Hexahydro-1,4-diazepine → Fasudil

HRID 1585975

Reaktionsgleichung

Reaktionsgleichung von HRID 1585975
[CH:1]1[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([S:11](Cl)(=[O:13])=[O:12])[C:5]=2[CH:4]=[CH:3][N:2]=1.[NH:15]1[CH2:21][CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1>C(Cl)(Cl)Cl>[CH:8]1[CH:9]=[C:10]2[C:5](=[C:6]([S:11]([N:15]3[CH2:16][CH2:17][NH:18][CH2:19][CH2:20][CH2:21]3)(=[O:13])=[O:12])[CH:7]=1)[CH:4]=[CH:3][N:2]=[CH:1]2

Komponenten

4

Edukt 2

HCID 68163Hexahydro-1,4-diazepineHCID 33716555-Isoquinolinesulfonyl chloride

Produkt 1

HCID 3547FasudilAusbeute 93,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6212ChloroformLösungsmittel2×

Versuchsvorschrift

40 liters of a chloroform solution containing 5.0 kg of 5-isoquinolinesulfonyl chloride was added dropwise to 40 liters of a chloroform solution containing 8.8 kg of homopiperazine over 1 hour while cooling with ice, to obtain a mixture. Subsequently, the obtained mixture was stirred for 1 hour while cooling with ice, to effect a reaction and then the resultant reaction mixture was subjected to extraction with a 2N aqueous solution of HCl, followed by separation of an aqueous phase. The aqueous phase was adjusted to a pH value of 10 with a 10% aqueous solution of NaOH to thereby obtain a solution having a pH value of 10. The obtained solution was subjected to extraction with 80 liters of chloroform, followed by separation of a chloroform phase. The resultant chloroform phase was washed with water and then dried over anhydrous sodium sulfate, and subsequently, the solvent was removed by distillation under reduced pressure to obtain a residue. The obtained residue was subjected to column chromatography using 150 kg of silica gel (Wakogel C-200, manufactured and sold by Wako Pure Chemical Industries, Ltd., Japan) and a mixed solvent of methanol and chloroform (5 v/v % methanol) as a developing solvent, and purified to obtain 6.01 kg of fasudil (yield 89%). The results of elemental analysis of fasudil: found (calculated) C: 57.59 (57.71), H: 5.92 (5.88), N: 14.29 (14.42), S: 10.83 (11.00) (wt %)

Aufarbeitung

  1. temperaturewhile cooling with ice
  2. customto obtain a mixture
  3. temperaturewhile cooling with ice
  4. customa reaction
  5. customthe resultant reaction mixture
  6. extractionwas subjected to extraction with a 2N aqueous solution of HCl
  7. customfollowed by separation of an aqueous phase
  8. customto thereby obtain a solution
  9. extractionThe obtained solution was subjected to extraction with 80 liters of chloroform
  10. customfollowed by separation of a chloroform phase
  11. washThe resultant chloroform phase was washed with water
  12. dry with materialdried over anhydrous sodium sulfate
  13. customsubsequently, the solvent was removed by distillation under reduced pressure
  14. customto obtain a residue
  15. customa mixed solvent of methanol and chloroform (5 v/v % methanol) as a developing solvent, and purified

Quellen und Nachweise

ORD-Eintrag
ord-710bf8f16e504e278c5796867f88f845
Quelldatensatz
uspto-grants-1999_08
Patentnummer
US05942505

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