2,5-Hexanedione → 5-(2,5-Dimethyl-1H-pyrrol-1-yl)-1H-indole

HRID 552947Notes

Reaction equation

HRID 552947 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[CH2:11]([CH2:15][C:16](=O)[CH3:17])[C:12]([CH3:14])=O.C(OCC)(=O)C>C1(C)C=CC=CC=1>[CH3:17][C:16]1[N:1]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][CH:6]=[CH:5]3)[C:12]([CH3:14])=[CH:11][CH:15]=1

Participants

5

Reactant 3

HCID 80352,5-HexanedioneHCID 8857Ethyl AcetateHCID 788675-Aminoindole

Product 1

HCID 100818535-(2,5-Dimethyl-1H-pyrrol-1-yl)-1H-indole

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a 250 mL argon purged round bottom flask containing a magnetic stirbar and a solution of 5-aminoindole (91) (15.00 g, 113 mmol) in anhydrous toluene (50 mL) was added acetonylacetone (25.4 mL, 216 mmol, 1.9 eq). The flask was fitted with a Dean-Stark trap with a 10 mL reservoir filled with toluene. The uppermost portion of the flask and the condensing arm of the trap were wrapped with foil and the reaction vessel placed into an oil bath preheated to a temperature of 125° C. The dark brown solution was allowed to stir under a continuous flow of argon at this temperature for 45 minutes, followed by draining of the trap solvent reservoir. After a total of 4 hours, TLC (5% ethyl acetate, 95% hexanes) revealed the reaction was complete. The reaction was cooled gradually to room temperature overnight. The reaction was poured onto a plug of silica gel and the solvent pulled through by vacuum filtration. The silica was washed with hexanes (200 mL). A white precipitate started to form almost immediately in the filtrate. The silica was washed again with a solution of 6% diethyl ether, 94% hexanes (800 mL). Crystals were collected from both washes, and the filtrates combined. The plug was washed with ether (150 mL) and the filtrate combined with the washes. The combined filtrates were concentrate to afford a brown oil. The oil was purified on the Biotage SP-1 (0-8% ether in hexanes). TLC revealed that all products were identical (white solids) and all products were combined. (Yield: 17.10 g of white solid, compound 92 (72%). 1H NMR (CDCl3) δ: 8.26 (bs, NH), 7.48-7.48 (d, 1H, J=1.2 Hz), 7.46-7.43 (d, 1H, J=8.7 Hz), 7.31-7.29 (t, 1H, J=2.7), 7.04-7.00 (dd, 1H, J=2.1, 8.4), 6.61 (s, 1H), 5.92 (s, 2H), 2.05 (s, 6H). MS-ESI m/z (%): 211 (M+, 100).

Workup

  1. additionTo a 250 mL argon purged round bottom flask containing a magnetic stirbar
  2. customThe flask was fitted with a Dean-Stark trap with a 10 mL reservoir
  3. customthe reaction vessel placed into an oil bath
  4. custompreheated to a temperature of 125° C
  5. additionThe reaction was poured onto a plug of silica gel
  6. filtrationthe solvent pulled through by vacuum filtration
  7. washThe silica was washed with hexanes (200 mL)
  8. customto form almost immediately in the filtrate
  9. washThe silica was washed again with a solution of 6% diethyl ether, 94% hexanes (800 mL)
  10. customCrystals were collected from both washes
  11. washThe plug was washed with ether (150 mL)
  12. concentrationThe combined filtrates were concentrate
  13. customto afford a brown oil
  14. customThe oil was purified on the Biotage SP-1 (0-8% ether in hexanes)

Sources & evidence

ORD record
ord-270e222e3e454d508027981b9b8a985c
Source dataset
uspto-grants-2011_05
Patent number
US07951940B2

Reaction notes

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