Acta Crystallographica Section E
`Structure Reports
`Online
`
`ISSN 1600-5368
`
`Tris(5-amino-1H-1,2,4-triazol-4-ium)
`dihydrogenphosphate hydrogen-
`phosphate trihydrate
`
`Mohamed Lahbib Mrad,a Matthias Zeller,b Kristen J.
`Hernandez,b Mohamed Rzaiguia and Cherif Ben Nasra*
`
`aLaboratoire de Chimie des Mate´riaux, Faculte´ des sciences de Bizerte, 7021
`Zarzouna, Tunisia, and bYoungstown State University, Department of Chemistry,
`One University Plaza, Youngstown, Ohio 44555-3663, USA
`Correspondence e-mail: cherif_bennasr@yahoo.fr
`
`Received 7 October 2012; accepted 26 October 2012
`
`Key indicators: single-crystal X-ray study; T = 100 K; mean (N–C) = 0.002 A˚;
`R factor = 0.023; wR factor = 0.059; data-to-parameter ratio = 19.3.
`
`+ -
`In the crystal structure of the title molecular salt, 3C2H5N4
`2 H2PO4HPO4 3H2O, the phosphate-based framework is
`
`
`
`built upon layers parallel to (010) made up from the H2PO4
`2
`anions and water molecules, which are inter-
`and HPO4
`connected through O—H O hydrogen bonds. The organic
`cations are located between the phosphate–water layers and
`are connected to them via N—H O hydrogen bonds. The
`bond-length features are consistent with an imino resonance
`form for the exocyclic amino group, as is commonly found for
`a C—N single bond involving sp2-hybridized C and N atoms.
`
`Related literature
`
`see:
`For applications of organic phosphate complexes,
`Bringley & Rajeswaran (2006); Dai et al. (2002); Masse et al.
`(1993). For graph-set motifs and theory, see: Bernstein et al.
`(1995). For reference structural data, see: Kaabi et al. (2004);
`Shanmuga Sundara Raj et al. (2000). For P—OH bond lengths,
`see: Chtioui & Jouini (2005).
`
`Experimental
`
`Crystal data
`+ HO4P2 H2O4P3C2H5N4
`
`Mr = 502.31
`Monoclinic, Pc
`a = 10.4793 (13) A˚
`b = 8.7655 (11) A˚
`c = 11.4536 (14) A˚
`

= 107.489 (2)
`
` 3H2O
`
`V = 1003.5 (2) A˚ 3
`Z = 2
`Mo K radiation
`1
` = 0.30 mm
`T = 100 K
`0.60  0.35  0.18 mm
`
`organic compounds
`
`Data collection
`
`Bruker SMART APEX CCD
`diffractometer
`Absorption correction: multi-scan
`(SADABS; Bruker, 2011)
`Tmin = 0.693, Tmax = 0.746
`
`Refinement
`R[F 2 > 2(F 2)] = 0.023
`wR(F 2) = 0.059
`S = 1.04
`6229 reflections
`322 parameters
`32 restraints
`
`D—H
`
`Table 1
`Hydrogen-bond geometry (A˚ , ).
`D—H A
`N1A—H1A1 O3B
`0.85 (1)
`N1A—H1A2 N3Ai
`0.85 (1)
`N2A—H2A O4B
`0.88
`N4A—H4A O4Bi
`0.88
`N1B—H1B1 O2
`0.86 (1)
`N1B—H1B2 N3Bi
`0.82 (1)
`N2B—H2B1 O3ii
`0.88
`N4B—H4B O1Aiii
`0.88
`N1C—H1C1 N3C i
`0.83 (1)
`N1C—H1C2 O3A
`0.86 (1)
`N2C—H2C O4A
`0.88
`N4C—H4C O4Ai
`0.88
`O2A—H2AB O3Biv
`0.76
`O1B—H1B O3A
`0.77
`O2B—H2BA O1iv
`0.83
`O1—H1D O2
`0.84 (1)
`O1—H1E O3B
`0.80 (1)
`O2—H2D O1Av
`0.82 (1)
`O2—H2E O3Aiii
`0.81 (1)
`O3—H3D O2B
`0.79 (1)
`O3—H3E O1Aiii
`0.80 (1)
`(i) x;y; z þ 1
`Symmetry codes:
`2;
`x; y þ 1; z 1
`2; (v) x þ 1; y; z þ 1.
