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ISSN: 2056-9890

Crystal structures of 2-[(4,6-di­amino­pyrimidin-2-yl)sulfan­yl]-N-(3-nitro­phen­yl)acetamide monohydrate and N-(2-chloro­phen­yl)-2-[(4,6-di­amino­pyrimidin-2-yl)sulfan­yl]acetamide

CROSSMARK_Color_square_no_text.svg

aCentre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600 025, India, and bDepartment of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi, India
*Correspondence e-mail: shirai2011@gmail.com

Edited by H. Stoeckli-Evans, University of Neuchâtel, Switzerland (Received 1 July 2016; accepted 18 July 2016; online 22 July 2016)

The title compounds, C12H12N6O3S·H2O, (I), and C12H12ClN5OS, (II), are 2-[(4,6-di­amino­pyrimidin-2-yl)sulfan­yl]acetamides. Compound (I) crystallized as a monohydrate. In both compounds, the mol­ecules have a folded conformation, with the pyrimidine ring being inclined to the benzene ring by 56.18 (6)° in (I) and by 67.84 (6)° in (II). In both mol­ecules, there is an intra­molecular N—H⋯N hydrogen bond stabilizing the folded conformation. In (I), there is also a C—H⋯O intra­molecular short contact, and in (II) an intra­molecular N—H⋯Cl hydrogen bond is present. In the crystal of (I), mol­ecules are linked by a series of N—H⋯O, O—H⋯O and O—H⋯N hydrogen bonds, forming undulating sheets parallel to the (100). The sheets are linked via an N—H⋯Owater hydrogen bond, forming a three-dimensional network. In the crystal of (II), mol­ecules are linked by a series of N—H⋯O, N—H⋯N and C—H⋯O hydrogen bonds, forming slabs parallel to (001).

1. Chemical context

Recent studies have shown that di­amino substituted pyrimidines are active inhibitors of human di­hydro­folate reductase (hDHFR) and also possess inhibitory potency against tyrosine kinase (Gangjee et al., 2006[Gangjee, A., Yang, J., McGuire, J. J. & Kisliuk, R. L. (2006). Bioorg. Med. Chem. 14, 8590-8598.]). 2,4-di­amino pyrimidine derivatives have anti-retro viral activity (Hocková et al., 2004[Hocková, D., Holý, A. N., Masojídková, M., Andrei, G., Snoeck, R., De Clercq, E. & Balzarini, J. (2004). Bioorg. Med. Chem. 12, 3197-3202.]) and also anti-trypanosoma brucei activity (Perales et al., 2011[Perales, J. B., Freeman, J., Bacchi, C. J., Bowling, T., Don, R., Gaukel, E., Mercer, L., Moore, J. A. III, Nare, B., Nguyen, T. M., Noe, R. A., Randolph, R., Rewerts, C., Wring, S. A., Yarlett, N. & Jacobs, R. T. (2011). Bioorg. Med. Chem. Lett. 21, 2816-2819.]). A series of 2,4-di­amino­pyrimidines have as also been prepared to study their immuno-suppressant activity (Blumenkopf et al., 2003[Blumenkopf, T. A., Mueller, E. E. & Roskamp, E. J. (2003). Patent US20030191307A1.]). Pyrimidines are also potent anti­viral agents and a series of N-benzyl-2-(4,6-di­amino­pyrimidin-2-ylsulfan­yl)acetamides have been designed to fight Dengue Virus Protease (Timiri et al., 2016[Timiri, A. K., Sinha, B. N. & Jayaprakash, V. (2016). Eur. J. Med. Chem. 117, 125-143.]). A series 5-substituted benzyl-2,4-di­amino pyrimidine derivatives have also been synthesized as c-Fms kinase inhibitors (Xu et al., 2010[Xu, L.-B., Sun, W., Liu, H.-Y., Wang, L.-L., Xiao, J.-H., Yang, X.-H. & Li, S. (2010). Chin. Chem. Lett. 21, 1318-1321.]). As part of our studies in this area, we now describe the syntheses and crystal structures of the title compounds.

