A Novel One-Pot, Two-Step Reaction for the Synthesis of Indenopyrrolo[3,2-c]pyridinone Derivatives with a Recyclable Catalyst

Abstract

An efficient strategy was developed for the synthesis of indenopyrrolopyridinone derivatives from 4-hydroxy-6-methyl-2H-pyran-2-one, an amine, and 2,2-dihydroxy-1H-indene-1,3(2H)-dione by a one-pot, two-step, four-component process. The one-pot reaction gives various substituted indenopyrrolopyridinones in good yields and uses a solid acid as a recyclable catalyst in water. This procedure has the advantages of inexpensive substrates, a reusable solid-supported catalyst, and a convenient one-pot operation.

Key words

multicomponent reaction - one-pot reaction - hydroxy­methylpyranonone - amines - dihydroxyindenedione - indenopyrrolopyridinones

• References and Notes

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• 17 2,5-Disubstituted 5a,10a-Dihydroxy-3-methyl-2,5,5a,10a-tetrahydroindeno[2′,1′:4,5]pyrrolo[3,2-c]pyridine-1,10-diones 5a–l; General Method A mixture of pyranone 1 (0.5 mmol), the appropriate amine 2 (1.0 mmol), and solid acid (10 mg) in H₂O (3.0 mL) in sealed tube was heated at 80 °C until starting material was completely converted (~2 h; TLC). Indenedione 4 (0.5 mmol) was then added and the mixture was heated at 80 °C for another 4 h. The mixture was cooled to r.t. and the solid product was collected by filtration and washed with H₂O. The crude product and solid acid were treated with hot 95% EtOH. The catalyst was removed by filtration, and the pure product 5 was obtained from the mother liquor. 5a,10a-Dihydroxy-3-methyl-2,5-diphenyl-2,5,5a,10a-tetrahydroindeno[2′,1′:4,5]pyrrolo[3,2-c]pyridine-1,10-dione (5a) Yellow crystals; yield: 177.0 mg (81%); mp 238–240 °C. IR (KBr): 3403, 1721, 1638, 1487, 1454, 1357, 1197, 1021, 943, 870, 772 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.85–7.86 (m, 1 H, ArH), 7.39–7.52 (m, 10 H, ArH), 7.20–7.23 (m, 1 H, ArH), 7.11–7.14 (m, 1 H, ArH), 6.78 (dd, J = 5.6, 2.8 Hz, 1 H, ArH), 6.41 (br s, 1 H, OH), 5.63 (s, 1 H, CH), 5.36 (s, 1 H, OH), 1.83 (s, 3 H, CH₃). ¹³C NMR (100 MHz, CDCl₃): δ = 197.3, 161.2, 155.9, 150.7, 147.7, 138.3 (2 C), 136.9, 135.2 (2 C), 135.0, 129.9, 129.4, 128.8, 128.7, 128.5, 128.4, 127.8 (2 C), 124.9, 124.5, 100.2, 96.2, 93.4, 82.7, 77.3, 22.5. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₇H₂₁N₂O₄ ⁺: 437.1496; found: 437.1495.
• 18 5-Aryl-5a,10a-dihydroxy-3-methyl-5a,10a-dihydro-1H-indeno[1,2-b] pyrano[3,4-d]pyrrole-1,10(5H)-diones 7a–d; General Procedure A mixture of pyranone 1 (0.5 mmol), the appropriate amine 2 (0.5 mmol), and solid acid (10 mg) in water (3.0 mL) in a sealed tube was stirred at r.t. until the starting material was completely converted (~12 h; TLC). Indenedione 4 (0.5 mmol) was then added and the mixture was heated at 80 °C for another 4 h. The mixture was cooled to r.t. and the solid product was collected by filtration and washed with H₂O. The crude product and the solid acid were treated with hot 95% EtOH and water. The catalyst was removed by filtration, and the pure product 7 was obtained from the mother liquor. 5a,10a-Dihydroxy-5-(4-methoxyphenyl)-3-methyl-5a,10a-dihydro-1H-indeno[1,2-b]pyrano[3,4-d]pyrrole-1,10(5H)-dione (7a) Gray solid; yield: 147.2 mg (75%); mp 286–288 °C. IR (KBr): 3401, 1720, 1637, 1488, 1451, 1356, 1149, 1028, 875, 758 cm^–1. ¹H NMR (400 MHz, DMSO-d₆ ): δ = 7.60 (d, J = 7.2 Hz, 1 H, ArH), 7.53–7.63 (m, 2 H, ArH), 7.38 (s, 1 H, OH), 7.20 (d, J = 8.0 Hz, 2 H, ArH), 7.07 (d, J = 8.8 Hz, 2 H, ArH), 6.73 (d, J = 7.6 Hz, 1 H, ArH), 6.36 (s, 1 H, OH), 5.59 (s, 1 H, CH), 3.83 (s, 3 H, OMe), 2.06 (s, 3 H, CH₃). ¹³C NMR (100 MHz, DMSO-d₆ ): δ = 197.4, 167.4, 159.4, 158.5, 158.2, 147.7, 135.7 (2 C), 135.0, 130.8, 128.4 (2 C), 125.6 (2 C), 123.8, 114.9, 97.1, 93.1, 91.4, 83.1, 55.8, 20.4. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₂H₁₈NO₆ ⁺: 392.1129; found: 392.1131