Tetrahydrofuran → Israpafant

HRID 620183Notes

Reaction equation

HRID 620183 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]2[CH:19]=[C:18]([CH2:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([CH2:28][CH:29]([CH3:31])[CH3:30])=[CH:24][CH:23]=3)[S:17][C:10]=2[NH:11][C:12](=S)[CH:13]([CH3:15])[N:14]=1.O.[NH2:33][NH2:34].O1[CH2:39][CH2:38]CC1>>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]2[CH:19]=[C:18]([CH2:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([CH2:28][CH:29]([CH3:31])[CH3:30])=[CH:24][CH:23]=3)[S:17][C:10]=2[N:11]2[C:38]([CH3:39])=[N:33][N:34]=[C:12]2[CH:13]([CH3:15])[N:14]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 24654Hydrazine hydrate (1:1)HCID 135415188HCID 135415188, compound

Product 1

HCID 119175Israpafant

Procedure

To a solution of 9.1 g of 5-(2-chlorophenyl)-7-[2-(4-isobutylphenyl)ethyl]-3-methyl-1,3-dihydro-2H-thieno[2,3-e]-1,4-diazepine-2-thione in 150 ml of tetrahydrofuran is added 3.1 g of 100% hydrazine hydrate under ice-cooling and the mixture is stirred at room temperature for 2 hours. After the tetrahydrofuran is distilled off under reduced pressure, the residue is dissolved in 200 ml of chloroform and the solution is dried over anhydrous magnesium sulfate. After separating by filtration, the filtrate is concentrated under reduced pressure. To the residue is added 50 ml of ethyl orthoacetate and the mixture is heated at 70°-72° C. for an hour. The mixture is concentrated under reduced pressure, and the residue is subjected to chromatography on silica gel and eluted with chloroform-methanol (100:1 to 100:3) solvent. The eluate of the objective fraction is concentrated and the residue is crystallized from isopropyl ether to give 4.3 g of 4-(2-chlorophenyl)-2-[2 -(4-isobutylphenyl)ethyl]-6,9-dimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine as colorless crystals, melting at 129.5°-131.5° C.

Workup

  1. temperaturecooling
  2. distillationAfter the tetrahydrofuran is distilled off under reduced pressure
  3. dissolutionthe residue is dissolved in 200 ml of chloroform
  4. dry with materialthe solution is dried over anhydrous magnesium sulfate
  5. customAfter separating by filtration
  6. concentrationthe filtrate is concentrated under reduced pressure
  7. additionTo the residue is added 50 ml of ethyl orthoacetate
  8. temperaturethe mixture is heated at 70°-72° C. for an hour
  9. concentrationThe mixture is concentrated under reduced pressure
  10. washeluted with chloroform-methanol (100:1 to 100:3) solvent
  11. concentrationThe eluate of the objective fraction is concentrated
  12. customthe residue is crystallized from isopropyl ether

Sources & evidence

ORD record
ord-684b03a67c4e44189e026612892096cf
Source dataset
uspto-grants-1989_04
Patent number
US04820703

Reaction notes

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