Bis[(2,2-dimethyl­propano­yloxy)meth­yl] {[2-(6-amino-9H-purin-9-yl)eth­oxy]meth­yl}phospho­nate–succinic acid (2/1)

Jung, S.; Ha, J.-M.; Kim, I.W.

doi:10.1107/S1600536812006873

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 68| Part 3| March 2012| Pages o809-o810

doi:10.1107/S1600536812006873

Open

access

Bis[(2,2-dimethylpropanoyloxy)methyl] {[2-(6-amino-9H-purin-9-yl)ethoxy]methyl}phosphonate–succinic acid (2/1)

Sungyup Jung,^a Jeong-Myeong Ha ^b and Il Won Kim ^a ^*

^aDepartment of Chemical Engineering, Soongsil University, 369 Sangdo-ro, Dongjak-gu, Seoul 156-743, Republic of Korea, and ^bKorea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea
^*Correspondence e-mail: iwkim@ssu.ac.kr

(Received 21 January 2012; accepted 15 February 2012; online 24 February 2012)

The title compound, C₂₀H₃₂N₅O₈P·0.5C₄H₆O₄, is composed of two 9-{2-[bis(pivaloyloxymethoxy)phosphinylmethoxy]ethyl}adenine, commonly known as adefovir dipivoxil (AD), molecules linked to the carboxylic acid groups of succinic acid (SA). The asymmetric unit contains one molecule of AD and half a molecule of SA, which sits on an inversion center. Both adenine units in the two AD molecules make AD–SA N—H⋯O and SA–AD O—H⋯N hydrogen bonds to SA. In addition, the intermolecular AD–AD N—H⋯O—P hydrogen bond serves to stabilize the cocrystal. There is also a π–π stacking interaction [interplanar spacing 3.34 (19) Å] between adjacent inversion-related adenine groups.

Related literature

For the synthesis and process optimization of 9-{2-[bis(pivaloyloxymethoxy)phosphinylmethoxy]ethyl}adenine, see: Starrett et al. (1992 ); Yu et al. (1999 ). For the biological and pharmacological relevance of 9-{2-[bis(pivaloyloxymethoxy)phosphinylmethoxy]ethyl}adenine, see: Qaqish et al. (2003 ); Julander et al. (2002 ). For the structure of a hydrate of the title compound, see: Chang et al. (2007 ).

Experimental

Crystal data

C₂₀H₃₂N₅O₈P·0.5C₄H₆O₄
M_r = 560.52
Triclinic, $[P \overline 1]$
a = 7.7122 (12) Å
b = 10.1577 (15) Å
c = 19.185 (3) Å
α = 80.409 (8)°
β = 79.718 (9)°
γ = 80.407 (8)°
V = 1443.5 (4) Å³
Z = 2
Mo Kα radiation
μ = 0.15 mm⁻¹
T = 296 K
0.11 × 0.10 × 0.08 mm

Data collection

Bruker SMART CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2002 ) T_min = 0.982, T_max = 0.987
49737 measured reflections
7222 independent reflections
4593 reflections with I > 2σ(I)
R_int = 0.053

Refinement

R[F² > 2σ(F²)] = 0.046
wR(F²) = 0.143
S = 1.01
7222 reflections
417 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.38 e Å⁻³
Δρ_min = −0.29 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1C⋯O1ⁱ	0.812 (19)	2.14 (2)	2.941 (2)	170.16 (18)
N1—H1B⋯O9	0.79 (2)	2.05 (2)	2.842 (2)	175 (2)
O10—H10⋯N4	0.84 (2)	1.91 (2)	2.734 (2)	166 (2)
Symmetry code: (i) x+1, y-1, z.

Data collection: SMART (Bruker, 2002); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ); software used to prepare material for publication: WinGX (Farrugia, 1999 ).

