboxamide

Product 1

HCID 4463Nevirapine

Reagents, catalysts & solvents 1

HCID 8150DiglymeSolvent

Conditions

Temperature
25 °C

Procedure

The process according to claim 4, wherein 2-chloro-N-(2-chloro-4-methyl-3-pyridyl)-3-pyridine carboxamide is heated with cyclopropylamine in the presence of 1 to 2 mol of calcium oxide in diglyme to 135° to 145° C. for 6 to 7 hours, the reaction mixture is then cooled down to 20° to 30° C. and filtered, the filter cake is washed with diglyme and the combined filtrates are concentrated, the residue is then diluted with diglyme and this solution is added to a solution or suspension of sodium hydride in diglyme, heated to 130° to 140° C., and the reaction mixture is kept at a temperature of 130° to 140° C. for 30 minutes to one hour and then the reaction medium is distilled off, the residue is hydrolysed at a temperature of 50° to 80° C. and then cooled to a temperature of about 25° C. and mixed with an inert solvent and an organic acid and the reaction mixture is stirred for about 1 hour at 10° to 25° C., the resultant suspension of the product is separated, washed with an inert solvent, followed by water and alcohol to give nevirapine.

Workup

  1. temperaturethe reaction mixture is then cooled down to 20° to 30° C.
  2. filtrationfiltered
  3. washthe filter cake is washed with diglyme
  4. concentrationthe combined filtrates are concentrated
  5. additionthe residue is then diluted with diglyme
  6. additionthis solution is added to a solution or suspension of sodium hydride in diglyme
  7. temperatureheated to 130° to 140° C.
  8. waitthe reaction mixture is kept at a temperature of 130° to 140° C. for 30 minutes to one hour
  9. distillationthe reaction medium is distilled off
  10. customis hydrolysed at a temperature of 50° to 80° C.
  11. additionmixed with an inert solvent
  12. additionthe resultant suspension of the product
  13. customis separated
  14. washwashed with an inert solvent

Sources & evidence

ORD record
ord-a0160ba1d28945579d4308067eb4e57b
Source dataset
uspto-grants-1996_10
Patent number
US05569760

Reaction notes

Loading…