`
`13833 measured reflections
`6229 independent reflections
`6132 reflections with I > 2(I)
`Rint = 0.016
`
`H atoms treated by a mixture of
`independent and constrained
`refinement
` max = 0.33 e A˚ 3
` min = 0.19 e A˚ 3
`Absolute structure: Flack (1983),
`2950 Friedel pairs
`Flack parameter: 0.02 (4)
`
`H A
`
`D A
`
`D—H A
`
`2.31 (1)
`2.19 (1)
`1.77
`1.76
`1.96 (1)
`2.28 (1)
`1.84
`1.87
`2.18 (1)
`2.24 (1)
`1.78
`1.79
`1.95
`1.80
`1.73
`1.93 (1)
`1.91 (1)
`1.90 (1)
`1.95 (1)
`2.14 (2)
`1.92 (1)
`(ii) x; y 1; z;
`
`3.1356 (13)
`162 (2)
`3.0305 (15)
`170 (2)
`2.6130 (13)
`161
`2.6314 (13)
`171
`2.8214 (13)
`178 (2)
`3.0639 (15)
`160 (2)
`2.6824 (13)
`159
`2.7376 (12)
`167
`3.0028 (14)
`172 (2)
`3.0589 (13)
`160 (2)
`2.6278 (12)
`161
`2.6645 (12)
`170
`2.6593 (11)
`155
`2.5495 (12)
`161
`2.5552 (12)
`176
`2.7439 (12)
`166 (2)
`2.6968 (12)
`168 (2)
`2.7024 (11)
`168 (2)
`2.7566 (12)
`178 (2)
`2.8515 (12)
`149 (2)
`2.7085 (11)
`176 (2)
`(iii) x þ 1; y þ 1; z þ 1
`2;
`
`(iv)
`
`Data collection: APEX2 (Bruker, 2011); cell refinement: SAINT
`(Bruker, 2011); data reduction: SAINT; program(s) used to solve
`structure: SHELXTL (Sheldrick, 2008); program(s) used to refine
`structure: SHELXLE (Hu¨ bschle et al., 2011); molecular graphics:
`SHELXTL (Sheldrick, 2008); software used to prepare material for
`publication: SHELXTL and publCIF (Westrip, 2010).
`
`We would like to acknowledge the support provided by the
`Secretary of State for Scientific Research and Technology of
`Tunisia. The diffractometer was funded by NSF grant 0087210,
`by Ohio Board of Regents grant CAP-491, and by YSU.
`
`Supplementary data and figures for this paper are available from the
`IUCr electronic archives (Reference: RU2044).
`
`References
`
`Bernstein, J., Davids, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem.
`Int. Ed. Engl. 34, 1555–1573.
`Bringley, J. F. & Rajeswaran, M. (2006). Acta Cryst. E62, m1304–m1305.
`Bruker (2011). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison,
`Wsiconsin, USA.
`Chtioui, A. & Jouini, A. (2005). Mater. Res. Bull. 41, 569–575.
`
`Acta Cryst. (2012). E68, o3257–o3258
`
`doi:10.1107/S1600536812044492
`
`Mrad et al. o3257
`
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`organic compounds
`
`Dai, J.-C., Wu, X.-T., Fu, Z.-Y., Cui, C.-P., Wu, S.-M., Du, W.-X., Wu, L.-M.,
`Zhang, H.-H. & Sun, Q.-Q. (2002). Inorg. Chem. 41, 1391–1396.
`Flack, H. D. (1983). Acta Cryst. A39, 876–881.
`Hu¨ bschle, C. B., Sheldrick, G. M. & Dittrich, B. (2011). J. Appl. Cryst. 44, 1281–
`1284.
`Kaabi, K., Ben Nasr, C. & Lefebvre, F. (2004). Mater. Res. Bull. 39, 205–215.
`
`Masse, R., Bagieu-Beucher, M., Pecaut, J., Levy, J. P. & Zyss, J. (1993). J.
`Nonlinear Opt. 5, 413–423.
`Shanmuga Sundara Raj, S., Fun, H.-K., Zhao, P.-S., Jian, F.-F., Lu, L.-D., Yang,
`X.-J. & Wang, X. (2000). Acta Cryst. C56, 742–743.
`Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.
`Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925.
`
`o3258 Mrad et al.
`
`
`
` 3C2H5N4+ HO4P2 H2O4P 3H2O
`
`
`
`Acta Cryst. (2012). E68, o3257–o3258
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`supporting information
`
`supporting information
`
`Acta Cryst. (2012). E68, o3257–o3258 [doi:10.1107/S1600536812044492]
`
`Tris(5-amino-1H-1,2,4-triazol-4-ium) dihydrogenphosphate hydrogenphosphate
`trihydrate
`
`Mohamed Lahbib Mrad, Matthias Zeller, Kristen J. Hernandez, Mohamed Rzaigui and Cherif
`
`Ben Nasr
`
`S1. Comment
`
`Inorganic–organic hybrid compounds provide a class of materials with interesting technological applications (Bringley &
`Rajeswaran, 2006; Dai et al., 2002). Among these materials, compounds with noncentrosymmetric crystallographic
`structures are interesting for their applications in quadratic non-linear optical materials research (Masse et al., 1993).
`Their abilities to combine the rigidity and high cohesion of inorganic host matrices with the enhanced polarizability of
`organic guest chromophores within one molecular scale assists in better performance of optical signal-processing devices.
`The use of organic-inorganic polar crystalline materials for quadratic nonlinear optical applications is supported by two
`observations:
`(i) the organic molecules, especially if they contain a delocalized π-system with asymmetric substitution by electron
`donor-acceptor groups, are highly polarizable entities idealy suited for NLO applications. Being organic materials, the
`nature of the substituents can be tailored so as to not affect optical transparency;
`(ii) the ionic inorganic host matrices are able to increase the packing cohesion, can induce noncentrosymmetry, and also
`shift the transparency of crystal towards blue wavelengths.
