Structural, Hirshfeld surface and molecular docking studies of a new organotin(IV)-phosphoric triamide complex and an amidophosphoric acid ester proposed as possible SARS-CoV-2 and Monkeypox inhibitors.

Phosphoramides and their complexes are attractive compounds due to their significant inhibiting functionality in biological medicine. In this paper, a novel organotin(IV)-phosphoramide complex (Sn(CH3)2Cl2{[(3-Cl)C6H4NH]P(O)[NC4H8O]2}2, 1), derived from a reaction between phosphoric triamide ligand with dimethyltin dichloride, and a new amidophosphoric acid ester ([OCH2C(CH3)2CH2O]P(O)[N(CH3)CH2C6H5], 2), prepared from the condensation of a cyclic chlorophosphate reagent with N-methylbenzylamine, are structurally characterized and in silico investigated as potential SARS-CoV-2 and Monkeypox inhibitors by molecular docking simulation. Both compounds crystallize in the monoclinic crystal system with space group P21/c. The asymmetric unit of the complex 1 consists of one-half molecule, where SnIV is located on an inversion center, while the asymmetric part of 2 consists of one whole molecule. In the complex 1, the tin atom adopts a six-coordinate octahedral geometry with trans groups of (Cl)2, (CH3)2 and (PO)2 (PO = phosphoric triamide ligand). The molecular architecture consists of the N-H⋯Cl hydrogen bonds stretching as a 1D linear arrangement along the b axis with intermediate R22(12) ring motifs, whereas in the case of 2, the crystal packing is devoid of any classical hydrogen bond interaction. Furthermore, a graphical analysis by using Hirshfeld surface method identifies the most important intermolecular interactions being of the type H⋯Cl/Cl⋯H (for 1) and H⋯O/O⋯H (for 1 and 2), covering the hydrogen bond interactions N-H⋯Cl and C-H⋯O═P, respectively, which turn out to be favoured. A biological molecular docking simulation on the studied compounds provides evidence to suggest a significant inhibitory potential against SARS-COV-2 (6LU7) and Monkeypox (4QWO) especially for 6LU7 with a binding energy around -6 kcal/mol competing with current effective drugs against this virus (with a binding energy around -5 and -7 kcal/mol). It is worth noting that this report is the first case of an inhibitory potential evaluation of phosphoramide compounds on Monkeypox.

Structural and Molecular Packing study of Three New Amidophosphoric Acid Esters and Assessment of Their Inhibiting Activity Against SARS-CoV-2 by Molecular Docking.

Three new compounds of amidophosphoric acid esters with a [OCH2C(CH3)2CH2O]P(O)[X] segment (where X=cyclopentylamido (1), 2-aminopyridinyl (2) and pyrrolidinyl (3)) were synthesized and studied using FT-IR and 31P/13C/1H NMR spectroscopies and single-crystal X-ray diffraction analysis. The compounds crystallize in the triclinic space groups P 1 ‾ for 1 and 3 and in the orthorhombic space group Pca21 for 2, where the asymmetric unit consists of three symmetrically-independent molecules for 1 and one molecule for 2 and 3. The intermolecular interactions and supramolecular assemblies are assessed by Hirshfeld surface analysis and enrichment ratios. The results reveal that the substituent effect plays an important role in directing the supramolecular structures. The presence of the aromatic substituent aminopyridine in 2 providing the C-H…π interactions leads to a larger variety in interactions including H…H, H…O/O…H, H…C/C…H and H…N/N…H contacts, whereas the packings of the compounds 1 and 3 bearing aliphatic substituents only include H…H and H…O/O…H contacts. The enrichment ratios affirm the importance of O…H/H…O contacts reflecting the hydrogen bond N-H…O interactions to be the enriched contacts. Compounds 1-3 were also investigated along with five similar reported structures with a [OCH2C(CH3)2CH2O]P(O) segment for their inhibitory behavior against SARS-CoV-2. The molecular docking results illustrate that the presence of the aromatic amido substituent versus the aliphatic type provides a more favorable condition for their biological activities.

Experimental and theoretical study of novel amino-functionalized P(V) coordination compounds suggested as inhibitor of MPro of SARS-COV-2 by molecular docking study.

