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`Merck Exhibit 2211, Page 1
`Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.
`IPR2020-00040
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`M. T. AVERBUCH-POUCHOT AND A. DURIF 1895 0.03 ° s -~, total background measuring time 10 s. Two intensity and orientation reference reflexions (130 and 130) measured every 2 h without significant variation. Lorentz and polarization correction, no absorption correction. Structure solved by classical methods (Pat- terson and successive Fourier syntheses). H atoms from difference Fourier map. Anisotropic full-matrix least- squares refinement (on F), isotropic for H atoms. Unit weights. Final refinement cycles with 1499 reflexions corresponding to I> 9a r Final R =0.038 (wR = 0-043). S = 1.485. Max. A/a= 0.06 [B of H(2N2)I. c ~ -'~'~---~o~ ol2) Fig. 1. Projection along the a direction of the atomic arrangement of HPO4(NH3)2(CH2)2. bl ...... HI3N21 H(2N 1 ) Fig. 2. Projection along the e direction of the atomic arrangement of HAsO4(NH3)2(CH2)2. Table 1. Final atomic coordinates, Beqfor non-H atoms and Bisofor H atoms in HPO4(NH3)2(CH2) z x y z Beq/Blso(A 2) P 0.24191 (7) 0.13601 (5) 0.08489 (7) 1.126 (8) O(1) 0.9061 (2) 0-8820 (1) 0.8223 (2) 2.00 (3) O(2) 0.6426 (2) 0.9694 (I) 0.8584 (2) 1.67 (3) 0(3) 0.3473 (2) 0.6450 (2) 0.1307 (2) 1.72 (3) 0(4) 0.8422 (2) 0.2559 (1) 0.1652 (2) 1.97 (3) N(I) 0.2861 (2) 0.9430 (2) 0.7436 (3) 1.64 (4) N(2) 0.2211 (2) 0.8427 (2) 0.2487 (2) 1.58 (4) O(1) 0.2814 (3) 0.4394 (2) 0.4646 (3) 2.18 (5) 0(2) 0.2926 (3) 0.8410 (2) 0.4593 (3) 1-85 (5) H 0.042 (5) 0.166 (4) 0.183 (6) 6.6 (12) H(IC 1) 0.919 (5) 0.060 (4) 0.524 (6) 6.3 (11) H(2C 1) 0.738 (5) 0.494 (3) 0.484 (5) 4.1 (8) H(IC2) 0.726 (4) 0.227 (3) 0.493 (4) 3.3 (8) H(2C2) 0.073 (4) 0.338 (3) 0.499 (5) 4.2 (8) H(1NI) 0-749(3) 0.114(3) 0.219(4) 2.1 (6) H(2N1) 0.101 (4) 0.457 (3) 0.236 (5) 3-9 (8) H(3NI) 0.262 (4) 0.505 (3) 0.221 (4) 2-9 (7) H(IN2) 0.238 (4) 0.280 (3) 0.790 (4) 3.1 (7) H(2N2) 0.219 (4) 0.415 (3) 0.791 (5) 4.4 (9) H(3N2) 0.402 (4) 0.343 (3) 0.780 (5) 4.0 (8) Table 2. Final atomic coordinates, Beqfor non-H atoms and Buo for H atoms in HAsO4(NH3)E(CH2) z se. = ] Z, YA.aj~u. X y z Beq/Biso(A 2) As 0.24979 (5) 0.06941 (6) 0.09305 (6) 1.212 (9) O(1) 0.2323 (3) 0.8743 (4) 0.1546 (4) 1.60 (8) 0(2) 0.7903 (5) 0.5566 (5) 0.6155 (4) 2.9 (1) 0(3) 0.1847 (4) 0.3050 (5) 0.6909 (5) 2.4 (I) 0(4) 0.5991 (4) 0.6297 (5) 0.3887 (5) 2.3 (1) N(I) 0.0816 (4) 0.6939 (5) 0.9306 (5) 1.51 (9) N(2) 0.5379 (4) 0.1983 (6) 0.3905 (5) 1.8 (1) C(I) 0.9449 (5) 0.4517 (6) 0.9660 (6) 1.8 (1) C(2) 0.4375 (5) 0.5402 (6) 0.0247 (6) 1.9 (1) H 0.211 (6) 0.388 (8) 0.328 (8) 3. (1) H(1C1) 0.009 (10) 0.597 (14) 0.136 (12) 8. (3) H(2C1) 0.876 (8) 0.498 (11) 0.975 (10) 5. (2) H(1C2) 