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536812006873/pk2386sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536812006873/pk2386Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536812006873/pk2386Isup3.cml

checkCIF report

Comment top

9-{2-[Bis(pivaloyloxymethoxy)phosphinylmethoxy]ethyl}adenine, also known as adefovir dipivoxil (AD), is a broad-spectrum antiviral from the class of acyclic nucleoside phosphonates. It is an orally bioavailable prodrug of 9-[2-(phosphonylmethoxy)ethyl] adenine, which acts as a chain terminator nucleotide analogue and is effective against the human immunodeficiency virus, herpes viruses, Epstein–Barr virus, retroviruses, cytomegalovirus, and other DNA viruses (Yu et al., 1999; Julander et al., 2002; Qaqish et al., 2003). In the present study, we report a new cocrystal of AD with succinic acid to later study the physical characteristics, such as thermal stability and in vitro release behavior.

Related literature top

For the synthesis and process optimization of 9-{2-[bis(pivaloyloxymethoxy)phosphinylmethoxy]ethyl}adenine, see: Starrett et al. (1992); Yu et al. (1999). For the biological and pharmacological relevance of 9-{2-[bis(pivaloyloxymethoxy)phosphinylmethoxy]ethyl}adenine, see: Qaqish et al. (2003); Julander et al. (2002). For the structure of a hydrate of the title compound, see: Chang et al. (2007).

Experimental top

The title compound was formed during cocrystallization in a 2:1 molar ratio of 9-{2-[bis(pivaloyloxymethoxy)phosphinylmethoxy]ethyl}adenine, commonly known as adefovir dipivoxil, (0.4 mmol, AMoRe Pacific Co., purity > 99%) and succinic acid (0.2 mmol, Sigma–Aldrich, purity > 99%). The two components were dissolved in ethanol (3 ml, Samchun Chemical, Korea, HPLC grade) and heated at 45–50°C for 1 h. The prepared solution was stored in a 25°C incubator, and the crystals were started to be visible after about 1 d. After 2 more weeks, the crystals were filtered, washed with deionized water (Resistivity > 18.2 MΩ-cm; Direct-Q, Millipore), and dried for 24 h in a 40°C vacuum oven.

Computing details top

Data collection: SMART (Bruker, 2002); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT (Bruker, 2002); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top

	Fig. 1. The molecular structure of the title compound, showing 20% probability displacement ellipsoids. H atoms are shown as small spheres of arbitrary radius. Intermolecular interactions are shown as dashed lines. [Symmetry code: (i) -x + 2, -y - 1, -z].
	Fig. 2. Crystal packing diagram for the title compound. For clarity, H atoms are shown only for those involved in hydrogen bonding (dashed lines).

Bis[(2,2-dimethylpropanoyloxy)methyl] {[2-(6-amino-9H-purin-9-yl)ethoxy]methyl}phosphonate–succinic acid (2/1) top

Crystal data top

C₂₀H₃₂N₅O₈P·0.5C₄H₆O₄	Z = 2
M_r = 560.52	F(000) = 594
Triclinic, P1	D_x = 1.290 Mg m⁻³
Hall symbol: -P 1	Melting point: 410 K
a = 7.7122 (12) Å	Mo Kα radiation, λ = 0.71073 Å
b = 10.1577 (15) Å	Cell parameters from 9846 reflections
c = 19.185 (3) Å	θ = 2.2–25.7°
α = 80.409 (8)°	µ = 0.15 mm⁻¹
β = 79.718 (9)°	T = 296 K
γ = 80.407 (8)°	Block, colourless
V = 1443.5 (4) Å³	0.11 × 0.10 × 0.08 mm

Data collection top

Bruker SMART CCD diffractometer	7222 independent reflections
Radiation source: fine-focus sealed tube	4593 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.053
ϕ and ω scans	θ_max = 28.4°, θ_min = 1.1°
Absorption correction: multi-scan (SADABS; Bruker, 2002)	h = −10→10
T_min = 0.982, T_max = 0.987	k = −13→13
49737 measured reflections	l = −25→25

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.046	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.143	H atoms treated by a mixture of independent and constrained refinement
S = 1.01	w = 1/[σ²(F_o²) + (0.0783P)²] where P = (F_o² + 2F_c²)/3
7222 reflections	(Δ/σ)_max < 0.001
417 parameters	Δρ_max = 0.38 e Å⁻³
0 restraints	Δρ_min = −0.29 e Å⁻³