Amino-functionalized P(V) derivatives providing both N- and O-donor modes have attracted interest owing to their potential to form interesting coordination assemblies with applications such as biological drugs. Novel coordination modes of two- and four-dentate tris (pyridin-2-yl)phosphoric triamide OP[NH-2Py]3 as ([Co(II){[O][NH-2Py]P(O)[Ph]}2(DMF)2], 1) and ([Cu(II)Cl{[NH-2Py]2P(O)[N-2Py]}].DMF, 2) have been synthesized and structurally studied. The metal center environment is distorted octahedral for 1 and distorted square pyramidal for 2. The crystal structure of a new complex of Cu(II) with a Cu[N]4[Cl]2 environment ([Cu(II)Cl2(Pyrazole)4], 3) is also investigated. An evaluation of the inhibitory effect against the coronavirus (Main Protease [MPro] of SARS-CoV-2) was carried out by a molecular docking study and illustrates that these compounds have a good interaction tendency with CoV-2, where 1 has the best binding affinity with the biological target comparable with other SARS-CoV-2 drugs. Moreover, theoretical QTAIM and natural bond orbital (NBO) calculations are used to evaluate the metal-oxygen/-nitrogen bonds suggesting that they are mainly electrostatic in nature with a slight covalent contribution. A molecular packing analysis using Hirshfeld surface (HS) analysis shows that N-H … O (in 1 and 2) and N-H … Cl (in 3) hydrogen bonds are the dominant interactions that contribute to the crystal packing cohesion. The semi-empirical PIXEL method indicates that the electrostatic and repulsion energy components in the structures of 1 and 2 and the dispersion and electrostatic components in that of 3 are the major contributors to the total lattice energy.

Coordination versus hydrogen bonds in the structures of different tris(pyridin-2-yl)phosphoric triamide derivatives.

The crystalline forms of tris(pyridin-2-yl)phosphoric triamide, OP[NH-2Py]3 were investigated using single crystal X-ray diffraction, both as a metal complex [Co{(O)P[NH-2Py]2[NH-2PyH]}2]Cl3, compound 1, and as the purely organic pseudopolymorphs, the pure/anhydrate OP[NH-2Py]3, 2, monohydrate 2OP[NH-2Py]3·H2O, 3 and solvate 2OP[NH-2Py]3·2DMF·H2O, 4, respectively. An improved model of the metal organic framework (MOF) structure of Cu(ii)O6 {[Cu(OCHO)3][(CH3)2NH2]} n , 5 is also reported. Compound 1 is the first example of a discrete chelate phosphoric triamide (PT) complex with an [N]3P(O)-based backbone which in the PT compound acts as a flexible tridentate ligand. The structures 1, 3 and 4 crystallize in the monoclinic space group P21/n, while the anhydrous form 2 crystallizes in the R3̄ trigonal space group. 5 which was obtained as a byproduct of the synthesis process of coordination compounds of OP[NH-2Py]3, crystallizes in the monoclinic space group I2/c. Hydrogen bonding pattern analysis for the different solid state forms of OP[NH-2Py]3 (2-4) shows a 2D sheet of the N-H⋯N linked molecules for 2, and a 1D chain and a ten-membered ring motif, both formed via the hydrogen bonds N-H⋯O, N-H⋯N and O-H⋯O, for 3 and 4, respectively. Of note is the unusual absence of the expected hydrogen bond interaction N-H⋯O[double bond, length as m-dash]P of PT compounds and also a lack of any significant π interactions in structure 2. The role of the solvent/hydrate and substituent (aminopyridine) in the formation of the expected hydrogen bond interactions in the studied solid state forms is also investigated. For these structures, crystal packing analysis using 3D Hirshfeld surface (HS), 2D fingerprint plot (FP) and enrichment ratio (E) calculations confirm a competition between the pyridinyl nitrogen and phosphoryl oxygen atoms as H-bond acceptors to construct the N-H⋯N or N-H⋯O contacts. Moreover, the significant differences between the anhydrous form of OP[NH-2Py]3, 2, and the monohydrate and solvate forms, 3 and 4, can be correlated to the pseudo-infinite (in 2) versus finite values (in 3 and 4) for the upper values of d e and d i on the related full FPs.

Syntheses and structures of four new mixed-amide phosphoric triamides.

