Ammonia → (R)-5-(2,5-dimethyl-1H-pyrrol-1-yl)-3-(2-(1-methylpyrrolidin-2-yl)ethyl)-1H-indole

Participants

Reaction Conditions

Reaction Steps

To an argon purged round bottom flask fitted with a magnetic stirbar and containing a solution 144 (210 mg, 0.461 mmol) in anhydrous THF (5 mL) was added lithium aluminum hydride (79 mg, 2.08 mmol). The flask was fitted with a condenser and placed in an oil bath. The reaction was heated to 75° C. and stirred at reflux with an argon flow for 4.5 hrs. The reaction was revealed to be complete by TLC (10% 2M NH3 in MeOH, 90% CH2Cl2) and was cooled gradually to room temperature. The reaction was quenched by the addition of water (0.2 mL), 3N sodium hydroxide (0.3 mL) and water (0.6 mL). The react was filtered through celite and partitioned with ethyl acetate (10 mL). The aqueous layer was extracted twice more with ethyl acetate (2×10 mL). The combined organics were washed with brine, dried over sodium sulfate and concentrated after decanting to afford a brown oil. The product was purified by silica gel column chromatography (1:1 Ethyl acetate/Hexanes to 5% 2M NH3 in MeOH, 95% CH2Cl2) to afford the desired product as a yellow oil, compound 145. Yield: 105 mg (71%). 1H NMR (CDCl3) δ 8.09 (bs, 1H), 7.44-7.43 (d, 1H, J=1.5 Hz), 7.41-7.38 (d, 1H, 8.7 Hz), 7.08 (d, 1H, J=2.1 Hz), 7.03-7.00 (dd, 1H, J=1.8, 8.1 Hz), 5.91 (bs, 2H), 3.49 (s, 1H), 3.15-3.10 (m, 2H), 2.86-2.65 (m, 3H), 2.34 (s, 4H), 2.03 (bs, 6H), 1.90-1.52 (m, 4H). MS-ESI (m/z, %) 322 (M+, 100)

Provenance & Evidence