Unexpected Synthesis of Highly Substituted Indole Derivatives

Abstract

An unexpected synthesis of highly substituted indole derivatives was provided by treating 2-[2-(4-fluorophenyl)-2-oxo-1-phenylethyl]-4-methyl-3-oxo-pentanoic acid phenylamide with aryl hydrazines in the presence of trifluoroacetic acid in tetrahydrofuran.

Keywords:

• Aryl hydrazine
• cyclization
• 1,4-diketone
• hydrazine hydrate
• indole
• 1,2-pyridazine

ACKNOWLEDGMENTS

The authors thank the management of Dr. Reddy's Laboratories Limited for providing facilities to carry out this work and gratefully acknowledge the cooperation extended by all colleagues.

Notes

Notes. ¹H NMR spectra of 6a–l were recorded in DMSO-d₆ at 400 MHz. ¹³C NMR of 6a (DMSO-d₆): δ 21.94, 22.21, 56.45, 93.32, 115.1, 115.4, 120.5, 121.5, 124.7, 125.6, 126.1, 127.6, 127.8, 127.9, 128.1, 128.2, 128.35, 128.53, 129.4, 131.5, 133.9, 134.0, 136.0, 145.0, 153.0, 158,160.0, 163.0, 167.0, 181.0. DEPT of 6a (DMSO-d₆): CH₃ carbons at δ 21.94, 22.21; CH carbons at δ 115.0–130.0; CH₂ carbons are not observed.

^a Recrystallized from ethanol.

^b Recrystallized from ethanol/H₂O (8:2).

^c Recrystallized from ethyl acetate/n-hexane (1:1).

^d Recrystallized from petroleum ether/isopropyl alcohol (1:1).

^e Recrystallized from ethyl acetate or ethanol.