Phosphoric triamides have extensive applications in biochemistry and are also used as O-donor ligands. Four new mixed-amide phosphoric triamide structures, namely rac-N-tert-butyl-N',N''-dicyclohexyl-N''-methylphosphoric triamide, C17H36N3OP, (I), rac-N,N'-dicyclohexyl-N'-methyl-N''-(p-tolyl)phosphoric triamide, C20H34N3OP, (II), N,N',N''-tricyclohexyl-N''-methylphosphoric triamide, C19H38N3OP, (III), and 2-[cyclohexyl(methyl)amino]-5,5-dimethyl-1,3,2λ(5)-diazaphosphinan-2-one, C12H26N3OP, (IV), have been synthesized and studied by X-ray diffraction and spectroscopic methods. Structures (I) and (II) are the first diffraction studies of acyclic racemic mixed-amide phosphoric triamides. The P-N bonds resulting from the different substituent -N(CH3)(C6H11), (C6H11)NH-, 4-CH3-C6H4NH-, (tert-C4H9)NH- and -NHCH2C(CH3)2CH2NH- groups are compared, along with the different molecular volumes and electron-donor strengths. In all four structures, the molecules form extended chains through N-H...O hydrogen bonds.

Three new phosphoric triamides with a [C(O)NH]P(O)[N(C)(C)]2 skeleton: a database analysis of C-N-C and P-N-C bond angles.

In N,N,N',N'-tetraethyl-N''-(4-fluorobenzoyl)phosphoric triamide, C15H25FN3O2P, (I), and N-(2,6-difluorobenzoyl)-N',N''-bis(4-methylpiperidin-1-yl)phosphoric triamide, C19H28F2N3O2P, (II), the C-N-C angle at each tertiary N atom is significantly smaller than the two P-N-C angles. For the other new structure, N,N'-dicyclohexyl-N''-(2-fluorobenzoyl)-N,N'-dimethylphosphoric triamide, C21H33FN3O2P, (III), one C-N-C angle [117.08 (12)°] has a greater value than the related P-N-C angle [115.59 (9)°] at the same N atom. Furthermore, for most of the analogous structures with a [C(=O)NH]P(=O)[N(C)(C)]2 skeleton deposited in the Cambridge Structural Database [CSD; Allen (2002). Acta Cryst. B58, 380-388], the C-N-C angle is significantly smaller than the two P-N-C angles; exceptions were found for four structures with the N-methylcyclohexylamide substituent, similar to (III), one structure with the seven-membered cyclic amide azepan-1-yl substituent and one structure with an N-methylbenzylamide substituent. The asymmetric units of (I), (II) and (III) contain one molecule, and in the crystal structures, adjacent molecules are linked via pairs of N-H···O=P hydrogen bonds to form dimers.

Hirshfeld surface analysis of the 1,1'-(ethane-1,2-diyl)dipyridinium dication in two new salts: perchlorate and peroxodisulfate.

In the title salts, C12H14N2(2+)·2ClO4(-), (I), and C12H14N2(2+)·S2O8(2-), (II), the dication is organized around an inversion centre located at the centre of the -CH2CH2- bridge and the two pyridine segments are anti with respect to one another. The peroxodisulfate anion in (II) also exhibits inversion symmetry. Hirshfeld surface analysis shows closely similar Hirshfeld surface shapes for the dications in the two salts, reflecting similar intermolecular contacts and similar conformations. The two-dimensional fingerprint plots (FPs) are quite asymmetric, due to the presence of more than one component (cation and anion). The most striking of the complementary features for each of the FPs of the dications is the broad green spike in the region d(e) > d(i), without the presence of a corresponding spike in the region d(e) < d(i), reflecting the absence of O···H contacts. Moreover, H···O interactions (51% in the dications of both salts) outnumber other contacts in both crystal structures.

Hirshfeld surface analysis of new phosphoramidates.