Crystal data top

C₂₀H₃₂N₅O₈P·0.5C₄H₆O₄	γ = 80.407 (8)°
M_r = 560.52	V = 1443.5 (4) Å³
Triclinic, P1	Z = 2
a = 7.7122 (12) Å	Mo Kα radiation
b = 10.1577 (15) Å	µ = 0.15 mm⁻¹
c = 19.185 (3) Å	T = 296 K
α = 80.409 (8)°	0.11 × 0.10 × 0.08 mm
β = 79.718 (9)°

Data collection top

Bruker SMART CCD diffractometer	7222 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2002)	4593 reflections with I > 2σ(I)
T_min = 0.982, T_max = 0.987	R_int = 0.053
49737 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.046	0 restraints
wR(F²) = 0.143	H atoms treated by a mixture of independent and constrained refinement
S = 1.01	Δρ_max = 0.38 e Å⁻³
7222 reflections	Δρ_min = −0.29 e Å⁻³
417 parameters

Special details top

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) top

	x	y	z	U_iso*/U_eq
P1	0.85354 (6)	0.35488 (4)	0.23364 (3)	0.04127 (14)
O2	1.16908 (15)	0.27477 (11)	0.16611 (7)	0.0465 (3)
H22A	0.869 (3)	−0.400 (2)	0.0252 (13)	0.083 (8)*
O1	0.75924 (17)	0.37739 (12)	0.17242 (7)	0.0520 (3)
H7A	1.410 (3)	0.2107 (19)	0.1924 (10)	0.052 (5)*
N4	1.30471 (18)	−0.10694 (13)	0.07213 (8)	0.0408 (3)
H6A	1.364 (3)	0.2683 (19)	0.0495 (10)	0.050 (5)*
N5	1.40907 (18)	0.07897 (12)	0.08442 (7)	0.0376 (3)
H8A	1.137 (3)	0.353 (2)	0.2554 (13)	0.077 (7)*
O10	1.08166 (19)	−0.23084 (12)	0.01701 (8)	0.0561 (4)
H1C	1.590 (3)	−0.454 (2)	0.1269 (10)	0.047 (5)*
N1	1.5210 (2)	−0.38651 (15)	0.11658 (10)	0.0497 (4)
H5	1.177 (3)	0.0849 (19)	0.0460 (10)	0.054 (5)*
O6	0.79832 (17)	0.45855 (12)	0.28933 (7)	0.0545 (3)
H7B	1.377 (3)	0.371 (2)	0.1459 (10)	0.057 (5)*
O3	0.83198 (18)	0.21639 (11)	0.28310 (7)	0.0526 (3)
H6B	1.549 (3)	0.2239 (18)	0.0706 (10)	0.054 (6)*
C3	1.4627 (2)	−0.14293 (15)	0.09965 (9)	0.0350 (4)
H1A	1.870 (3)	−0.1491 (19)	0.1681 (11)	0.059 (6)*
N2	1.7135 (2)	−0.26489 (14)	0.14725 (9)	0.0508 (4)
H15B	0.551 (3)	0.523 (2)	0.2714 (12)	0.071 (7)*
N3	1.6779 (2)	−0.02193 (14)	0.13207 (9)	0.0513 (4)
H15A	0.633 (3)	0.619 (2)	0.3206 (12)	0.078 (7)*
C4	1.5280 (2)	−0.02841 (15)	0.10754 (9)	0.0372 (4)
H22B	0.974 (3)	−0.383 (2)	−0.0530 (12)	0.065 (6)*
O4	0.9500 (2)	0.00392 (13)	0.25970 (8)	0.0628 (4)
H8B	1.104 (3)	0.456 (2)	0.1946 (12)	0.073 (7)*
O7	0.5407 (2)	0.45750 (14)	0.37225 (8)	0.0645 (4)
C5	1.2792 (2)	0.02556 (16)	0.06432 (10)	0.0415 (4)
C2	1.5646 (2)	−0.26729 (15)	0.12075 (9)	0.0383 (4)
H9B	0.689 (4)	0.071 (3)	0.2924 (16)	0.112 (10)*
