(6bR,10aS)-3-Methyl-2,3,6b,7,8,9,10,10a-octahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxaline Chemical Properties

Boiling point:

374.5±42.0 °C(Predicted)

Density 

1.23±0.1 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2–8 °C

form 

Solid

pka

10.30±0.20(Predicted)

(6bR,10aS)-3-Methyl-2,3,6b,7,8,9,10,10a-octahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxaline Usage And Synthesis

Uses

IHCH-7113 (Compound 166) is an agonist of 5-HT2A serotonin receptor with antidepressant activity. IHCH-7113 is promising for research of antipsychotic agent[1].

Synthesis

Example 8: Preparation of (6bR,10aS)-3-methyl-2,3,6b,7,8,9,10,10a-octahydro-1H-pyrido[3',4': 4,5]pyrrolo[1,2,3-de]quinoxaline: tert-butyl (6bR,10aS)-3-methyl-2,3,6b,7,10,10a-hexahydro-1H-pyrido[3',4'. 4,5]pyrrolo[1,2,3-de]quinoxaline-8-carboxylic acid tert-butyl ester (ca. 18.5 g, 57 mmol), KOH (12.7 g, 226 mmol), and n-butanol were added to a 300 mL pressurized flask and heated at 120 °C in an oil bath for 3 hours. Upon completion of the reaction, n-butanol was removed under reduced pressure and 300 mL of water was added, followed by extraction with dichloromethane (DCM). The DCM layers were combined, washed with brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give (6bR,10aS)-3-methyl-2,3,6b,7,8,9,10,10a-octahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxaline. Alternative method: tert-butyl (6bR,10aS)-3-methyl-2,3,6b,7,10,10a-hexahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxaline-8-carboxylate and 1090 mL of HCl were added to a 5L three-necked, round-bottomed flask. the resultant solution was heated at 95°C for 15 hours. Upon completion of the reaction, the reaction mixture was cooled to about 50 °C in an ice bath, followed by the addition of 1090 mL of methyl tert-butyl ether (MTBE). A 25% NaOH solution (1308 mL) was slowly added through the addition funnel, keeping the internal temperature below 30°C. After addition of the NaOH solution, the aqueous layer was pH > 14. 1090 mL of ethyl acetate (EtOAc) was added and the resulting dark-colored mixture was stirred in an ice bath for about 1 hour. The layers were separated and the aqueous layer was extracted with 1090mL EtOAc. The organic layers were combined, washed with 1090 mL of brine, filtered, and concentrated under reduced pressure to give 166.8 g of dark brown liquid (theoretical yield 158.5 g).HPLC analysis showed the product to be 88.1% pure.1H NMR analysis conformed to the expected structure, showing the presence of more than 5% of a single impurity.LC-MS analysis showed 93% of the main peak m/e=230 (M+1). The product was stored in a cold room under N2 protection.1H NMR (CDCl3,300MHz) δ 1.71-1.97 (m,2H), 2.58-2.70 (m,1H), 2.80-2.92 (m,6H), 2.98-3.12 (m,2H), 3.26-3.37 (m,3H), 3.55-3.44 (m,1H) , 6.41 (d,J=7.8Hz,1H), 6.51 (d,J=7.2Hz,1H), 6.65 (t,J=7.8Hz,1H).

References

[1] Duan W, et al. Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants. Chem Rev. 2024 Jan 10;124(1):124-163. DOI:10.1021/acs.chemrev.3c00375