Cyclopropylamine → Nevirapine

HRID 866021

反応式

HRID 866021 の反応式
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.[O-2].[Ca+2].[CH:21]1([NH2:24])[CH2:23][CH2:22]1>>[CH:21]1([N:24]2[C:2]3[N:3]=[CH:4][CH:5]=[CH:6][C:7]=3[C:8](=[O:9])[NH:10][C:11]3[C:16]([CH3:17])=[CH:15][CH:14]=[N:13][C:12]2=3)[CH2:23][CH2:22]1

参加物

4

反応物 3

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

生成物 1

HCID 4463Nevirapine収率 83.5%

反応条件

温度
130 °C

実験手順

117.5 kg of 2-chloro-N-(2-chloro-4-methyl-3-pyridyl)-3-pyridine carboxamide (4), 23.3 kg of calcium oxide and 59.4 kg of cyclopropylamine (molar ratio: 1:1:2.5) are heated to between 135° and 145° C. in 235 l ofdiglyme (diethylene glycoldimethylether) in a 500 l VA autoclave over a period of 6 to 8 hours. The reaction mixture is then cooled to a temperature of 20° to 30° C. and filtered. The filter cake is washed with 58.8 l of diglyme. The filtrates are combined and initially 200 l of solvent is distilled off. The residue is then diluted with a further 117.5 l of diglyme. The resultant diluted solution is added over a period of 20 to 40 minutes to a suspension of 45.0 kg of 60% sodium hydride in 352.5 l of diglyme, heated to 130° C. The storage vessel and conduits are rinsed with a further 55.8 l of diglyme, and the mixture is stirred at a temperature of between 130° and 140° C. for a further 30 to 60 minutes. The majority of the diglyme is then distilled off. Finally, the remaining residue is carefully mixed with 470 l of water. After cooling to a temperature of about 25° C., 235.0 l of cyclohexane and 57.11 of glacial acetic acid are added to the reaction mixture. The mixture is then stirred for about 1 hour at temperature of 10° to 25° C. The resultant suspension is centrifuged and the centrifuged material is then washed with 235.0 l of methyl-tert.-butylether and subsequently with 353.5 l of water and finally with 235 l of ethanol. In this way, after drying, 92.5 kg (83.5% of theory) of 11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one (nevirapine) is isolated.

後処理

  1. temperatureThe reaction mixture is then cooled to a temperature of 20° to 30° C.
  2. filtrationfiltered
  3. washThe filter cake is washed with 58.8 l of diglyme
  4. distillationinitially 200 l of solvent is distilled off
  5. additionThe residue is then diluted with a further 117.5 l of diglyme
  6. additionThe resultant diluted solution is added over a period of 20 to 40 minutes to a suspension of 45.0 kg of 60% sodium hydride in 352.5 l of diglyme
  7. washThe storage vessel and conduits are rinsed with a further 55.8 l of diglyme
  8. distillationThe majority of the diglyme is then distilled off
  9. additionFinally, the remaining residue is carefully mixed with 470 l of water
  10. temperatureAfter cooling to a temperature of about 25° C., 235.0 l of cyclohexane and 57.11 of glacial acetic acid
  11. additionare added to the reaction mixture
  12. stirringThe mixture is then stirred for about 1 hour at temperature of 10° to 25° C
  13. washthe centrifuged material is then washed with 235.0 l of methyl-tert.-butylether and subsequently with 353.5 l of water and finally with 235 l of ethanol
  14. customIn this way, after drying

出典と根拠

ORDレコード
ord-76bfe9bb64c24a369d36aac7f6f249b6
出典データセット
uspto-grants-1996_10
特許番号
US05569760

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