2. Structural commentary

The mol­ecular structures of compounds (I)[link] and (II)[link] are illus­trated in Figs. 1[link] and 2[link], respectively. In compound (I)[link], the pyrimidine ring makes a dihedral angle of 56.18 (6)° with the benzene ring (C7–C12). The nitro group is inclined by 16.3 (3)° to the benzene ring to which it is attached. The amine nitro­gen atoms, N1 and N2, are displaced from the pyrimidine ring by 0.028 (2) and 0.026 (2) Å, respectively.

[Scheme 1]
[Figure 1]
Figure 1
The mol­ecular structure of compound (I)[link], with atom labelling. Displacement ellipsoids are drawn at the 50% probability level. Intra­molecular hydrogen bonds are shown as dashed lines (see Table 1[link]).
[Figure 2]
Figure 2
The mol­ecular structure of compound (II)[link], with atom labelling. Displacement ellipsoids are drawn at the 50% probability level. Intra­molecular hydrogen bonds are shown as dashed lines (see Table 2[link]).

In compound (II)[link], the pyrimidine ring makes a dihedral angle of 67.84 (6)° with the chloro­benzene ring (C7–C12). The amine nitro­gen atoms, N1 and N2, are displaced from the pyrimidine ring by 0.009 (2) and 0.030 (2) Å, respectively. The chlorine atom, Cl1, attached to the benzene ring deviates by 0.053 (1) Å from the ring plane.

In both the compounds, the folded conformation is reinforced by an intra­molecular N—H⋯O hydrogen bond [Fig. 1[link], Table 1[link] for (I)[link] and Fig. 2[link], Table 2[link] for (II)]. In (I)[link] there is an intra­molecular C—H⋯O contact (Table 1[link] and Fig. 1[link]) and in (II)[link] an intra­molecular N—H⋯Cl hydrogen bond is also present (Table 2[link] and Fig. 2[link]).

Table 1
Hydrogen-bond geometry (Å, °) for (I)[link]

D—H⋯A D—H H⋯A DA D—H⋯A
N5—H5⋯N4 0.86 (3) 2.05 (3) 2.832 (3) 151 (3)
C12—H12⋯O1 0.93 2.35 2.911 (3) 118
N1—H1A⋯O1Wi 0.83 (3) 2.16 (3) 2.979 (3) 170 (2)
N1—H1B⋯O2ii 0.84 (3) 2.29 (3) 3.082 (3) 159 (3)
N2—H2A⋯O3iii 0.80 (3) 2.58 (3) 3.255 (3) 143 (3)
N2—H2B⋯O1ii 0.83 (3) 2.09 (3) 2.904 (3) 170 (3)
O1W—H1WA⋯N3iv 0.86 2.09 2.919 (3) 162
O1W—H1WB⋯O3v 0.90 2.64 3.294 (3) 130
Symmetry codes: (i) x-1, y, z; (ii) [-x+{\script{1\over 2}}, y+{\script{1\over 2}}, z+{\script{1\over 2}}]; (iii) x, y, z+1; (iv) [-x+1, -y+1, z-{\script{1\over 2}}]; (v) [-x+1, -y+1, z+{\script{1\over 2}}].

Table 2
Hydrogen-bond geometry (Å, °) for (II)[link]

D—H⋯A D—H H⋯A DA D—H⋯A
N5—H5⋯N4 0.85 (2) 2.12 (2) 2.898 (2) 152 (2)
N2—H2A⋯Cl1 0.81 (3) 2.81 (2) 3.493 (2) 143 (2)
N1—H1A⋯N3i 0.85 (2) 2.21 (2) 3.058 (2) 174 (2)
N1—H1B⋯O1ii 0.83 (2) 2.21 (2) 2.992 (2) 157 (2)
N2—H2A⋯O1iii 0.81 (3) 2.56 (2) 3.095 (2) 124 (2)
C2—H2⋯O1ii 0.93 2.64 3.353 (2) 134
Symmetry codes: (i) -x, -y, -z+1; (ii) x-1, y-1, z; (iii) x-1, y, z.