C6	1.4277 (3)	0.22069 (16)	0.08249 (11)	0.0438 (4)
H1B	1.438 (3)	−0.3928 (19)	0.0988 (10)	0.044 (6)*
C7	1.3572 (2)	0.27262 (18)	0.15218 (11)	0.0450 (4)
H9A	0.792 (3)	0.126 (2)	0.2055 (14)	0.088 (8)*
C22	0.9785 (3)	−0.42444 (17)	−0.00200 (12)	0.0436 (4)
H10	1.161 (3)	−0.206 (2)	0.0348 (13)	0.081 (8)*
C21	1.1118 (2)	−0.36274 (17)	0.02458 (10)	0.0445 (4)
C8	1.0864 (3)	0.3663 (2)	0.21406 (13)	0.0505 (5)
C1	1.7603 (3)	−0.14515 (19)	0.15018 (13)	0.0577 (5)
O9	1.2352 (2)	−0.42677 (14)	0.05093 (11)	0.0873 (6)
O5	0.8495 (3)	−0.0752 (3)	0.37084 (13)	0.1501 (12)
C9	0.7978 (3)	0.10227 (19)	0.25713 (16)	0.0618 (6)
C11	1.1398 (3)	−0.1700 (2)	0.31830 (12)	0.0678 (6)
C15	0.6237 (3)	0.5252 (2)	0.30718 (14)	0.0625 (6)
O8	0.4230 (3)	0.3366 (2)	0.31153 (9)	0.0959 (6)
C16	0.4436 (3)	0.3614 (2)	0.36752 (12)	0.0608 (5)
C10	0.9642 (3)	−0.0782 (2)	0.32119 (13)	0.0696 (6)
C18	0.2912 (6)	0.3830 (4)	0.4914 (2)	0.1566 (19)
H18A	0.1843	0.4337	0.4764	0.235*
H18B	0.3726	0.4436	0.4936	0.235*
H18C	0.2627	0.3324	0.5379	0.235*
C14	1.2937 (4)	−0.0882 (3)	0.28699 (18)	0.1026 (10)
H14A	1.2850	−0.0523	0.2380	0.154*
H14B	1.4052	−0.1458	0.2894	0.154*
H14C	1.2870	−0.0155	0.3140	0.154*
C12	1.1638 (5)	−0.2356 (4)	0.39287 (18)	0.1525 (18)
H12A	1.1480	−0.1675	0.4235	0.229*
H12B	1.2813	−0.2852	0.3922	0.229*
H12C	1.0774	−0.2960	0.4105	0.229*
C17	0.3749 (4)	0.2886 (3)	0.43929 (13)	0.0794 (7)
C20	0.5398 (7)	0.2122 (6)	0.4705 (3)	0.213 (3)
H20A	0.5030	0.1645	0.5170	0.320*
H20B	0.6162	0.2752	0.4746	0.320*
H20C	0.6030	0.1491	0.4395	0.320*
C19	0.2625 (9)	0.1901 (6)	0.4313 (2)	0.227 (3)
H19A	0.2433	0.1300	0.4754	0.341*
H19B	0.3207	0.1392	0.3937	0.341*
H19C	0.1501	0.2367	0.4198	0.341*
C13	1.1420 (4)	−0.2716 (3)	0.2684 (2)	0.1238 (13)
H13A	1.2543	−0.3294	0.2651	0.186*
H13B	1.1254	−0.2249	0.2217	0.186*
H13C	1.0477	−0.3249	0.2866	0.186*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
P1	0.0401 (3)	0.0328 (2)	0.0502 (3)	0.00576 (17)	−0.0116 (2)	−0.01014 (19)
O2	0.0360 (7)	0.0422 (6)	0.0663 (8)	−0.0040 (5)	−0.0069 (6)	−0.0242 (6)
O1	0.0506 (8)	0.0463 (7)	0.0587 (8)	0.0086 (6)	−0.0214 (6)	−0.0078 (6)
N4	0.0401 (8)	0.0326 (7)	0.0523 (9)	−0.0019 (6)	−0.0169 (7)	−0.0061 (6)
N5	0.0391 (8)	0.0280 (6)	0.0449 (8)	−0.0019 (5)	−0.0073 (6)	−0.0046 (6)
O10	0.0544 (9)	0.0388 (7)	0.0831 (10)	−0.0083 (6)	−0.0301 (8)	−0.0090 (6)