`Within a systematic investigation of new materials resulting from the association of organic chromophores with
`inorganic species, we report here the synthesis and the characterization of a new hybrid phosphate-amine material,
`(C2H5N4)3(HPO4)(H2PO4).3H2O, which includes the 3-amino-1H-1,2,4-triazolium cations, a chromophore which could be
`efficient in the blue-U.V. wavelength region. The title compound could exhibit a richness of interesting physical
`properties such as ferroelectricity and nonlinear optic phenomena like second harmonic generation. It crystallizes in a
`non-centrosymmetric setting in the space group Pc. The structure of this organic-inorganic hybrid material consists of one
`dihydrogenmonophosphate anion, one monohydrogenmonophosphate dianion, three crystallographically independent 3-
`amino-1H-1,2,4-triazolium cations and three water molecules (Fig. 1). The atomic arrangement is a typical layered
`organization as it is very often encountered in this kind of inorganic-organic hybrid compounds (Kaabi et al., 2004). The
`2- groups and one of the water molecules (that of O3) to form H2PO4- anions are hydrogen bonded with the HPO4
`
`
`corrugated chains running parallel to the a-axis at (0, 0, 0) and (0, 0, 1/2). These chains are interconnected, via O(water)
`—H···O and O—H···O(water) hydrogen bonds, with the two remaining water molecules H2O(1) and H2O(2), associated
`through O1—H···O2 hydrogen bonds, on one hand, and with the HPO4
`2- anions of the adjacent chain, trough O—H···O
`hydrogen bonds, on the other hand. These hydrogen bonds link the different inorganic units into infinite planar layers
`parallel to the (0 1 0) plane (Fig. 2) crossing the unit cell at y = (2n +1)/2 (Fig. 3). Within the layers, various graph-set
`5(10) and R44(12) loops. The 3-amino-1H-1,2,4-triazolium
`
`motifs (Bernstein et al., 1995) are apparent, including R5
`cations are interconnected via weak N—H···N hydrogen bonds, with D—H···A distances between 3.003 (1) and 3.064 (1)
`
`Acta Cryst. (2012). E68, o3257–o3258
`
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`Å, to form organic chains spreading along the c-axis at x ~ (n + 1)/3 (Fig. 4). The chains are build from the three
`crystallographically independent organic cations, labelled A, B and C, in such a way that each N—H···N connected chain
`incorporates only one type of cation: Molecules of type A are located at x ~1/3, chains at x ~ 0 consist of molecules of
`type B, and the chains at x~2/3 are made up of molecules C. Alternating molecules in each of these chains are created by
`the c-glide plane. In two of the chains, that of molecules A and C, alternating molecules are roughly coplanar. In the third,
`molecules are twisted against each other by an angle of 34.37°. The chains are roughly parallel to each other and weakly
`π-stacked, with interplanar distances between the mean planes of chains between 3.21 Å (between A and C), and up to
`3.52 Å (for A and B). Despite of the quite close interplanar distances, π-π stacking interactions are limited due to
`molecule offsets in parallel layers, and the non-coplanarity of neighboring molecules in the chains of molecules B. The
`organic chains are anchored to the inorganic layers through N—H···O hydrogen bonds whose geometrical characteristics
`are given in Table 2. The projection of the whole arrangement along the a-axis (Fig. 4) shows how the organic chains
`alternate as to fill the space separating parallel inorganic layers. In this structure, three 3-amino-1H-1,2,4-triazolium
`cationic groups compensate the negative charges of the dihydrogenmonophosphate and the mono-
`hydrogenmonophosphate anions, leading to charge neutrality for the structure as a whole.
`The sum of the angles around the N1A, N1B and N1C nitrogen atoms are 360° and the C—N bond distances of the NH2
`groups are 1.332 (1) Å for N1A—C1A, 1.327 (1) Å for N1B—C1B and 1.330 (1) Å for N1C—C1C, which are short for
`C—N single bonds, but still not quite as contracted as one would expect for a fully established C=N double bond. These
`bond length features are consistent with an imino resonance form as it is commonly found for a C—N single bond
`involving sp2 hybridized C and N atoms (Shanmuga Sundara Raj et al., 2000). In agreement with this, the amino groups
`are not pyramidal but the electron densities of the hydrogen atoms of the amino groups were found to be in plane with the
`
`- anions shows two kinds 3-amino-1H-1,2,4-triazolium skeleton. The detailed geometry of the HP(1 A)O42- and H2P(1B)O4
`
`of P—O distances. The shortest ones, 1.5243 (8), 1.5294 (8) and 1.5364 Å for the first anion (labelled A) and 1.5132 (8)
`and 1.5163 (8) Å for the second one (labelled B), correspond to the phosphorous atom doubly bonded to the oxygen
`atom, while the largest ones 1.5845 (8) Å and (1.5612 (8), 1.5741 (8) Å, respectively, can be attributed to the P—OH
`bond length. This is in agreement with the literature data (Chtioui & Jouini, 2005). Refining the structure in the
`asymmetric space group gives a value of -0.02 (4) for the Flack parameter (Flack, 1983), confirming the absolute
`structure and absence of twinning.
