Uses
3-Cyclohexyl-1H-indole-6-carboxylic Acid is used as a reactant in the preparation of dibenzo[b,f][1,4]thiazepinecarboxamides as hepatitis B core protein modulators.
Synthesis
Step 2: Synthesis of methyl-3-cyclohexyl-1H-indole-6-carboxylate; 3-cyclohexenyl-1H-indole-6-carboxylic acid (from step 1) was dissolved in a THF/MeOH solvent mixture (0.5M, 1:1, v/v) with the addition of a Pd(OH)2/C catalyst (0.1 equiv, 20%). Hydrogenation was carried out at 60 psi hydrogen pressure for 14 hours. Upon completion of the reaction, the catalyst was removed by filtration through a diatomaceous earth pad. The filtrate was concentrated to dryness to afford 3-cyclohexyl-1H-indole-6-carboxylic acid in 90% yield as a white solid.1H NMR (300 MHz, DMSO-d6, 300 K) δ 1.20-1.53 (m, 5H), 1.70-1.87 (m, 3H), 1.90-2.02 (m, 2H), 2.69-2.86 (m, 1H), 7.40 (s, 1H), 7.55-7.65 (m, 2H), 8.0 (s, 1H), 11.40 (s, 1H); MS (ES+) m/z 244 (M + H)+. The above product was dissolved in MeOH (0.4 M) and thionyl chloride (0.5 eq.) was added dropwise at 0 °C and then refluxed for 24 hours. After completion of the reaction, volatiles were removed by distillation under reduced pressure to afford methyl-3-cyclohexyl-1H-indole-6-carboxylate in 100% yield as a solid.
References
[1] Patent: WO2006/29912, 2006, A1. Location in patent: Page/Page column 21-22
[2] Patent: WO2009/147121, 2009, A1. Location in patent: Page/Page column 65-66
[3] Patent: WO2009/80836, 2009, A2. Location in patent: Page/Page column 56
[4] Patent: WO2006/76529, 2006, A1. Location in patent: Page/Page column 135
[5] Patent: US2007/78122, 2007, A1. Location in patent: Page/Page column 174