N1	0.0500 (10)	0.0280 (7)	0.0766 (12)	−0.0011 (7)	−0.0322 (9)	−0.0034 (7)
O6	0.0524 (8)	0.0457 (7)	0.0661 (9)	0.0058 (6)	−0.0065 (7)	−0.0249 (6)
O3	0.0654 (9)	0.0379 (6)	0.0564 (8)	−0.0030 (6)	−0.0194 (7)	−0.0062 (6)
C3	0.0367 (9)	0.0315 (8)	0.0377 (9)	−0.0033 (6)	−0.0095 (7)	−0.0054 (6)
N2	0.0493 (9)	0.0369 (8)	0.0724 (11)	0.0008 (6)	−0.0288 (8)	−0.0117 (7)
N3	0.0483 (9)	0.0385 (8)	0.0751 (11)	−0.0039 (7)	−0.0245 (8)	−0.0172 (7)
C4	0.0382 (9)	0.0317 (8)	0.0426 (9)	−0.0018 (6)	−0.0082 (7)	−0.0087 (7)
O4	0.0758 (10)	0.0428 (7)	0.0635 (9)	0.0123 (6)	−0.0158 (8)	−0.0050 (6)
O7	0.0757 (10)	0.0612 (9)	0.0554 (9)	−0.0103 (7)	0.0005 (8)	−0.0159 (7)
C5	0.0416 (10)	0.0335 (8)	0.0498 (10)	−0.0018 (7)	−0.0131 (8)	−0.0042 (7)
C2	0.0400 (9)	0.0340 (8)	0.0420 (9)	−0.0027 (7)	−0.0111 (8)	−0.0058 (7)
C6	0.0421 (11)	0.0283 (8)	0.0588 (12)	−0.0039 (7)	−0.0047 (9)	−0.0038 (8)
C7	0.0353 (10)	0.0356 (9)	0.0676 (13)	−0.0042 (7)	−0.0089 (9)	−0.0167 (9)
C22	0.0392 (10)	0.0415 (9)	0.0544 (12)	−0.0054 (8)	−0.0170 (9)	−0.0090 (8)
C21	0.0420 (10)	0.0397 (9)	0.0553 (11)	−0.0078 (7)	−0.0155 (9)	−0.0066 (8)
C8	0.0455 (11)	0.0486 (11)	0.0624 (13)	−0.0021 (9)	−0.0105 (10)	−0.0245 (10)
C1	0.0504 (12)	0.0462 (10)	0.0869 (16)	0.0009 (9)	−0.0357 (11)	−0.0201 (10)
O9	0.0812 (11)	0.0438 (8)	0.1585 (17)	−0.0067 (7)	−0.0839 (12)	−0.0076 (9)
O5	0.1080 (17)	0.147 (2)	0.1177 (18)	0.0577 (15)	0.0455 (14)	0.0593 (15)
C9	0.0713 (15)	0.0328 (9)	0.0861 (17)	0.0026 (9)	−0.0317 (14)	−0.0108 (10)
C11	0.0641 (14)	0.0598 (13)	0.0673 (14)	0.0139 (11)	−0.0086 (11)	0.0018 (11)
C15	0.0613 (14)	0.0448 (11)	0.0703 (15)	0.0110 (10)	0.0058 (12)	−0.0123 (10)
O8	0.0926 (14)	0.1482 (18)	0.0600 (11)	−0.0470 (12)	−0.0158 (10)	−0.0182 (11)
C16	0.0598 (13)	0.0672 (13)	0.0557 (13)	−0.0030 (10)	−0.0095 (11)	−0.0147 (11)
C10	0.0685 (15)	0.0583 (13)	0.0648 (15)	0.0093 (11)	0.0023 (12)	0.0085 (11)
C18	0.227 (5)	0.119 (3)	0.102 (3)	−0.060 (3)	0.081 (3)	−0.034 (2)
C14	0.0750 (19)	0.108 (2)	0.119 (2)	−0.0001 (16)	−0.0038 (17)	−0.0247 (19)
C12	0.117 (3)	0.192 (4)	0.094 (2)	0.056 (3)	−0.010 (2)	0.051 (2)
C17	0.107 (2)	0.0736 (15)	0.0561 (14)	−0.0243 (15)	0.0029 (14)	−0.0100 (12)
C20	0.201 (5)	0.230 (5)	0.145 (4)	0.024 (4)	−0.028 (4)	0.104 (4)
C19	0.361 (8)	0.261 (6)	0.110 (3)	−0.248 (6)	0.027 (4)	−0.034 (3)
C13	0.095 (2)	0.0793 (19)	0.201 (4)	0.0341 (16)	−0.047 (2)	−0.053 (2)

