Synthesis of QUPIC (PB-22)

[WillD]

1-Pentylindole.

1. To a stirred solution of 100 g of indole in 200 ml of DMSO was added 200 g of crushed KOH.
2. Addition of 260 g of 1-bromopentane was followed by stirring at ambient temperature for 1.5 h.
3. The reaction was quenched with water and the product was extracted with 3 portions of dichloromethane
4. The organic layer was dried (MgSO4) and concentrated in vacuo.
5. Distillation at 200 *C under 19 in.Hg gave 163 g (98%) of 1-pentylindole as a green oil.

1-pentyl-(1H-indole)-3-carbonyl chloride.

1. To a solution of 1-pentylindole (100 g) in 1,1,2,2-tetrachloroethane (1000 ml) at 0 *C was added oxalyl chloride (52 ml) with stirring.
2. The mixture was allowed to warm to room temperature over 1h, then heated to 120 *C for 2 h.

QUPIC (1-Pentyl-1H-indole-3-carboxylic acid 8-quinolinyl ester).

1. The 1-pentyl-(1H-indole)-3-carbonyl chloride solution was cooled to room temperature, and then added to 8-quinolinol (88 g) in pyridine (200 ml) at 0*C.
2. The mixture was stirred at room temperature for 20 min.
3. Ethyl acetate was added to this mixture, which was washed with 1M KOH.
4. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed under vacuum.
5. The obtained product was recrystallized from hexane/ethyl acetate to give QUPIC (68 g) as a white solid.

 

[Majestic666]

Can 1-naphthol replace quinoline ?

 

[Gammarayburst]

1-naphthol is an alternative to quinoline sometimes in reactions.
So, you can use 1-naphthol instead of quinoline in your reaction.
But keep in mind it's not always 100% same for replacement. It also depends on what you are doing with it. The results can be different.

 

[HerrHaber]

I am somewhat unsure but out of reading Tihkal on countless occasions, it was fixed in my mind that indole will react on C3 to form an indole-glyoxyl chloride which is one carbonyl longer than what is shown in the diagram.