`
`S2. Experimental
`
`Crystals of the title compound were prepared at room temperature by slow addition of a solution of orthophosphoric acid
`(8 mmol in 30 ml of water) to an alcoholic solution of 3-amino-1H-1,2,4-triazole (12 mmol in 30 ml of ethanol). The acid
`was added until the alcoholic solution became turbid. After filtration, the solution was allowed to slowly evaporate at
`room temperature over several days leading to formation of transparent prismatic crystals with suitable dimensions for
`single-crystal structural analysis (1.2 mg, 2.4 mmol, yield 60%). The crystals are stable for months under normal
`conditions of temperature and humidity.
`
`S3. Refinement
`
`H atoms were placed in calculated positions with the exception of water and NH2 H atoms, which were located in
`difference density maps and were refined. C—H distances were set to 0.95 Å, Nring—H distances to 0.88 Å. H atoms of P-
`bound hydroxy groups were placed geometrically with fixed P—O—H angles, but with variable torional angles and O—
`H distances to best fit the experimental electron density (AFIX 148 in SHELXTL, Sheldrick 2008). All H2O O—H
`distances were restrained to be similar within a standard deviation of 0.02 Å. All amino N—H distances were also
`
`Acta Cryst. (2012). E68, o3257–o3258
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`restrained to be similar within the same standard deviation. Uiso values of H atoms were set to 1.2 or 1.5 times Ueq of their
`respective carrier atom for amino and O-bound H atoms respectively.
`
`supporting information
`
`Figure 1
`A view of the title compound, showing 40% probability displacement ellipsoids and arbitrary spheres for the H atoms.
`
`Acta Cryst. (2012). E68, o3257–o3258
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`Figure 2
`Projection along the b-axis of the inorganic layers in the structure of the title compound. PO4 is given in the tetrahedral
`representation. Hydrogen bonds are shown as broken lines.
`
`Figure 3
`The packing diagram of the compound viewed down the a-axis. PO4 is given in the tetrahedral representation. Hydrogen
`bonds are shown as broken lines.
`
`Acta Cryst. (2012). E68, o3257–o3258
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`Figure 4
`Projection along the b axis of the organic chains in the structure of the title compound. Hydrogen bonds are shown as
`broken lines. Numbers are interplanar spacings between layers of organic molecules of type A, B and C.
`
`Tris(5-amino-1H-1,2,4-triazol-4-ium) dihydrogenphosphate hydrogenphosphate trihydrate
`
`Crystal data
`
`3C2H5N4+·HO4P2−·H2O4P−·3H2O
`Mr = 502.31
`Monoclinic, Pc
`Hall symbol: P -2yc
`a = 10.4793 (13) Å
`b = 8.7655 (11) Å
`c = 11.4536 (14) Å
`β = 107.489 (2)°
`V = 1003.5 (2) Å3
`Z = 2
`
`Data collection
`Bruker SMART APEX CCD
`diffractometer
`Radiation source: fine-focus sealed tube
`Graphite monochromator
`ω scans
`Absorption correction: multi-scan
`(SADABS; Bruker, 2011)
`Tmin = 0.693, Tmax = 0.746
`
`F(000) = 524
`Dx = 1.662 Mg m−3
`Mo Kα radiation, λ = 0.71073 Å
`Cell parameters from 5573 reflections
`θ = 3.0–31.8°
`µ = 0.30 mm−1
`T = 100 K
`Block, colourless
`0.60 × 0.35 × 0.18 mm
`
`13833 measured reflections
`6229 independent reflections
`6132 reflections with I > 2σ(I)
`Rint = 0.016
`θmax = 32.0°, θmin = 2.3°
`h = −14→15
`k = −12→13
`l = −16→16
`
`Acta Cryst. (2012). E68, o3257–o3258
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`Refinement
`Refinement on F2
`Least-squares matrix: full
`R[F2 > 2σ(F2)] = 0.023
`wR(F2) = 0.059
`S = 1.04
`6229 reflections
`322 parameters
`32 restraints
`Primary atom site location: structure-invariant
`direct methods
`Secondary atom site location: difference Fourier
`map
`
`Hydrogen site location: inferred from
`neighbouring sites
`H atoms treated by a mixture of independent
`and constrained refinement
`w = 1/[σ2(Fo2) + (0.0385P)2 + 0.0562P]
`
`
`where P = (Fo2 + 2Fc
`2)/3
`(Δ/σ)max < 0.001
`Δρmax = 0.33 e Å−3
`Δρmin = −0.19 e Å−3
`Absolute structure: Flack (1983), 2950 Friedel
`pairs
`Absolute structure parameter: −0.02 (4)
`
`Special details
`Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full
`covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and
`torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry.
`An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.
`Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2,
`conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used
`only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2
`are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.