Geometric parameters (Å, º) top

P1—O1	1.4562 (13)	C22—H22B	1.00 (2)
P1—O3	1.5760 (13)	C21—O9	1.200 (2)
P1—O6	1.5794 (13)	C8—H8A	0.93 (2)
P1—C8	1.787 (2)	C8—H8B	0.95 (2)
O2—C8	1.413 (2)	C1—H1A	0.96 (2)
O2—C7	1.424 (2)	O5—C10	1.179 (3)
N4—C5	1.314 (2)	C9—H9B	1.04 (3)
N4—C3	1.383 (2)	C9—H9A	0.99 (3)
N5—C5	1.354 (2)	C11—C12	1.504 (4)
N5—C4	1.3707 (19)	C11—C10	1.508 (3)
N5—C6	1.464 (2)	C11—C13	1.518 (4)
O10—C21	1.309 (2)	C11—C14	1.538 (4)
O10—H10	0.84 (3)	C15—H15B	0.96 (2)
N1—C2	1.328 (2)	C15—H15A	1.05 (2)
N1—H1C	0.81 (2)	O8—C16	1.186 (3)
N1—H1B	0.79 (2)	C16—C17	1.501 (3)
O6—C15	1.413 (2)	C18—C17	1.490 (4)
O3—C9	1.415 (2)	C18—H18A	0.9600
C3—C4	1.383 (2)	C18—H18B	0.9600
C3—C2	1.411 (2)	C18—H18C	0.9600
N2—C1	1.337 (2)	C14—H14A	0.9600
N2—C2	1.341 (2)	C14—H14B	0.9600
N3—C1	1.327 (2)	C14—H14C	0.9600
N3—C4	1.338 (2)	C12—H12A	0.9600
O4—C10	1.337 (2)	C12—H12B	0.9600
O4—C9	1.411 (2)	C12—H12C	0.9600
O7—C16	1.349 (3)	C17—C19	1.471 (5)
O7—C15	1.420 (3)	C17—C20	1.539 (5)
C5—H5	0.990 (19)	C20—H20A	0.9600
C6—C7	1.497 (3)	C20—H20B	0.9600
C6—H6A	0.90 (2)	C20—H20C	0.9600
C6—H6B	0.93 (2)	C19—H19A	0.9600
C7—H7A	1.012 (19)	C19—H19B	0.9600
C7—H7B	1.02 (2)	C19—H19C	0.9600
C22—C21	1.490 (2)	C13—H13A	0.9600
C22—C22ⁱ	1.507 (3)	C13—H13B	0.9600
C22—H22A	0.93 (3)	C13—H13C	0.9600

