A Synthetic Entry to Furo[2,3-b]pyridin-4(1H)-ones and Related Furoquinolinones via Iodocyclization

Abstract

N-Methyl-4-alkoxy-3-alkynylpyridin-2(1H)-ones readily undergo iodine-promoted 5-endo-heteroannulation under mild conditions to 3-iodofuropyridinium triiodide salts in moderate to good yields. The latter may be dealkylated in situ upon exposure to an iodide anion to provide the corresponding 3-iodofuro[2,3-b]pyridin-4(1H)-ones. The same strategy applies to the formation of furo[2,3-b]quinolin-4(9H)-ones.

Synthesis of Furo[2,3‐b]pyrazine Nucleoside Analogues with 1,2,3‐Triazole Linkage

“…Finally, we have synthesized 2-chloro-7-iodo-6-phenylfuro[2, 3-b]pyrazine (8) starting from pyrazinone 1a, via microwave-assisted Sonogashira cross-coupling reaction followed by iodocyclization [15] (Scheme 4). Interestingly, the second microwave-assisted Sonogashira cross-coupling reaction with TMSA on furopyrazine 8 proceeded as a sequential self-promoted process without the use of TBAI catalyst, resulting in the disubstituted bisacetylene 9, after further removal of the trimethylsilyl group.…”

De novo Design of SARS-CoV-2 Main Protease Inhibitors

“…Prepared according to a modified literature procedure. 15 A deaerated solution of bromo-pyridone (0.100 mmol), CuI (20 mol%), Pd(PPh3)2Cl2 (20 mol%) and triethylamine (0.200 mmol) in MeCN (1.0 mL) was treated with an alkynyl compound (0.120 mmol) and stirred for an individually specified time (5-20 h) in a sand bath preheated to 60 °C. The mixture was filtrated through a plug of Celite, washed with CH2Cl2 and the filtrate was concentrated in vacuo.…”

Practical One-Pot Syntheses of Regioisomeric Furan-Fused Pyridinones (and Quinolinones) from Common Precursors

“…3-Alkynylpyridin-2-ones 1 and 2 and related quinolin-2ones 3 (Figure 1) are easily prepared from the corresponding iodo precursors using classical Sonogashira crosscoupling procedures. [2][3][4][5] Efficient and reliable protocols are also available to iodinate C3 of 4-alkoxypyridin-2ones and 4-alkoxyquinolin-2-ones on a large scale and in high yields using N-iodosuccinimide. 2,4 Introduction of an aryl moiety at C5 of the pyridin-2-one nucleus may be achieved by regioselective Suzuki cross-coupling reactions of 3,5-diiodopyridin-2-ones with arylboronic acids.…”

“…1 In recent years, our group has demonstrated the synthetic value of diversely halogenated 4-alkoxypyridin-2-one scaffolds as precursors of differently fused furopyridinones via acetylide cross-coupling reactions followed by heteroannulations. [2][3][4][5][6] Herein, we wish to disclose practical, one-step procedures that allow selective access to regioisomeric furopyridinones of type II and III from common 3-alkynyl-4-methoxypyridin-2-one precursors I (Schemes 1 and 2). The procedures may also be applied to the synthesis of linearly or angularly fused furoquinolinones.…”