Indium(III) Chloride Catalyzed Convergent, Regioselective Synthesis of Annulated Quinoline and Pyridine Derivatives

Abstract

A direct convergent two-component regioselective synthesis of annulated pyridine motif from 1-aminopenta-1,4-diene fragment and aromatic aldehyde by indium(III) chloride catalyzed reaction has been developed through a concerted pathway. A series of potentially bioactive pyranoquinoline, phenanthroline, and pyridopyrimidine derivatives has been synthesized in high yields by this protocol.

Key words

indium(III) chloride - imine - Lewis acid - concerted ­reaction - electrocyclization - pyranoquinoline - phenanthroline - pyridopyrimidine

References and Notes

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27

Procedure for the Preparation of Compound 3a A mixture of 5-allyl-6-amino-2H-chromen-2-one (1a, 200 mg, 0.995 mmol, 1.0 equiv) and benzaldehyde (2a, 105.5 mg, 0.995 mmol, 1.0 equiv) was stirred in toluene at r.t.
for 10 min. After addition of InCl₃ (21.9 mg, 0.0995 mmol, 0.1 equiv), the reaction mixture was refluxed for 6.5 h (completion of the reaction was monitored by TLC).
The reaction mixture was cooled and to avoid any further workup, the mixture was directly dry packed over a silica gel (230-400 mesh) column. The pure product was obtained by eluting the column with PE-EtOAc mixture (4:1). The pure product thus obtained was recrystallized from MeCN to give compound 3a as white powder with an isolated yield of 93%; mp 240 ˚C. IR (KBr): 2924, 2853, 1728 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 2.57 (s, 3 H, CH₃), 6.63 (d, 1 H, J = 10.0 Hz, ArH), 7.47-7.54 (m, 3 H, ArH), 7.60-7.66 (m, 3 H, ArH), 8.28 (d, 1 H, J = 9.2 Hz, ArH), 8.40 (s, 1 H, ArH), 8.46 (d, 1 H, J = 9.6 Hz) ppm. ^¹³C NMR (100 MHz, CDCl₃): δ = 21.2, 112.1, 116.2, 119.8, 123.4, 128.5, 128.6, 128.9, 130.8, 131.4, 134.4, 138.4, 140.0, 143.7, 153.6, 160.3, 160.7 ppm. HRMS (ES⁺): m/z calcd for C₁₉H₁₃NO₂ [M + H]: 288.0017; found: 287.9302.

29

Procedure for the Preparation of Compound 5a A mixture of 6-allyl-5-amino-1,3-dimethylpyrimidine-2,4 (1H,3H)-dione 4 (200 mg, 1.02 mmol), benzaldehyde (2a, 108.1 mg, 1.02 mmol) was stirred in toluene at r.t. for 10 min. After addition of indium(III) chloride (22.5 mg, 0.102 mmol), the reaction mixture was refluxed for 6.5 h (the completion of the reaction was monitored by TLC). The reaction mixture was cooled and to avoid any further workup, the mixture was dry packed over a silica gel (230-400 mesh) column. The pure product was obtained by eluting the column with a PE-EtOAc mixture (1:1). The product thus obtained was recrystallized from MeCN to give compound 5a as white powder. Yield: 91%; mp 218-220 ˚C. IR (KBr): 2948, 1714, 1666, cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 2.51 (s, 3 H, CH₃), 3.54 (s, 3 H, NCH₃), 3.64 (s, 3 H, NCH₃), 7.41-7.48 (m, 4 H, ArH), 7.45-7.56 (m, 2 H, ArH), ppm. ^¹³C NMR (100 MHz, CDCl₃): δ = 21.1 (CH₃), 29.0, 30.6, 123.6, 128.2, 128.4, 129.3, 129.8, 136.6, 137.9, 138.8, 150.8, 155.3, 160.7 ppm. ESI-HRMS: m/z calcd for C₁₆H₁₅N₃O₂ [M + H]⁺: 282.1250; found: 282.1237.