O1—P1—O3	113.85 (8)	O3—C9—H9B	104.5 (16)
O1—P1—O6	117.52 (7)	O4—C9—H9A	103.8 (15)
O3—P1—O6	101.92 (8)	O3—C9—H9A	108.4 (14)
O1—P1—C8	116.19 (10)	H9B—C9—H9A	120 (2)
O3—P1—C8	106.95 (9)	C12—C11—C10	109.1 (2)
O6—P1—C8	98.37 (8)	C12—C11—C13	112.7 (3)
C8—O2—C7	111.57 (13)	C10—C11—C13	108.6 (2)
C5—N4—C3	104.30 (13)	C12—C11—C14	109.0 (3)
C5—N5—C4	105.98 (13)	C10—C11—C14	110.11 (19)
C5—N5—C6	129.31 (15)	C13—C11—C14	107.4 (2)
C4—N5—C6	124.70 (15)	O6—C15—O7	109.46 (17)
C21—O10—H10	106.4 (17)	O6—C15—H15B	111.4 (14)
C2—N1—H1C	118.2 (13)	O7—C15—H15B	106.6 (14)
C2—N1—H1B	121.6 (14)	O6—C15—H15A	108.1 (13)
H1C—N1—H1B	119.5 (19)	O7—C15—H15A	103.0 (13)
C15—O6—P1	124.52 (15)	H15B—C15—H15A	117.8 (18)
C9—O3—P1	122.53 (14)	O8—C16—O7	121.8 (2)
C4—C3—N4	109.79 (13)	O8—C16—C17	125.3 (2)
C4—C3—C2	116.20 (15)	O7—C16—C17	112.77 (19)
N4—C3—C2	134.00 (15)	O5—C10—O4	121.8 (2)
C1—N2—C2	118.43 (15)	O5—C10—C11	125.9 (2)
C1—N3—C4	110.16 (15)	O4—C10—C11	112.3 (2)
N3—C4—N5	126.26 (14)	C17—C18—H18A	109.5
N3—C4—C3	127.50 (14)	C17—C18—H18B	109.5
N5—C4—C3	106.24 (14)	H18A—C18—H18B	109.5
C10—O4—C9	117.94 (19)	C17—C18—H18C	109.5
C16—O7—C15	117.27 (18)	H18A—C18—H18C	109.5
N4—C5—N5	113.69 (15)	H18B—C18—H18C	109.5
N4—C5—H5	125.8 (11)	C11—C14—H14A	109.5
N5—C5—H5	120.5 (11)	C11—C14—H14B	109.5
N1—C2—N2	118.11 (15)	H14A—C14—H14B	109.5
N1—C2—C3	123.89 (16)	C11—C14—H14C	109.5
N2—C2—C3	118.00 (14)	H14A—C14—H14C	109.5
N5—C6—C7	113.36 (15)	H14B—C14—H14C	109.5
N5—C6—H6A	106.7 (12)	C11—C12—H12A	109.5
C7—C6—H6A	108.1 (12)	C11—C12—H12B	109.5
N5—C6—H6B	104.9 (12)	H12A—C12—H12B	109.5
C7—C6—H6B	110.5 (12)	C11—C12—H12C	109.5
H6A—C6—H6B	113.5 (17)	H12A—C12—H12C	109.5
O2—C7—C6	108.72 (15)	H12B—C12—H12C	109.5
O2—C7—H7A	108.3 (11)	C19—C17—C18	114.6 (3)
C6—C7—H7A	110.1 (10)	C19—C17—C16	110.5 (3)
O2—C7—H7B	105.4 (11)	C18—C17—C16	112.3 (2)
C6—C7—H7B	107.8 (11)	C19—C17—C20	108.7 (4)
H7A—C7—H7B	116.2 (15)	C18—C17—C20	104.0 (4)
C21—C22—C22ⁱ	113.30 (19)	C16—C17—C20	106.1 (3)
C21—C22—H22A	106.6 (15)	C17—C20—H20A	109.5
C22ⁱ—C22—H22A	111.2 (15)	C17—C20—H20B	109.5
C21—C22—H22B	107.6 (12)	H20A—C20—H20B	109.5
C22ⁱ—C22—H22B	109.4 (12)	C17—C20—H20C	109.5
H22A—C22—H22B	108.6 (18)	H20A—C20—H20C	109.5
O9—C21—O10	122.58 (16)	H20B—C20—H20C	109.5
O9—C21—C22	123.77 (16)	C17—C19—H19A	109.5
O10—C21—C22	113.65 (15)	C17—C19—H19B	109.5
O2—C8—P1	108.92 (13)	H19A—C19—H19B	109.5
O2—C8—H8A	112.5 (14)	C17—C19—H19C	109.5
P1—C8—H8A	111.6 (15)	H19A—C19—H19C	109.5
O2—C8—H8B	111.4 (14)	H19B—C19—H19C	109.5
P1—C8—H8B	109.8 (14)	C11—C13—H13A	109.5
H8A—C8—H8B	102.5 (19)	C11—C13—H13B	109.5
N3—C1—N2	129.67 (18)	H13A—C13—H13B	109.5
N3—C1—H1A	115.2 (12)	C11—C13—H13C	109.5
N2—C1—H1A	115.1 (12)	H13A—C13—H13C	109.5
O4—C9—O3	107.72 (17)	H13B—C13—H13C	109.5
O4—C9—H9B	111.6 (16)

Symmetry code: (i) −x+2, −y−1, −z.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1C···O1ⁱⁱ	0.812 (19)	2.14 (2)	2.941 (2)	170.16 (18)
N1—H1B···O9	0.79 (2)	2.05 (2)	2.842 (2)	175 (2)
O10—H10···N4	0.84 (2)	1.91 (2)	2.734 (2)	166 (2)

Symmetry code: (ii) x+1, y−1, z.