3. Supra­molecular features

In the crystal of compound (I)[link], mol­ecules are linked by a series of N—H⋯O, O—H⋯O and O—H⋯N hydrogen bonds, forming undulating sheets parallel to the bc plane (Table 1[link] and Fig. 3[link]). The sheets are linked via an N—H⋯Owater hydrogen bond, forming a three-dimensional network (Table 1[link] and Fig. 3[link]). Through pairs of N—H⋯O hydrogen bonds, R22(15) and R44(29) ring motifs are generated (Table 1[link] and Fig. 4[link]).

[Figure 3]
Figure 3
The crystal packing of compound (I)[link], viewed along the b axis. Hydrogen bonds are shown as dashed lines (see Table 1[link]). C-bound H atoms have been excluded for clarity.
[Figure 4]
Figure 4
A view of the hydrogen-bonded ring motifs in the crystal of compound (I)[link]. Details of the hydrogen bonding are given in Table 1[link].

In the crystal of compound (II)[link], mol­ecules are linked by a series of N—H⋯O, N—H⋯N and C—H⋯O hydrogen bonds, forming slabs parallel to the ab plane (Table 2[link] and Fig. 5[link]). Through pairs of N—H⋯N hydrogen bonds, R22(8) ring motifs are generated, and through further pairs of N—H⋯N and N—H⋯O hydrogen bonds R44(18) ring motifs are also formed (Table 2[link] and Fig. 6[link]).

[Figure 5]
Figure 5
The crystal packing of compound (II)[link], viewed along the a axis. Hydrogen bonds are shown as dashed lines (see Table 2[link])·C-bound H atoms have been excluded for clarity.
[Figure 6]
Figure 6
A view of the hydrogen-bonded ring motifs in the crystal of compound (II)[link]. Details of the hydrogen bonding are given in Table 2[link].

4. Database survey

A search of the Cambridge Structural Database (Version 5.37, update May 2016; Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]) for 2-(pyrimidin-2-ylsulfan­yl)-N-phenyl­acetamides yielded only three hits. There are two 4,6-di­methyl­pyrimidine analogues viz. 2-(4,6-di­meth­yl­pyrimidin-2-ylsulfan­yl)-N-phenyl­acetamide (DIWXAJ; Gao et al., 2008[Gao, L.-X., Fang, G.-J., Feng, J.-G., Liang, D. & Wang, W. (2008). Acta Cryst. E64, o760.]) and N-(2-chloro­phen­yl)-2-(4,6-di­methyl­pyrimidin-2-ylsulfan­yl)acetamide QOTQEW; Li et al., 2009[Li, Q., Wang, W., Wang, H., Gao, Y. & Qiu, H. (2009). Acta Cryst. E65, o959.]), but only one 4,6-di­amino­pyrimidine compound viz. 2-[(4,6-diamino­pyrimidin-2-yl)sulfan­yl]-N-(2-methyl­phen­yl)acetamide (GOKWIO; Subasri et al., 2014[Subasri, S., Kumar, T. A., Sinha, B. N., Jayaprakash, V. & Velmurugan, D. (2014). Acta Cryst. E70, o850.]). In the 4,6-di­methyl­pyrimidine analogues, DIWXAJ and QOTQEW, the pyrimidine ring is inclined to the benzene ring by 88.86 (15) and 79.60 (8)°, respectively. In the 4,6-di­amino­pyrimidine compound, GOKWIO, the two rings are inclined to one another by 54.73 (9)°. This last value is similar to that observed in the compound (I)[link], viz. 56.18 (6)°.