`
`Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
`
`N1A
`H1A1
`H1A2
`N2A
`H2A
`N3A
`N4A
`H4A
`C1A
`C2A
`H2AA
`N1B
`H1B1
`H1B2
`N2B
`H2B1
`N3B
`N4B
`H4B
`C1B
`C2B
`H2B2
`N1C
`
`x
`
`0.62032 (11)
`0.6049 (17)
`0.6042 (17)
`0.60906 (10)
`0.6141
`0.59896 (10)
`0.60216 (9)
`0.6017
`0.61011 (10)
`0.59494 (11)
`0.5879
`0.95278 (11)
`0.9835 (17)
`0.9369 (18)
`0.92010 (10)
`0.8958
`0.93026 (11)
`0.98316 (9)
`1.0082
`0.95240 (10)
`0.96750 (11)
`0.9821
`0.28072 (10)
`
`y
`
`0.15272 (11)
`0.2392 (16)
`0.1391 (19)
`0.04376 (11)
`0.1293
`−0.09961 (11)
`−0.11435 (11)
`−0.1543
`0.03524 (12)
`−0.19168 (13)
`−0.2995
`0.16763 (12)
`0.2502 (16)
`0.0936 (17)
`0.02876 (11)
`−0.0591
`0.05748 (11)
`0.26338 (10)
`0.3574
`0.15303 (12)
`0.19962 (13)
`0.2531
`0.15370 (11)
`
`z
`
`0.77449 (9)
`0.7386 (16)
`0.8421 (13)
`0.58172 (9)
`0.5432
`0.52940 (9)
`0.72352 (9)
`0.7939
`0.69840 (10)
`0.61746 (10)
`0.6093
`0.67577 (9)
`0.7144 (15)
`0.7129 (16)
`0.48939 (9)
`0.5132
`0.37327 (10)
`0.49075 (8)
`0.5133
`0.56033 (10)
`0.37803 (10)
`0.3110
`0.42295 (9)
`
`Uiso*/Ueq
`0.01772 (18)
`0.021*
`0.021*
`0.01488 (17)
`0.018*
`0.01524 (17)
`0.01336 (16)
`0.016*
`0.01299 (18)
`0.01451 (18)
`0.017*
`0.01933 (19)
`0.023*
`0.023*
`0.01598 (17)
`0.019*
`0.01706 (18)
`0.01343 (16)
`0.016*
`0.01362 (18)
`0.01543 (19)
`0.019*
`0.01621 (17)
`
`Acta Cryst. (2012). E68, o3257–o3258
`
`sup-6
`
`Merck Exhibit 2215, Page 8
`Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.
`IPR2020-00040
`
`

`

`supporting information
`
`H1C1
`H1C2
`N2C
`H2C
`N3C
`N4C
`H4C
`C1C
`C2C
`H2CA
`P1A
`O1A
`O2A
`H2AB
`O3A
`O4A
`P1B
`O1B
`H1B
`O2B
`H2BA
`O3B
`O4B
`O1
`H1D
`H1E
`O2
`H2D
`H2E
`O3
`H3D
`H3E
`
`0.2900 (16)
`0.2796 (17)
`0.28411 (10)
`0.2843
`0.28565 (10)
`0.28158 (9)
`0.2795
`0.28234 (10)
`0.28461 (10)
`0.2858
`0.23842 (2)
`0.09137 (7)
`0.31520 (8)
`0.3902 (19)
`0.26391 (8)
`0.28676 (8)
`0.59788 (2)
`0.49521 (8)
`0.4300 (18)
`0.73507 (8)
`0.7526 (10)
`0.57479 (8)
`0.59985 (9)
`0.78679 (8)
`0.8624 (15)
`0.7308 (17)
`1.04601 (8)
`1.0714 (18)
`1.1091 (15)
`0.91292 (8)
`0.8480 (15)
`0.9680 (16)
`
`0.137 (2)
`0.2424 (15)
`0.04801 (11)
`0.1345
`−0.09510 (11)
`−0.11349 (11)
`−0.1547
`0.03715 (12)
`−0.18892 (12)
`−0.2969
`0.41894 (3)
`0.45148 (9)
`0.55501 (9)
`0.5380 (10)
`0.42577 (8)
`0.26682 (9)
`0.42266 (3)
`0.52280 (9)
`0.4769 (15)
`0.50517 (10)
`0.5008 (18)
`0.43008 (9)
`0.26114 (9)
`0.52112 (11)
`0.502 (2)
`0.484 (2)
`0.44288 (10)
`0.4441 (19)
`0.481 (2)
`0.75025 (9)
`0.699 (2)
`0.6944 (19)
`
`0.4966 (12)
`0.3916 (15)
`0.23314 (8)
`0.1942
`0.18257 (9)
`0.37482 (8)
`0.4443
`0.34900 (9)
`0.27069 (10)
`0.2636
`0.11253 (2)
`0.04480 (7)
