Anisole → 4H-Thieno(3,4-b)(1,4)benzodiazepine, 9-(4-methyl-1-piperazinyl)-

HRID 1855727Notes

Reaction equation

HRID 1855727 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.C1(OC)C=CC=CC=1.[CH:16]1[S:17][CH:18]=[C:19]2[C:25]=1[NH:24][C:23](=O)[C:22]1[CH:27]=[CH:28][CH:29]=[CH:30][C:21]=1[NH:20]2.[OH-].[NH4+]>[Ti](Cl)(Cl)(Cl)Cl.CC(O)C.C1(C)C=CC=CC=1>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:23]2[C:22]3[CH:27]=[CH:28][CH:29]=[CH:30][C:21]=3[NH:20][C:19]3=[CH:18][S:17][CH:16]=[C:25]3[N:24]=2)[CH2:4][CH2:3]1

Participants

8

Reactant 4

HCID 7519AnisoleHCID 14923Ammonium HydroxideHCID 531671-Methylpiperazine2×HCID 12482555HCID 12482555, compound

Product 1

HCID 30577014H-Thieno(3,4-b)(1,4)benzodiazepine, 9-(4-methyl-1-piperazinyl)-

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 1140TolueneSolvent2×HCID 3776IsopropanolSolvent

Procedure

To a mixture of 15.0 g. of N-methylpiperazine, 6.3 g. of titanium tetrachloride and 7 ml. of anisole in 67 ml. of toluene is added a mixture of 7.6 g. of N-methylpiperazine and 7.1 g. of 4H-thieno[3,4-b][1,4]benzodiazepin-9(10H)-one in 7 ml. of toluene. This mixture is stirred and refluxed for 2 hours, cooled and 11 ml. of 2-propanol, 5 g. of diatomaceous earth and 10.2 ml. of ammonium hydroxide are added. The mixture is filtered and the solid washed with toluene. The toluene filtrate and washings are washed with water, the toluene layer is separated and extracted with three 150 ml. portions of 3 N hydrochloric acid. The acidic extracts are combined, cooled, made alkaline with ammonium hydroxide and extracted with dichloromethane. This extract is dried, filtered, evaporated to 75 ml. and filtered through magnesium silicate. This filtrate is evaporated giving 9-(4-methyl-1-piperazinyl)-4H-thieno[3,4-b][1,4 ]benzodiazepine.

Workup

  1. additionTo a mixture of 15.0 g
  2. additiona mixture of 7.6 g
  3. temperaturerefluxed for 2 hours
  4. temperaturecooled
  5. filtrationThe mixture is filtered
  6. washthe solid washed with toluene
  7. washThe toluene filtrate and washings are washed with water
  8. customthe toluene layer is separated
  9. extractionextracted with three 150 ml
  10. temperaturecooled
  11. extractionextracted with dichloromethane
  12. customThis extract is dried
  13. filtrationfiltered
  14. customevaporated to 75 ml
  15. filtrationand filtered through magnesium silicate
  16. customThis filtrate is evaporated

Sources & evidence

ORD record
ord-0fee861e547c48c7afae23e807d8ff7c
Source dataset
uspto-grants-1980_08
Patent number
US04216148

Reaction notes

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