5. Synthesis and crystallization

Compound (I): To a solution of 4,6-di­amino-pyrimidine-2-thiol (0.5 g; 3.52 mmol) in 25 ml of ethanol in a round-bottom flask, potassium hydroxide (0.2 g; 3.52 mmol) was added and the mixture was refluxed for half an hour and to it 3.52 mmol of 3-nitro phenyl­acetamide was added and refluxed for 4 h. At the end of the reaction (observed by TLC), ethanol was evaporated under vacuum and cold water was added and the precipitate filtered and dried to give compound (I)[link] as a crystalline powder (yield 88–96%). After purification, the compound was recrystallized from ethyl acetate solution by slow evaporation of the solvent.

Compound (II): To a solution of 4,6-di­amino-pyrimidine-2-thiol (0.5 g; 3.52 mmol) in 25 ml of ethanol in a round-bottom flask potassium hydroxide (0.2 g; 3.52 mmol) was added and refluxed for half an hour and to it 3.52 mmol of 2-chloro-phenyl­acetamide was added and the mixture was refluxed for 3 h. At the end of the reaction (observed by TLC), ethanol was evaporated under vacuum and cold water was added, and the precipitate was filtered and dried to give compound (II)[link] as a crystalline powder (yield 88–96%). After purification, the compound was recrystallized from ethanol solution by slow evaporation of the solvent.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3[link]. For both compounds, the NH2 and NH H atoms, and the water H atoms for (I)[link], were located in difference Fourier maps. The N-bound H atoms were freely refined, while the water H atoms were initially freely refined and in the final cycles of refinement as riding atoms. The C-bound H atoms were placed in calculated positions and refined as riding: C—H = 0.93–0.97 Å with Uiso(H) = 1.2Ueq(C).

Table 3
Experimental details

  (I) (II)
Crystal data
Chemical formula C12H12N6O3S·H2O C12H12ClN5OS
Mr 338.35 309.78
Crystal system, space group Orthorhombic, Pna21 Triclinic, P[\overline{1}]
Temperature (K) 293 293
a, b, c (Å) 7.2326 (1), 14.3442 (2), 14.0940 (3) 7.2528 (2), 7.6249 (3), 13.0649 (4)
α, β, γ (°) 90, 90, 90 91.410 (2), 105.924 (2), 94.647 (2)
V3) 1462.19 (4) 691.68 (4)
Z 4 2
Radiation type Mo Kα Mo Kα
μ (mm−1) 0.25 0.43
Crystal size (mm) 0.30 × 0.25 × 0.20 0.30 × 0.20 × 0.15
 
Data collection
Diffractometer Bruker SMART APEXII area-detector Bruker SMART APEXII area-detector
Absorption correction Multi-scan (SADABS; Bruker, 2008[Bruker (2008). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Multi-scan (SADABS; Bruker, 2008[Bruker (2008). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.785, 0.845 0.785, 0.845
No. of measured, independent and observed [I > 2σ(I)] reflections 7912, 3265, 3034 10154, 2822, 2519
Rint 0.021 0.022
(sin θ/λ)max−1) 0.667 0.626
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.027, 0.069, 1.04 0.035, 0.099, 1.04
No. of reflections 3265 2822
No. of parameters 229 201
No. of restraints 1 0
H-atom treatment H atoms treated by a mixture of independent and constrained refinement H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.16, −0.17 0.50, −0.50
Absolute structure Flack x determined using 1217 quotients [(I+)−(I)]/[(I+)+(I)] (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.])
Absolute structure parameter 0.07 (3)
Computer programs: APEX2 (Bruker, 2008[Bruker (2008). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), SAINT (Bruker, 2008[Bruker (2008). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), Mercury (Macrae et al., 2008[Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466-470.]) and PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]), SHELXL2014 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]) and PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]).

Supporting information


Computing details top

For both compounds, data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: Mercury (Macrae et al., 2008) and PLATON (Spek, 2009); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015) and PLATON (Spek, 2009).

