Dimethyl 2-(2,4-Diamino-3-cyano-5 H -chromeno[2,3- b ]pyridin-5-yl)malonate

: Dimethyl sulfoxide (DMSO) is widely used as a solvent in organic synthesis and in pharmacology because of its low cost, stability, and non-toxicity. Multicomponent reactions are a powerful synthetic tool for the rapid and efﬁcient construction of complicated molecular frameworks. In this communication, the multicomponent transformation of salicylaldehyde, malononitrile dimer, and dimethyl malonate in DMSO at room temperature was carefully investigated to give dimethyl 2-(2,4-diamino-3-cyano-5 H -chromeno[2,3- b ]pyridin-5-yl)malonate with good yield. The structure of the new compound was established by means of elemental analysis and mass, nuclear magnetic resonance, and infrared spectroscopy. These results concern the efﬁcient multicomponent transformation of salicylaldehyde 1 , 2-aminoprop-1-ene-1,1,3-tricarbonitrile 2 , and dimethyl malonate 3 into the previously unknown dimethyl 2-(2,4-diamino-3-cyano-5 H -chromeno[2,3- b


Introduction
Dimethyl sulfoxide (DMSO) is widely used as a solvent in organic synthesis and in pharmacology because of its low cost, stability, and non-toxicity [1]. However, in the last decade, DMSO has also attracted the attention of scientists as a source of oxygen, carbon, or sulfur in a wide range of organic reactions [2].
Multicomponent reactions (MCRs) are a powerful synthetic tool for the rapid and efficient construction of complicated molecular frameworks [3]. The advantages of MCRs over multistep synthesis include atom-economy and step-efficiency, which also reduce waste generation [4]. MCRs show a very high bond-forming index (BFI), as several nonhydrogen atom bonds are formed in one synthetic transformation [5]. Hence, MCRs are the best instrument for modern organic synthesis.
Chromeno [2,3-b]pyridines are the important classes of heterocyclic compounds from the point of view of medicinal chemistry as well as industry. Depending on the structure, they demonstrate different types of biological activity, such as antimicrobial [6], anticancer [7], antirheumatic [8], antimyopic [9], neuroprotective [10], and hypotensive [11] properties. In addition, chromeno [2,3-b]pyridines are known as inhibitors of the corrosion of mild steel [12]. Thus, the multicomponent synthesis of novel chromeno [2,3-b]pyridines is an important aim for modern organic chemistry.
The BFI (bond forming index) of this process was four, since four new bonds were formed in one stage, namely 2 C-C bonds, 1 C-N, and 1 C-O bonds.
The structure of compound 4 was confirmed by 1 H, 13 C NMR, and IR spectroscopy as well as mass spectrometry data and elemental analysis (Supplementary Materials). Only one set of signals was observed in 1 H and 13 C NMR spectra.
The BFI (bond forming index) of this process was four, since four new bonds were formed in one stage, namely 2 C-C bonds, 1 C-N, and 1 C-O bonds.
The structure of compound 4 was confirmed by 1 H, 13 C NMR, and IR spectroscopy as well as mass spectrometry data and elemental analysis (Supplementary Materials). Only one set of signals was observed in 1 H and 13 C NMR spectra.
Taking into consideration the results of the 1 H NMR monitoring of the reaction of salicylaldehyde, malononitrile dimer, and malonic acid [20], the following mechanism for the multicomponent transformation of salicylaldehyde 1, 2-aminoprop-1-ene-1,1,3-tricarbonitrile 2, and dimethyl malonate 3 was proposed, as shown in Scheme 3. When the reaction in DMSO had finished, water was added to the reaction mixture and the final compound 4 was directly crystallized in pure form. Compound 4 was synthesized with 90% yield.
The BFI (bond forming index) of this process was four, since four new bonds were formed in one stage, namely 2 C-C bonds, 1 C-N, and 1 C-O bonds.
The structure of compound 4 was confirmed by 1 H, 13 C NMR, and IR spectroscopy as well as mass spectrometry data and elemental analysis (Supplementary Materials). Only one set of signals was observed in 1 H and 13 C NMR spectra.
Taking into consideration the results of the 1 H NMR monitoring of the reaction of salicylaldehyde, malononitrile dimer, and malonic acid [20], the following mechanism for the multicomponent transformation of salicylaldehyde 1, 2-aminoprop-1-ene-1,1,3tricarbonitrile 2, and dimethyl malonate 3 was proposed, as shown in Scheme 3.
The first stage of the process was a rapid formation of intermediate 5 with the expulsion of a hydroxide anion [21]. This hydroxide anion instantly catalyzed a rapid cyclization of intermediate 5 into
The melting point was measured with a Gallenkamp melting-point apparatus (Lon don, UK). 1 H and 13 C NMR spectra were recorded in DMSO-d6 with a Bruker AM300 spec trometer (Billerica, MA, USA) at ambient temperature. The IR spectrum was registered with a Bruker ALPHA-T FT-IR spectrometer (Billerica, MA, USA) in KBr pellets. The MS spectrum (EI = 70 eV) was obtained directly with a Kratos MS-30 spectrometer (Manches ter, UK). For elemental analysis, a 2400 Elemental Analyzer (Perkin Elmer Inc., Waltham MA, USA) was used.
The melting point was measured with a Gallenkamp melting-point apparatus (London, UK). 1 H and 13 C NMR spectra were recorded in DMSO-d 6 with a Bruker AM300 spectrometer (Billerica, MA, USA) at ambient temperature. The IR spectrum was registered with a Bruker ALPHA-T FT-IR spectrometer (Billerica, MA, USA) in KBr pellets. The MS spectrum (EI = 70 eV) was obtained directly with a Kratos MS-30 spectrometer (Manchester, UK). For elemental analysis, a 2400 Elemental Analyzer (Perkin Elmer Inc., Waltham, MA, USA) was used.  1)

Conflicts of Interest:
The authors declare no conflict of interest.