Hirshfeld surfaces and two-dimensional fingerprint plots are used to visualize and analyze intermolecular interactions in six new phosphoramidate structures, [2,6-F2-C6H3C(O)NH]P(O)[X]2 {X = N(C2H5)2 (1), [X]2 = NHCH2C(CH3)2CH2NH and with one CH3OH solvated molecule (2)}, [C6H5O]2P(O)Y [Y = NC4H8O (3), NHC6H4(3-Br) (4)] and [Z]2P(O)OP(O)[Z]2 [Z = N(CH3)(CH2C6H5) (5), NHC6H4(4-CH3) (6)]. Study of the short intermolecular contacts in structures (1)-(6) by Hirshfeld surfaces demonstrate that the O atom of P=O is a better H-atom acceptor than the O atom of C=O for (1) and (2), and also relative to the O atom of the C6H5O group for (3) and (4), and relative to the bridge O atom of the P(O)OP(O) segment for (5) and (6). The results confirm that the crystal packing is related to the kind of substituent linked to the P atom. Compounds (1), (2), (4) and (6), with characteristic N-H···O hydrogen bonds, show a pair of intense spikes (including the intermolecular H···O contacts) in the fingerprint plots, summarizing the major features of each structure in the related two-dimensional plot. For (3) and (5), without any N-H unit, the two short spikes are observed for (3) but are absent for (5). The upper d(e) and d(i) values (distances to the Hirshfeld surfaces for the nearest atoms outside and inside) in the fingerprint plots are more compact in (3) than in (4), and in (5) than in (6), reflecting the more efficient packing in (3) and (5). The tertiary N atoms of (3) and (5) do not take part in any intermolecular contacts involving H atoms. Moreover, structures (3)-(6) show greater contribution from C···H contacts relative to O···H contacts. Finally, Hirshfeld surfaces and fingerprint plots are employed for a comparison of the two independent molecules in the asymmetric unit of (1) and also, for a comparison of (6), in the orthorhombic crystal system, with the previously reported monoclinic polymorph (Pourayoubi, Fadaei et al., 2012).

A novel amido-pyrophosphate Mn(II) chelate complex with the synthetic ligand O{P(O)[NHC(CH3)3]2}2 (L): [Mn(L)2{OC(H)N(CH3)2}2]Cl2·2H2O.

The title complex, trans-bis(dimethylformamide-κO)bis{N,N'-N'',N'''-tetra-tert-butyl[oxybis(phosphonic diamide-κO)]}manganese(II) dichloride dihydrate, [Mn(C16H40N4O3P2)2(C3H7NO)2]Cl2·2H2O, is the first example of a bis-chelate amido-pyrophosphate (pyrophosphoramide) complex containing an O[P(O)(NH)2]2 fragment. Its asymmetric unit contains half of the complex dication, one chloride anion and one water molecule. The Mn(II) atom, located on an inversion centre, is octahedrally coordinated, with a slight elongation towards the monodentate dimethylformamide ligand. Structural features of the title complex, such as the P=O bond lengths and the planarity of the chelate ring, are compared with those of previously reported complexes with six-membered chelates involving the fragments C(O)NHP(O), (X)NP(O) [X = C(O), C(S), S(O)2 and P(O)] and O[P(O)(N)2]2. This analysis shows that the six-membered chelate rings are less puckered in pyrophosphoramide complexes containing a P(O)OP(O) skeleton, such as the title compound. The extended structure of the title complex involves a linear aggregate mediated by N-H...O and N-H...Cl hydrogen bonds, in which the chloride anion is an acceptor in two additional O-H...Cl hydrogen bonds.

A second monoclinic polymorph of N-[bis-(morpholin-4-yl)phosphino-yl]-4-fluoro-benzamide with the P2(1)/n space group.

A second monoclinic polymorph of the title mol-ecule, C(15)H(21)FN(3)O(4)P, is reported in the space group P2(1)/n and compared to the previously reported C2/c space group [Gholivand et al. (2006 ▶). Polyhedron, 25, 711-721]. The asymmetric unit of the title compound consists of two independent mol-ecules. The P atoms adopt a distorted tetra-hedral environment. In the C(O)NHP(O) fragment, the P=O and the N-H groups are in a syn conformation with respect to each other and in the crystal, inter-molecular N-H⋯O=P hydrogen bonds form dimeric aggregates.

Two new XP(O)[NHC(CH3)3]2 phosphoramidates, with X = (CH3)2N and [(CH3)3CNH]2P(O)(O).

In N,N'-di-tert-butyl-N'',N''-dimethylphosphoric triamide, C(10)H(26)N(3)OP, (I), and N,N',N'',N'''-tetra-tert-butyl[oxybis(phosphonic diamide), [corrected] C(16)H(40)N(4)O(3)P(2), (II), the extended structures are mediated by P(O)...(H-N)(2) interactions. The asymmetric unit of (I) consists of six independent molecules which aggregate through P(O)...(H-N)(2) hydrogen bonds, giving R(2)(1)(6) loops and forming two independent chains parallel to the a axis. Of the 12 independent tert-butyl groups, five are disordered over two different positions with occupancies ranging from 1/6 to 5/6. In the structure of (II), the asymmetric unit contains one molecule. P(O)...(H-N)(2) hydrogen bonds give S(6) and R(2)(2)(8) rings, and the molecules form extended chains parallel to the c axis. The structures of (I) and (II), along with similar structures having (N)P(O)(NH)(2) and (NH)(2)P(O)(O)P(O)(NH)(2) skeletons extracted from the Cambridge Structural Database, are used to compare hydrogen-bond patterns in these families of phosphoramidates. The strengths of P(O)[...H-N](x) (x = 1, 2 or 3) hydrogen bonds are also analysed, using these compounds and previously reported structures with (N)(2)P(O)(NH) and P(O)(NH)(3) fragments.

