Crystal structure of 2,4-diamino-5-(4-hydroxy-3-methoxyphenyl)-8,8-dimethyl-6-oxo-6,7,8,9-tetrahydro-5H-chromeno[2,3-b]pyridine-3-carbonitrile–dimethylformamide–water (1/1/1)

The heterocyclic system of the title compound is approximately planar except for the carbon atom of the CMe2 group; the residues are connected by extensive classical hydrogen bonding.

In the structure of the title compound, C 22 H 22 N 4 O 4 •C 3 H 7 NO•H 2 O, the entire tricyclic system is approximately planar except for the carbon atom bearing the two methyl groups; the methoxyphenyl ring is approximately perpendicular to the tricycle.All seven potential hydrogen-bond donors take part in classical hydrogen bonds.The main molecule and the DMF combine to form broad ribbons parallel to the a axis and roughly parallel to the ab plane; the water molecules connect the residues in the third dimension.

Chemical context
Activated nitriles and �,�-unsaturated nitrile moieties are involved in a wide variety of natural plant products, drugs, colourants and agrochemicals (Fleming & Wang, 2003;Ahmed et al., 2022); they also represent versatile starting materials for the synthesis of a wide variety of therapeutically important heterocycles (Zhang et al., 2019;Metwally et al., 2023).The generally accepted importance of these functions (Wang et al., 2016;Hebishy et al., 2023) is reflected in the investment of much effort to synthesize them (Zhang et al., 2023;Elgemeie et al., 1998a,b).Recently, we have reported several new methods for the synthesis of pharmaceutically relevant heterocycles utilizing activated nitriles and �,�-unsaturated nitriles as starting materials (e.g.Mohamed-Ezzat et al., 2021).In this context, we and others have synthesized several condensed carbocyclic pyrans and carbocyclic pyridines using dimedone as the starting material (Hebishy et al., 2022;Tu et al., 2014).
The present investigation reports a new one-pot synthesis of condensed carbocyclic pyridines by the reaction of dimedone with enamino nitriles.It was found that 2-aminoprop-1-ene-1,1,3-tricarbonitrile (1) reacted with 4-hydroxy-3-methoxybenzaldehyde (2) and dimedone (4) in refluxing n-butanol containing catalytic amounts of trimethylamine to give the corresponding condensed chromeno[2,3-b]pyridine-3-carbonitrile (7) (Fig. 1).The structure of 7 was confirmed on the basis of elemental analysis and spectroscopic studies ( 1 H NMR, IR and MS).We suggest that the formation mechanism of 7 from 1, 2 and 4 involves a condensation reaction that consists of an initial Michael addition of the methylene group of the dimedone 4 to the double bond of intermediate 3 to give the next intermediate 5, which then cyclizes to the condensed chromeno[2,3-b]pyridine-3-carbonitrile 7.In order to establish the structure of the compound unambiguously, the crystal structure was determined and is presented here.

Structural commentary
The structure of the product 7, which crystallized from DMF as a 1/1/1 adduct with DMF and water, is shown in Fig. 2. Molecular dimensions, a selection of which are given in Table 1, may be regarded as normal (e.g. the double-bond length C5A C9A).The pyridinic ring is planar, and its direct substituents also lie in the same plane (r.m.s.deviation of eleven atoms = 0.008 A ˚); the angle between this plane and that of the methoxyphenyl ring is 77.86 (2) � .The atoms C5A and C9A lie 0.317 (1) and 0.249 (1) A ˚, respectively, out of the plane in the same direction.The central ring has the form of a flattened boat, with C5 and O10 lying 0.166 (1) and 0.101 (1) A ˚, respectively, out of the plane of the other four atoms (r.m.s.deviation = 0.015 A ˚).The third ring of the tricyclic system, formally related to cyclohexen-2-one, has the expected envelope form, in which the atom C8 lies 0.673 (1) A out of the plane of the other five atoms (r.m.s.deviation 0.029 A ˚). Viewed from the side (Fig. 3), it can be seen that the entire tricyclic system is approximately planar (r.m.s.deviation 0.14 A ˚) except for C8.

Supramolecular features
All seven of the potential hydrogen-bond donors do indeed take part in classical hydrogen bonds (Table 2), although the contact N4-H03� � �O98 is appreciably longer than the others, and O99-H07 is part of a three-centre system with N1 and the more distant O10 as acceptors.There is also one short linear contact involving a phenyl hydrogen, C22-H22� � �O98, research communications Acta Cryst. (2024).E80, 396-400 The reaction scheme for the synthesis of compound 7.

Figure 2
The structure of compound 7 (as its 1/1/1 adduct with DMF and water) in the crystal.Ellipsoids correspond to 50% probability levels.The dashed lines indicate hydrogen bonds.
Side view of compound 7 (hydrogen atoms excluded).
which may be considered as a weak hydrogen bond; this is, however, not represented in the Figures for clarity reasons.
The molecules of 7 and the DMF combine to form broad ribbons parallel to the a axis (Fig. 4), in which inversionsymmetric R 2 2 (12) rings, based on the hydrogen bond N4-H04� � �N3, are prominent.The DMF molecules project above and below the planes of the ribbons.The water molecules connect the residues in the third dimension (Fig. 5).They accept one hydrogen bond and act as donor for three hydrogen bonds (counting both branches of the three-centre system).

Database survey
The search employed the routine ConQuest (Bruno et al., 2002), part of Version 2022.3.0 of the Cambridge Database (Groom et al., 2016).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. Hydrogen atoms bonded to nitrogen or oxygen were refined freely.The methyl groups were included as an idealized rigid group allowed to rotate but not tip (command AFIX 137), with C-H = 0.99 A ˚and H-C-H = 109.5� .Other hydrogen atoms were included using a riding model starting from calculated positions (C-H methylene = 0.99, C-H methine = 1.00,C-H arom = 0.95 A ˚).The U(H) values were fixed at 1.5 � U eq of the parent carbon atoms for the methyl groups and 1.2 � U eq for other hydrogens.Three reflections, with intensities clearly in error, were omitted.The largest peaks of residual electron density (max.0.67 e A ˚À 3 ) lie in the middle of bonds and thus do not give cause for concern.(Sheldrick, 2015b) and XP (Bruker, 1998).

398Figure 4
Figure 4Packing diagram of compound 7 (including the DMF molecules, which are seen edge-on), showing two broad ribbons running vertically.The methoxyphenyl rings are reduced to the ipso atoms C21 for clarity.Hydrogen atoms not involved in hydrogen bonding are also omitted.View direction: perpendicular to the ab plane.Hydrogen bonds are shown as dashed lines (thin for the longer bonds N4-H03� � �O98, otherwise thick).

Figure 5
Figure 5 Packing diagram of compound 7, with view direction approximately perpendicular to (101), showing the role of the water molecules.Hydrogen bonds involving these molecules are shown as thick dashed bonds, other hydrogen bonds as thin dashed bonds.

Table 3
Experimental details.