`0.07195 (7)
`0.0918 (15)
`0.25172 (7)
`0.07706 (7)
`0.46934 (2)
`0.37270 (7)
`0.3450 (15)
`0.48323 (7)
`0.4177 (17)
`0.59371 (7)
`0.42328 (7)
`0.77991 (8)
`0.7733 (18)
`0.7240 (15)
`0.79982 (7)
`0.8747 (12)
`0.7840 (17)
`0.58426 (8)
`0.5712 (17)
`0.5732 (17)
`
`0.019*
`0.019*
`0.01377 (16)
`0.017*
`0.01465 (17)
`0.01238 (16)
`0.015*
`0.01169 (17)
`0.01394 (18)
`0.017*
`0.00876 (5)
`0.01176 (13)
`0.01273 (14)
`0.019*
`0.01225 (14)
`0.01314 (14)
`0.00962 (5)
`0.01584 (15)
`0.024*
`0.01466 (14)
`0.022*
`0.01269 (14)
`0.01614 (15)
`0.01834 (16)
`0.028*
`0.028*
`0.01506 (15)
`0.023*
`0.023*
`0.01633 (15)
`0.025*
`0.025*
`
`Atomic displacement parameters (Å2)
`
`U11
`
`0.0286 (5)
`0.0231 (4)
`0.0212 (4)
`0.0176 (4)
`0.0142 (4)
`0.0177 (4)
`0.0291 (5)
`0.0207 (4)
`0.0207 (4)
`0.0169 (4)
`0.0139 (4)
`0.0172 (4)
`
`N1A
`N2A
`N3A
`N4A
`C1A
`C2A
`N1B
`N2B
`N3B
`N4B
`C1B
`C2B
`
`U22
`
`0.0117 (4)
`0.0110 (4)
`0.0128 (4)
`0.0118 (4)
`0.0125 (5)
`0.0134 (5)
`0.0157 (4)
`0.0123 (4)
`0.0154 (4)
`0.0105 (4)
`0.0119 (4)
`0.0154 (5)
`
`U33
`
`0.0144 (4)
`0.0115 (4)
`0.0127 (4)
`0.0114 (4)
`0.0123 (5)
`0.0134 (5)
`0.0145 (4)
`0.0155 (4)
`0.0154 (4)
`0.0129 (4)
`0.0146 (5)
`0.0139 (5)
`
`U12
`
`−0.0010 (4)
`−0.0008 (3)
`−0.0002 (3)
`0.0000 (3)
`−0.0003 (3)
`−0.0004 (4)
`−0.0063 (4)
`−0.0025 (3)
`−0.0004 (3)
`−0.0015 (3)
`−0.0004 (3)
`−0.0002 (4)
`
`U13
`
`0.0086 (4)
`0.0067 (3)
`0.0067 (3)
`0.0054 (3)
`0.0041 (3)
`0.0061 (4)
`0.0085 (4)
`0.0063 (3)
`0.0058 (3)
`0.0045 (3)
`0.0037 (3)
`0.0048 (4)
`
`U23
`
`−0.0005 (3)
`0.0012 (3)
`−0.0007 (3)
`0.0021 (3)
`0.0017 (3)
`0.0002 (3)
`−0.0010 (3)
`−0.0011 (3)
`−0.0014 (3)
`−0.0001 (3)
`0.0000 (3)
`−0.0006 (4)
`
`Acta Cryst. (2012). E68, o3257–o3258
`
`sup-7
`
`Merck Exhibit 2215, Page 9
`Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.
`IPR2020-00040
`
`

`

`supporting information
`
`N1C
`N2C
`N3C
`N4C
`C1C
`C2C
`P1A
`O1A
`O2A
`O3A
`O4A
`P1B
`O1B
`O2B
`O3B
`O4B
`O1
`O2
`O3
`
`0.0248 (4)
`0.0222 (4)
`0.0225 (4)
`0.0167 (4)
`0.0135 (4)
`0.0186 (5)
`0.01123 (10)
`0.0118 (3)
`0.0126 (3)
`0.0152 (3)
`0.0200 (3)
`0.01187 (10)
`0.0154 (3)
`0.0131 (3)
`0.0136 (3)
`0.0291 (4)
`0.0131 (3)
`0.0152 (3)
`0.0162 (3)
`
`0.0124 (4)
`0.0099 (4)
`0.0101 (4)
`0.0104 (4)
`0.0112 (5)
`0.0113 (4)
`0.00815 (11)
`0.0126 (3)
`0.0103 (3)
`0.0137 (3)
`0.0094 (3)
`0.00900 (11)
`0.0138 (4)
`0.0193 (4)
`0.0160 (4)
`0.0099 (3)
`0.0292 (5)
`0.0208 (4)
`0.0120 (4)
`
`0.0129 (4)
`0.0106 (4)
`0.0123 (4)
`0.0109 (4)
`0.0107 (4)
`0.0126 (4)
`0.00727 (11)
`0.0107 (3)
`0.0161 (4)
`0.0078 (3)
`0.0113 (3)
`0.00812 (11)
`0.0150 (4)
`0.0127 (3)
`0.0095 (3)
`0.0115 (3)
`0.0127 (4)