Experimental details

Crystal data
Chemical formula	C₂₀H₃₂N₅O₈P·0.5C₄H₆O₄
M_r	560.52
Crystal system, space group	Triclinic, P1
Temperature (K)	296
a, b, c (Å)	7.7122 (12), 10.1577 (15), 19.185 (3)
α, β, γ (°)	80.409 (8), 79.718 (9), 80.407 (8)
V (Å³)	1443.5 (4)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.15
Crystal size (mm)	0.11 × 0.10 × 0.08

Data collection
Diffractometer	Bruker SMART CCD diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2002)
T_min, T_max	0.982, 0.987
No. of measured, independent and observed [I > 2σ(I)] reflections	49737, 7222, 4593
R_int	0.053
(sin θ/λ)_max (Å⁻¹)	0.669

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.046, 0.143, 1.01
No. of reflections	7222
No. of parameters	417
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.38, −0.29

Computer programs: SMART (Bruker, 2002), SAINT (Bruker, 2002), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997), WinGX (Farrugia, 1999).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1C···O1ⁱ	0.812 (19)	2.14 (2)	2.941 (2)	170.16 (18)
N1—H1B···O9	0.79 (2)	2.05 (2)	2.842 (2)	175 (2)
O10—H10···N4	0.84 (2)	1.91 (2)	2.734 (2)	166 (2)

Symmetry code: (i) x+1, y−1, z.

Acknowledgements

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (grant No. 2010-0005045). It was also supported by the Advanced Track of Green Production Processing for Reducing Greenhouse Gas Emissions of the Korea Institute of Energy Technology Evaluation and Planning (KETEP) funded by the Korean Government Ministry of Knowledge Economy (grant No. 20114010203140).

References

Bruker (2002). SADABS, SAINT and SMART. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Chang, Y., Zheng, Q.-T. & Lu, Y. (2007). Acta Cryst. E63, o1014–o1015. Web of Science CSD CrossRef IUCr Journals Google Scholar
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565. CrossRef IUCr Journals Google Scholar
Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838. CrossRef CAS IUCr Journals Google Scholar
Julander, J. G., Sidwell, R. W. & Morrey, J. D. (2002). Antiviral Res. 55, 27–40. Web of Science CrossRef PubMed CAS Google Scholar
Qaqish, R. B., Mattes, K. A. & Ritchie, D. J. (2003). Clin. Ther. 25, 3084–3099. Web of Science CrossRef PubMed CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Starrett, J. E., Tortolani, D. R., Hitchcock, M. J. M., Martin, J. C. & Mansuri, M. M. (1992). Antiviral Res. 19, 267–273. CrossRef PubMed CAS Web of Science Google Scholar
Yu, R. H., Schultze, J. C., Rohloff, J. C., Dudzinski, P. W. & Kelly, D. E. (1999). Org. Process Res. Dev. 3, 53–55. Web of Science CrossRef CAS Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 68| Part 3| March 2012| Pages o809-o810

doi:10.1107/S1600536812006873

Open

access

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Plain Text

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Plain Text

Search IUCr Journals		doi		Advanced search
Author		volume	page

organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Bis[(2,2-di­methyl­propano­yl­oxy)meth­yl] {[2-(6-amino-9H-purin-9-yl)eth­­oxy]meth­yl}phospho­nate–succinic acid (2/1)

Related literature

Experimental

Crystal data

Data collection

Refinement

Supporting information

Acknowledgements

References

organic compounds

Bis[(2,2-dimethylpropanoyloxy)methyl] {[2-(6-amino-9H-purin-9-yl)ethoxy]methyl}phosphonate–succinic acid (2/1)