N-(4-Fluoro-benzo-yl)-N',N''-diisopropyl-phospho-ric triamide.

The asymmetric unit of the title phospho-ric triamide, C13H21FN3O2P, consists of two independent mol-ecules. In each mol-ecule, the P=O group and the N-H unit belonging to the C(O)NHP(O) fragment are in a syn conformation with respect to each other. An intra-molecular N-H⋯O hydrogen bond occurs in each mol-ecule. The P atom adopts a distorted tetra-hedral environment. The methyl groups of an isopropyl fragment are disordered over two sets of sites with refined occupancies of 0.458 (5) and 0.542 (5). In the crystal, mol-ecules are linked through N-H⋯O(=P) and N-H⋯O(=C) hydrogen bonds into chains along [001].

N,N,N',N'-Tetra-benzyl-N''-(2,6-difluoro-benzo-yl)phospho-ric triamide.

In the C(O)NHP(O) fragment of the title compound, C(35)H(32)F(2)N(3)O(2)P, the P-N bond is longer and the O-P-N angle is contracted compared with the other two P-N bonds and O-P-N angles. The P atom adopts a distorted tetra-hedral environment and the phosphoryl and carbonyl groups are anti with respect to each other. The two tertiary N atoms of the dibenzyl-amido groups show sp(2) character with a slight deviation from planarity. In the crystal, pairs of N-H⋯O(P) hydrogen bonds form inversion dimers.

O-Phenyl (tert-butyl-amido)(p-tolyl-amido)-phosphinate.

In the title mol-ecule, C(17)H(23)N(2)O(2)P, the P atom has a distorted tetra-hedral environment. The P-N bond to the tolyl-amido fragment is 1.642 (4) Šwhile that to the butyl-amido fragment is 1.629 (3) Å. The dihedral angle between the two benzene rings is 82.3 (2)°. In the crystal, adjacent mol-ecules are linked via weak N-H⋯(O)P and N-H⋯N hydrogen-bonding inter-actions into an extended chain parallel to the b axis. The three methyl groups of the tert-butyl-amido substituent are disordered over two sets of sites with equal occupancies. The crystal studied was found to be a non-merohedral twin with the minor twin component = 23.1 (1)%.

N,N,N',N'-Tetra-ethyl-N''-(2-fluoro-benzo-yl)phospho-ric triamide.

In the title compound, C(15)H(25)FN(3)O(2)P, the phosphoryl group is in an anti and syn orientation to the C=O and N-H groups, respectively. The P atom is in a distorted tetra-hedral environment. One of the ethyl groups is disordered over two sets of sites with refined occupancies of 0.755 (6) and 0.245 (6). In addition, the F atom was refined as disordered with occupancies fixed at 0.9 and 0.1. This disorder corresponds to a rotation of approximately 180° of the fluoro-benzene ring about its connecting C-C bond. In the crystal, pairs of inter-molecular N-H⋯O(=P) hydrogen bonds form centrosymmetric dimers.

N-(2,6-Difluoro-benzo-yl)-P,P-bis-(pyrrolidin-1-yl)phosphinic amide.

The phosphoryl and carbonyl groups in the title compound, C(15)H(20)F(2)N(3)O(2)P, are anti with respect to each other (but the P- and C-groups are separated by another atom) and the P atom is in a tetra-hedral coordination environment. Two C atoms in one of the pyrrolidinyl fragments are disordered over two sets of sites with occupancies of 0.746 (8) and 0.254 (8). The environments of the pyrrolidinyl N atoms show a slight deviation from planarity and none of the three N atoms is involved in any hydrogen bond as an acceptor. In the crystal, pairs of inter-molecular N-H⋯O hydrogen bonds form inversion dimers.

Cyclo-hex-yl(meth-yl)ammonium {bis-[cyclo-hex-yl(meth-yl)amino]-phosphor-yl}(4-methyl-phenyl-sulfon-yl)aza-nide.