`0.0099 (3)
`0.0225 (4)
`
`−0.0016 (3)
`0.0010 (3)
`0.0017 (3)
`−0.0008 (3)
`−0.0004 (3)
`0.0005 (4)
`0.00019 (8)
`0.0004 (3)
`0.0001 (3)
`0.0001 (3)
`0.0015 (3)
`−0.00035 (8)
`−0.0008 (3)
`−0.0036 (3)
`−0.0003 (3)
`−0.0003 (3)
`−0.0018 (3)
`−0.0028 (3)
`−0.0001 (3)
`
`0.0079 (3)
`0.0070 (3)
`0.0066 (3)
`0.0054 (3)
`0.0040 (3)
`0.0056 (4)
`0.00335 (8)
`0.0031 (2)
`0.0057 (3)
`0.0034 (3)
`0.0067 (3)
`0.00319 (8)
`−0.0006 (3)
`0.0057 (3)
`0.0051 (3)
`0.0093 (3)
`0.0039 (3)
`0.0047 (3)
`0.0083 (3)
`
`−0.0013 (3)
`0.0005 (3)
`0.0002 (3)
`0.0008 (3)
`0.0008 (3)
`0.0006 (3)
`0.00021 (8)
`0.0007 (3)
`0.0030 (3)
`−0.0008 (2)
`−0.0003 (3)
`−0.00054 (8)
`0.0036 (3)
`−0.0023 (3)
`−0.0022 (3)
`−0.0011 (3)
`−0.0045 (3)
`−0.0007 (3)
`−0.0010 (3)
`
`Geometric parameters (Å, º)
`
`N1A—C1A
`N1A—H1A1
`N1A—H1A2
`N2A—C1A
`N2A—N3A
`N2A—H2A
`N3A—C2A
`N4A—C1A
`N4A—C2A
`N4A—H4A
`C2A—H2AA
`N1B—C1B
`N1B—H1B1
`N1B—H1B2
`N2B—C1B
`N2B—N3B
`N2B—H2B1
`N3B—C2B
`N4B—C1B
`N4B—C2B
`N4B—H4B
`C2B—H2B2
`N1C—C1C
`N1C—H1C1
`N1C—H1C2
`
`1.3325 (14)
`0.854 (13)
`0.849 (13)
`1.3353 (14)
`1.3826 (13)
`0.8800
`1.3022 (14)
`1.3504 (15)
`1.3732 (14)
`0.8800
`0.9500
`1.3272 (15)
`0.859 (13)
`0.820 (13)
`1.3401 (14)
`1.3888 (14)
`0.8800
`1.3018 (15)
`1.3524 (14)
`1.3706 (14)
`0.8800
`0.9500
`1.3304 (14)
`0.833 (13)
`0.855 (13)
`
`N2C—C1C
`N2C—N3C
`N2C—H2C
`N3C—C2C
`N4C—C1C
`N4C—C2C
`N4C—H4C
`C2C—H2CA
`P1A—O4A
`P1A—O1A
`P1A—O3A
`P1A—O2A
`O2A—H2AB
`P1B—O4B
`P1B—O3B
`P1B—O1B
`P1B—O2B
`O1B—H1B
`O2B—H2BA
`O1—H1D
`O1—H1E
`O2—H2D
`O2—H2E
`O3—H3D
`O3—H3E
`
`1.3361 (13)
`1.3838 (13)
`0.8800
`1.3044 (14)
`1.3537 (14)
`1.3724 (14)
`0.8800
`0.9500
`1.5243 (8)
`1.5294 (8)
`1.5364 (8)
`1.5845 (8)
`0.7639
`1.5132 (8)
`1.5163 (8)
`1.5612 (8)
`1.5741 (8)
`0.7742
`0.8262
`0.835 (14)
`0.796 (14)
`0.819 (13)
`0.808 (13)
`0.790 (13)
`0.795 (13)
`
`Acta Cryst. (2012). E68, o3257–o3258
`
`sup-8
`
`Merck Exhibit 2215, Page 10
`Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.
`IPR2020-00040
`
`

`

`supporting information
`
`C1A—N1A—H1A1
`C1A—N1A—H1A2
`H1A1—N1A—H1A2
`C1A—N2A—N3A
`C1A—N2A—H2A
`N3A—N2A—H2A
`C2A—N3A—N2A
`C1A—N4A—C2A
`C1A—N4A—H4A
`C2A—N4A—H4A
`N1A—C1A—N2A
`N1A—C1A—N4A
`N2A—C1A—N4A
`N3A—C2A—N4A
`N3A—C2A—H2AA
`N4A—C2A—H2AA
`C1B—N1B—H1B1
`C1B—N1B—H1B2
`H1B1—N1B—H1B2
`C1B—N2B—N3B
`C1B—N2B—H2B1
`N3B—N2B—H2B1
`C2B—N3B—N2B
`C1B—N4B—C2B
`C1B—N4B—H4B
`C2B—N4B—H4B
`N1B—C1B—N2B
`N1B—C1B—N4B
`N2B—C1B—N4B
`N3B—C2B—N4B
`N3B—C2B—H2B2
`N4B—C2B—H2B2
`C1C—N1C—H1C1
`
`113.9 (12)
`119.3 (12)
`120.2 (17)
`111.07 (9)
`124.5
`124.5
`104.11 (9)
`106.34 (9)
`126.8
`126.8
`125.90 (10)
`127.52 (10)
`106.56 (9)
`111.92 (10)
`124.0
`124.0
`118.9 (12)