0.622 (11) 0.060 (5) 0.549 (13) 8. (3) H(2C2) 0.606 (6) 0.539 (8) 0.907 (8) 3. (1) H(1N1) -0.022 (6) 0.216 (8) 0.574 (8) 2. (1) H(2N1) 0.125 (6) 0.744 (8) 0.488 (7) 2. (1) H(3N1) 0.878 (6) 0.159 (7) 0.658 (7) 1. (1) H(IN2) 0.497 (9) 0.340 (11) 0.822 (10) 6. (2) H(ZN2) 0.607 (5) 0.287 (7) 0.861 (7) 1- (1) H(3N2) 0.485 (6) 0.254 (8) 0.454 (7) 2. (1) Max. peak height in final difference Fourier synthesis 1.97 e A -3. No extinction correction, R = 0.039 for the complete set of 2804 reflexions. Scattering factors for neutral atoms and f',f" from International Tables for X-ray Crystallography (1974). Enraf-Nonius (1977) SDP used for all calculations. Computer: PDP 11/70. Discussion. Examination of the results obtained from the crystal structure determinations shows clearly that these two compounds are not simple adducts, i.e., H3XO4.(NH2)2(CH2) 2, but have atomic arrangements built up by a stacking of HXO4 2- and (NH3)2(CH2)] +
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`Merck Exhibit 2211, Page 2
`Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.
`IPR2020-00040
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`1896 2-I- 2-- C2HloN 2 .HPO 4 AND C2HloN22+.HAsO4 2- Table 3. Main interatomic distances (A) and bond angles (o) in HPO4(NH3)2(CH2) 2 PO 4 tetrahedron P O(1) 0(2) 0(3) 0(4) O(1) 1.590 (2) 2.459 (3) 2.540 (3) 2.523 (3) 0(2) 104.3 (1) 1.525 (2) 2.532 (3) 2.535 (3) O(3) 108.8 (1) 111.8 (1) 1.533 (2) 2.512 (3) 0(4) 108.4 (1) 112.7 (1) 110.7 (1) 1.521 (2) P-O = 1.542 (2) NH3-(CH2)2-NH 3 group N(1)--C(1) 1.469 (4) N(1)-C(1)--C(2) 112.1 (3) C(1)-C(2) 1.507 (4) C(1)--C(2)-N(2) 109.6 (2) C(2)--N(2) 1.486 (4) Hydrogen bonds (O,N)-H H...O (O,N)--O L(O,N)--H...O O(I)-H-..O(4) 0.71 (6) 1.90 (6) 2.578 (3) 160 (7) N(1)-H(IN1)--.O(4) 0.82 (4) 1.93 (4) 2.747 (4) 173 (4) N(I)--H(2N1)...O(2) 0.88 (5) 1.85 (5) 2.719 (4) 167 (5) N(I)-H(3N1)...O(3) 0.91 (4) 2.00(5) 2.906 (4) 176 (4) N(2)-H(1N2)...O(3) 0.90 (4) 1.91 (5) 2.810(4) 178 (4) N(2)--H(2N2)...O(2) 1.08 (5) 1.65 (5) 2.720 (4) 176 (4) N(2)--H(3N2)...0(3) 0.94 (5) 1.90 (5) 2.836 (4) 172 (4) Table 4. Main interatomic distances (A) and bond angles (o) in HAsO4(NH3)2(CH2) 2 AsO 4 tetrahedron As O(1) 0(2) 0(3) 0(4) O(I) 1.678 (3) 2.647 (4) 2.775 (4) 2.751 (4) 0(2) 101.7 (2) 1.734 (3) 2.793 (5) 2.763 (5) 0(3) 111.9 (2) 110.2 (2) 1.672 (3) 2.763 (5) 0(4) 111.1 (2) 109.1 (2) 112.2 (2) 1.657 (3) As-O = 1.685 (3) NH3-(CH2)2--NH 3 groups C(1)-C(1) C(1)-N(1) C(1)--C (1)---N(1) Hydrogen bonds 1.496 (8) C(2)-C(2) 1.516 (9) 1.479 (5) C(2)-N(2) 1.482 (6) 111.3 (4) C(2)-C(2)-N(2) 110.6 (5) (O,N)-H H...O (O,N)-O/(O,N)--H...O O(2)-H...O(3) 0.64 (6) 2.03 (6) 2.634 (5) 158 (8) N(1)-H(1N1)...O(3) 0.64 (6) 2.14 (6) 2.744 (5) 157 (7) N(1)--H(2N1)...O(1) 0.82 (6) 1.99 (6) 2.805 (5) 170 (5) N(1)--H(3N1)...O(1) 0.88 (5) 1.92 (5) 2.788 (5) 168 (5) N(2)--H(1N2)...O(4) 0.76 (8) 1.98 (8) 2.718 (5) 162 (8) N(2)-H(2N2)...O(1) 0.77 (5) 2.14 (6) 2.820 (5) 148 (5) N(2)-H(3N2)...O(4) 0.88 (6) 1.81 (6) 2.686 (5) 170 (5) groups. In both structures one observes a layer arrangement: planes of HXOa tetrahedra alternate with planes of (CH2)2(NH3) 2+ groups, as depicted in Figs. 1 and 2. Another common feature for these two arrangements is the internal repartition of the HXO 2- tetrahedra in their planes; they are associated in pairs forming H2X208 clusters with rather short X-X distances (P--P = 4.847, As-As = 4.994 A). The two HXO a groups in such a cluster are linked by a double hydrogen bridge. In the case of the phosphorus compound the (NHa)2(CH2) 2 entities are strongly pseudocentro- symmetric while they are centrosymmetric in the arsenic compound. This implies the existence of two crystallographicaUy independent (NHa)2(CH2) 2 units. Tables 1 and 2* report the final atomic coordinates, while Tables 3 and 4 give the main interatomic distances, bond angles and details of the hydrogen-bond scheme. * Lists of structure factors, anisotropic thermal parameters and bond distances and angles involving H atoms have been deposited with the British Library Document Supply Centre as Supplemen- tary Publication No. SUP 44090 (27 pp.). Copies may be obtained through The Executive Secretary, International Union of Crystal- lography, 5 Abbey Square, Chester CH 1 2HU, England. References Enraf-Nonius (1977). Structure Determination Package. Enraf- Nonius, Delft, The Netherlands. International Tables for X-ray Crystallography (1974). Vol. IV. Birmingham: Kynoch Press. (Present distributor D. Reidel, Dordrecht.) Acta Cryst. (1987). C43, 1896-1898 / Structure of Disodium Ethylenediammonium Bis[monohydrogentetraoxophosphate(V)] Hexahydrate BY M. T. AVERBUCH-POUCHOT, A. DURIF AND J. C. GUITEL Laboratoire de Cristallographie, Centre National de la Recherche Scientifique, Laboratoire associ~ ~ I'USTMG, 166X, 38042 Grenoble CEDEX, France (Received 18 March 1987; accepted 22 May 1987) Abstract. C2H~oN2+.2Na+.2HPOe-.6H2 O, Mr = 408.15, monoclinic, P21/c , a -- 11.699 (9), b = 10.164 (9), c = 6.835 (4) A, fl= 105.00 (5) °, V= 785 (2) A 3, z = 2, D x = 1.727 Mg m -3, 2(Mo Kct) = 0108-2701/87/101896-03501.50 0.7107 A, a = 0.415 mm -1, F(000) = 428, T-- 295 K, final R=0.022 for 1823 independent reflexions. HPO 2- and (CH2)2(NHa) 2+ groups alternate in planes perpendicular to the a axis. In these planes, HPO 2- © 1987 International Union of Crystallography
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`Merck Exhibit 2211, Page 3
`Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.
`IPR2020-00040
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