Hydrochloric Acid → Olanzapine

HRID 1782401Notes

Reaction equation

HRID 1782401 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[C:9](=[CH:26][CH2:27][CH3:28])[C:10](N3CCN(C)CC3)=[N:11][C:12]3[CH:18]=[CH:17][CH:16]=[CH:15][C:13]=3[N:14]=2)[CH2:4][CH2:3]1.[S].C(N(CC)CC)C.Cl.C[S:39](C)=O>C(O)CC.ClCCl>[CH3:28][C:27]1[S:39][C:10]2[NH:11][C:12]3[CH:18]=[CH:17][CH:16]=[CH:15][C:13]=3[N:14]=[C:8]([N:5]3[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]3)[C:9]=2[CH:26]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 5362487SulfurHCID 102492283H-1,5-Benzodiazepine, 2,4-bis(4-methyl-1-piperazinyl)-3-propylidene-

Product 1

HCID 135398745OlanzapineYield 12%

Reagents, catalysts & solvents 2

HCID 10311-PropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 2,4-bis(4-methyl-1-piperazinyl)-3-propylidene-3H-[1,5]benzodiazepine (11.90 g, 31.3 mmol), sulphur (20.07 g, 626 mmol) and triethyl amine (4.34 ml, 31.3 mmol) in dimethyl sulfoxide (100 ml) and 1-propanol (100 ml) was heated at 100° C. for five days. The resulting black suspension was cooled and filtered off and the filtrate was evaporated at reduced pressure to obtain a viscous black oil. Dichloromethane (600 ml) and HCl (0.2 M, 600 ml) were added and the phases were separated. The organic phase was extracted again with HCl (0.5 M, 100 ml). The combined water phases were made alkalic at a pH of 9 to 10. Dark brown precipitate was filtered off. Dichloromethane (250 ml) was added to the filtrate. The phases were separated and the water phase was extracted with dichloromethane (2×60 ml). The organic phase was dried over anhydrous Na2SO4 and the solvent was evaporated at reduced pressure. The black oil was combined with precipitate and purified by chromatography on silica gel, eluted with ethyl acetate/triethylamine 50/1 to obtain 1.195 g (12%) of the title product.

Workup

  1. temperatureThe resulting black suspension was cooled
  2. filtrationfiltered off
  3. customthe filtrate was evaporated at reduced pressure
  4. customto obtain a viscous black oil
  5. customthe phases were separated
  6. extractionThe organic phase was extracted again with HCl (0.5 M, 100 ml)
  7. filtrationDark brown precipitate was filtered off
  8. additionDichloromethane (250 ml) was added to the filtrate
  9. customThe phases were separated
  10. extractionthe water phase was extracted with dichloromethane (2×60 ml)
  11. dry with materialThe organic phase was dried over anhydrous Na2SO4
  12. customthe solvent was evaporated at reduced pressure
  13. custompurified by chromatography on silica gel
  14. washeluted with ethyl acetate/triethylamine 50/1

Sources & evidence

ORD record
ord-9507b3ebe976448097f8f383c6174f7a
Source dataset
uspto-grants-2009_03
Patent number
US07498433B2

Reaction notes

Loading…