`120.0 (13)
`120.2 (18)
`110.80 (9)
`124.6
`124.6
`103.98 (9)
`106.33 (9)
`126.8
`126.8
`127.37 (10)
`126.03 (10)
`106.60 (10)
`112.29 (10)
`123.9
`123.9
`119.1 (12)
`
`C1C—N1C—H1C2
`H1C1—N1C—H1C2
`C1C—N2C—N3C
`C1C—N2C—H2C
`N3C—N2C—H2C
`C2C—N3C—N2C
`C1C—N4C—C2C
`C1C—N4C—H4C
`C2C—N4C—H4C
`N1C—C1C—N2C
`N1C—C1C—N4C
`N2C—C1C—N4C
`N3C—C2C—N4C
`N3C—C2C—H2CA
`N4C—C2C—H2CA
`O4A—P1A—O1A
`O4A—P1A—O3A
`O1A—P1A—O3A
`O4A—P1A—O2A
`O1A—P1A—O2A
`O3A—P1A—O2A
`P1A—O2A—H2AB
`O4B—P1B—O3B
`O4B—P1B—O1B
`O3B—P1B—O1B
`O4B—P1B—O2B
`O3B—P1B—O2B
`O1B—P1B—O2B
`P1B—O1B—H1B
`P1B—O2B—H2BA
`H1D—O1—H1E
`H2D—O2—H2E
`H3D—O3—H3E
`
`115.6 (11)
`124.9 (16)
`110.88 (9)
`124.6
`124.6
`104.11 (9)
`106.08 (9)
`127.0
`127.0
`125.74 (10)
`127.44 (10)
`106.81 (9)
`112.11 (10)
`123.9
`123.9
`113.13 (4)
`110.03 (4)
`110.70 (4)
`109.97 (5)
`103.52 (4)
`109.26 (4)
`109.5
`112.98 (5)
`110.95 (5)
`111.80 (5)
`110.94 (5)
`106.50 (4)
`103.13 (5)
`109.5
`109.5
`109.7 (19)
`101.5 (17)
`104.3 (18)
`
`Hydrogen-bond geometry (Å, º)
`
`D—H···A
`N1A—H1A1···O3B
`N1A—H1A2···N3Ai
`N2A—H2A···O4B
`N4A—H4A···O4Bi
`N1B—H1B1···O2
`N1B—H1B2···N3Bi
`N2B—H2B1···O3ii
`N4B—H4B···O1Aiii
`N1C—H1C1···N3Ci
`N1C—H1C2···O3A
`N2C—H2C···O4A
`
`D—H
`
`0.85 (1)
`0.85 (1)
`0.88
`0.88
`0.86 (1)
`0.82 (1)
`0.88
`0.88
`0.83 (1)
`0.86 (1)
`0.88
`
`H···A
`
`2.31 (1)
`2.19 (1)
`1.77
`1.76
`1.96 (1)
`2.28 (1)
`1.84
`1.87
`2.18 (1)
`2.24 (1)
`1.78
`
`D···A
`
`3.1356 (13)
`3.0305 (15)
`2.6130 (13)
`2.6314 (13)
`2.8214 (13)
`3.0639 (15)
`2.6824 (13)
`2.7376 (12)
`3.0028 (14)
`3.0589 (13)
`2.6278 (12)
`
`D—H···A
`
`162 (2)
`170 (2)
`161
`171
`178 (2)
`160 (2)
`159
`167
`172 (2)
`160 (2)
`161
`
`Acta Cryst. (2012). E68, o3257–o3258
`
`sup-9
`
`Merck Exhibit 2215, Page 11
`Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.
`IPR2020-00040
`
`

`

`N4C—H4C···O4Ai
`O2A—H2AB···O3Biv
`O1B—H1B···O3A
`O2B—H2BA···O1iv
`O1—H1D···O2
`O1—H1E···O3B
`O2—H2D···O1Av
`O2—H2E···O3Aiii
`O3—H3D···O2B
`O3—H3E···O1Aiii
`
`supporting information
`
`0.88
`0.76
`0.77
`0.83
`0.84 (1)
`0.80 (1)
`0.82 (1)
`0.81 (1)
`0.79 (1)
`0.80 (1)
`
`1.79
`1.95
`1.80
`1.73
`1.93 (1)
`1.91 (1)
`1.90 (1)
`1.95 (1)
`2.14 (2)
`1.92 (1)
`
`2.6645 (12)
`2.6593 (11)
`2.5495 (12)
`2.5552 (12)
`2.7439 (12)
`2.6968 (12)
`2.7024 (11)
`2.7566 (12)
`2.8515 (12)
`2.7085 (11)
`
`170
`155
`161
`176
`166 (2)
`168 (2)
`168 (2)
`178 (2)
`149 (2)
`176 (2)
`
`Symmetry codes: (i) x, −y, z+1/2; (ii) x, y−1, z; (iii) x+1, −y+1, z+1/2; (iv) x, −y+1, z−1/2; (v) x+1, y, z+1.
`
`Acta Cryst. (2012). E68, o3257–o3258
`
`sup-10
`
`Merck Exhibit 2215, Page 12
`Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.
`IPR2020-00040
`
`