In the anion of the title salt, C(7)H(16)N(+)·C(21)H(35)N(3)O(3)PS(-), the P and S atoms are both in distorted tetra-hedral environments and the angles at the tertiary N atoms confirm their sp(2) character. The two S=O groups are in syn and gauche conformations with respect to the phosphoryl group. In the crystal, N-H⋯O(=S) and N-H⋯O(=P) hydrogen bonds involving two anions and two cations form a centrosymmetric four-component cluster.

Different cyclic motifs in phosphoric triamides containing a C(O)NHP(O)(NH)2 skeleton and an R(2)(2)(10) graph set in three new compounds: a database analysis of hydrogen-bond strengths based on motifs.

In the crystal networks of N,N'-bis(2-chlorobenzyl)-N''-(2,6-difluorobenzoyl)phosphoric triamide, C(21)H(18)Cl(2)F(2)N(3)O(2)P, (I), N-(2,6-difluorobenzoyl)-N',N''-bis(4-methoxybenzyl)phosphoric triamide, C(23)H(24)F(2)N(3)O(4)P, (II), and N-(2-chloro-2,2-difluoroacetyl)-N',N''-bis(4-methylphenyl)phosphoric triamide, C(16)H(17)ClF(2)N(3)O(2)P, (III), C=O···H-N(C(O)NHP(O)) and P=O···H-N(amide) hydrogen bonds are responsible for the aggregation of the molecules. This is the opposite result from that commonly observed for carbacylamidophosphates, which show a tendency for the phosphoryl group, rather than the carbonyl counterpart, to form hydrogen bonds with the NH group of the C(O)NHP(O) skeleton. This hydrogen-bond pattern leads to cyclic R(2)(2)(10) motifs in (I)-(III), different from those found for all previously reported compounds of the general formula RC(O)NHP(O)[NR(1)R(2)](2) with the syn orientation of P=O versus NH [R(2)(2)(8)], and also from those commonly observed for RC(O)NHP(O)[NHR(1)](2) [a sequence of alternate R(2)(2)(8) and R(2)(2)(12) motifs]. In these cases, the R(2)(2)(8) and R(2)(2)(12) graph sets are formed through similar kinds of hydrogen bond, i.e. a pair of P=O···H-N(C(O)NHP(O)) hydrogen bonds for the former and two C=O···H-N(amide) hydrogen bonds for the latter. This article also reviews 102 similar structures deposited in the Cambridge Structural Database and with the International Union of Crystallography, with the aim of comparing hydrogen-bond strengths in the above-mentioned cyclic motifs. This analysis shows that the strongest N-H···O hydrogen bonds exist in the R(2)(2)(8) rings of some molecules. The phosphoryl and carbonyl groups in each of compounds (I)-(III) are anti with respect to each other and the P atoms are in a tetrahedral coordination environment. In the crystal structures, adjacent molecules are linked via the above-mentioned hydrogen bonds in a linear arrangement, parallel to [010] for (I) and (III) and parallel to [100] for (II). Formation of the N(C(O)NHP(O))-H···O=C instead of the N(C(O)NHP(O))-H···O=P hydrogen bond is reflected in the higher N(C(O)NHP(O))-H vibrational frequencies for these molecules compared with previously reported analogous compounds.

N-(2-Fluoro-benzo-yl)-N',N''-bis-(4-methyl-phen-yl)phospho-ric triamide.

The P atom in the title compound, C(21)H(21)FN(3)O(2)P, is in a tetra-hedral coordination environment and the environment of each N atom is essentially planar (sums of angles = 359.7, 359.9 and 358.4°). The phosphoryl and carbonyl groups adopt anti orientations with respect to each other. In the crystal, adjacent mol-ecules are linked via N-H⋯O=P and two N-H⋯O=C hydrogen bonds into an extended chain parallel to the a axis.

N,N'-Dicyclo-hexyl-N''-(2,6-difluoro-benzo-yl)-N,N'-dimethyl-phospho-ric triamide.

In the title mol-ecule, C(21)H(32)F(2)N(3)O(2)P, the P=O and N-H groups are syn with respect to each other, and the P atom is bonded in a distorted tetra-hedral environment. The phosphoryl group adopts an anti orientation with respect to the carbonyl group. The angles at the tertiary N atoms (with bond-angle sums of 358.4 and 357.0°) confirm their sp(2) character. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds generate R(2) (2)(8) loops.