Cyclopropylamine → Nevirapine

HRID 866023

反応式

HRID 866023 の反応式
[CH:1]1([NH2:4])[CH2:3][CH2:2]1.Cl[C:6]1[C:11]([C:12]([NH:14][C:15]2[C:16](Cl)=[N:17][CH:18]=[CH:19][C:20]=2[CH3:21])=[O:13])=[CH:10][CH:9]=[CH:8][N:7]=1>>[CH:1]1([N:4]2[C:6]3[N:7]=[CH:8][CH:9]=[CH:10][C:11]=3[C:12](=[O:13])[NH:14][C:15]3[C:20]([CH3:21])=[CH:19][CH:18]=[N:17][C:16]2=3)[CH2:3][CH2:2]1

参加物

3

反応物 2

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

生成物 1

HCID 4463Nevirapine収率 83%

反応条件

温度
130 °C

実験手順

287.2 kg of 2-chloro-N-(2-chloro-4-methyl-3-pyridyl)-3-pyridine carboxamide (4), 57.0 kg of calcium oxide and 87.1 kg of cyclopropylamine (molar ratio: 1:1:1.5) are heated in 574 l of diglyme (diethylene glycol-dimethylether) to 135°-145° C. for about 30 minutes in a 1200 l VA stirring apparatus. This produces a pressure of 1.2-1.5 bar and about 50% of the starting material (4) is reacted. To this mixture, over about 30 minutes at 135°-145° C., a further 58.1 kg of cyclopropylamine is added producing a pressure of 3.0-3.5 bar, and another 25% of the starting material (4) is reacted. The mixture is then kept at 135°-145 ° C. for a period of 5 to 6 hours. The reaction mixture is then cooled to a temperature of 20° to 30° C. and filtered. The filter cake is washed with 144 l of diglyme. The filtrates are combined and 400 l of solvent is distilled off. The residue is then diluted with a further 287 l of diglyme. Over 20-40 minutes, the resultant diluted solution is added to a suspension of 110 kg of 60% sodium hydride in 862 l of diglyme, heated to 130° C. The storage vessel and conduits are rinsed with a further 144 l of diglyme and the mixture is stirred at a temperature of 130° to 140° C. for another 30 to 60 minutes. The majority of the diglyme is then distilled off. Finally, the remaining residue is carefully mixed with 1150 l of water. After the reaction mixture has been cooled to a temperature of about 25° C., 575 l of cyclohexane and 147 l of glacial acetic acid are added. The mixture is then stirred for about 1 hour at a temperature of 10°-25° C. The resultant suspension is centrifuged and the centrifuged material is then washed with 575 l of methyl-tert.-butylether, followed by 862 l of water and finally with 575 l of ethanol. In this way, after drying, 225 kg (83.0% 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 obtained.

後処理

  1. customis reacted
  2. customproducing a pressure of 3.0-3.5 bar
  3. waitThe mixture is then kept at 135°-145 ° C. for a period of 5 to 6 hours
  4. temperatureThe reaction mixture is then cooled to a temperature of 20° to 30° C.
  5. filtrationfiltered
  6. washThe filter cake is washed with 144 l of diglyme
  7. distillation400 l of solvent is distilled off
  8. additionThe residue is then diluted with a further 287 l of diglyme
  9. waitOver 20-40 minutes
  10. additionthe resultant diluted solution is added to a suspension of 110 kg of 60% sodium hydride in 862 l of diglyme
  11. washThe storage vessel and conduits are rinsed with a further 144 l of diglyme
  12. distillationThe majority of the diglyme is then distilled off
  13. additionFinally, the remaining residue is carefully mixed with 1150 l of water
  14. temperatureAfter the reaction mixture has been cooled to a temperature of about 25° C., 575 l of cyclohexane and 147 l of glacial acetic acid
  15. additionare added
  16. stirringThe mixture is then stirred for about 1 hour at a temperature of 10°-25° C
  17. washthe centrifuged material is then washed with 575 l of methyl-tert.-butylether
  18. customIn this way, after drying

出典と根拠

ORDレコード
ord-f3cb7b153750429991e6e8d3c0fef850
出典データセット
uspto-grants-1996_10
特許番号
US05569760

関連ノート

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