(I) 2-[(4,6-Diaminopyrimidin-2-yl)sulfanyl]-N-(3-nitrophenyl)acetamide monohydrate top
Crystal data top
C12H12N6O3S·H2ODx = 1.537 Mg m3
Mr = 338.35Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pna21Cell parameters from 3265 reflections
a = 7.2326 (1) Åθ = 2.0–28.3°
b = 14.3442 (2) ŵ = 0.25 mm1
c = 14.0940 (3) ÅT = 293 K
V = 1462.19 (4) Å3Block, colourless
Z = 40.30 × 0.25 × 0.20 mm
F(000) = 704
Data collection top
Bruker SMART APEXII area-detector
diffractometer
3034 reflections with I > 2σ(I)
ω and φ scansRint = 0.021
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
θmax = 28.3°, θmin = 2.0°
Tmin = 0.785, Tmax = 0.845h = 59
7912 measured reflectionsk = 1819
3265 independent reflectionsl = 1518
Refinement top
Refinement on F2Hydrogen site location: mixed
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.027 w = 1/[σ2(Fo2) + (0.0396P)2 + 0.1263P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.069(Δ/σ)max = 0.001
S = 1.04Δρmax = 0.16 e Å3
3265 reflectionsΔρmin = 0.17 e Å3
229 parametersExtinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
1 restraintExtinction coefficient: 0.0039 (10)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack x determined using 1217 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
Secondary atom site location: difference Fourier mapAbsolute structure parameter: 0.07 (3)
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
S10.12955 (8)0.37215 (3)0.66439 (4)0.03810 (14)
O10.2112 (3)0.32497 (11)0.42274 (13)0.0555 (5)
O20.4515 (3)0.40381 (12)0.13791 (14)0.0570 (5)
O30.4586 (3)0.53670 (14)0.06709 (14)0.0602 (5)
N10.0426 (3)0.69929 (14)0.58998 (15)0.0483 (5)
H1A0.112 (3)0.6759 (19)0.550 (2)0.039 (7)*
H1B0.049 (4)0.7564 (18)0.601 (2)0.048 (7)*
N20.2912 (3)0.62828 (15)0.87403 (16)0.0473 (5)
H2A0.343 (4)0.587 (2)0.902 (2)0.052 (9)*
H2B0.303 (4)0.683 (2)0.891 (2)0.058 (8)*
N30.2016 (2)0.51355 (12)0.77054 (12)0.0346 (4)
N40.0368 (2)0.54948 (11)0.62840 (12)0.0327 (4)
N50.1324 (3)0.47612 (12)0.44843 (13)0.0361 (4)
H50.081 (4)0.5115 (19)0.490 (2)0.050 (7)*
N60.4308 (3)0.48792 (13)0.13678 (13)0.0404 (4)
C10.0378 (3)0.64158 (12)0.65303 (16)0.0351 (4)
C20.1209 (3)0.67214 (15)0.73550 (15)0.0386 (5)
H20.12060.73490.75220.046*
C30.2048 (3)0.60567 (14)0.79264 (17)0.0359 (4)
C40.1191 (3)0.49297 (13)0.68900 (14)0.0318 (4)
C50.0093 (3)0.36034 (14)0.55277 (16)0.0369 (5)
H5A0.03450.29670.54660.044*
H5B0.09790.40100.55320.044*
C60.1278 (3)0.38380 (14)0.46763 (15)0.0350 (4)
C70.2255 (3)0.52300 (13)0.37571 (15)0.0327 (4)
C80.2440 (4)0.61934 (14)0.38488 (18)0.0418 (5)
H80.20210.64880.43960.050*
C90.3239 (4)0.67138 (15)0.31366 (19)0.0471 (6)
H90.33680.73550.32110.057*
C100.3850 (3)0.62925 (15)0.23135 (18)0.0418 (5)
H100.43640.66400.18230.050*
C110.3670 (3)0.53390 (15)0.22449 (15)0.0339 (4)
C120.2907 (3)0.47907 (13)0.29473 (15)0.0331 (4)
H120.28320.41470.28800.040*
O1W0.7494 (3)0.61566 (15)0.42859 (15)0.0615 (5)
H1WA0.76370.58850.37480.092*
H1WB0.63770.60030.45210.092*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0581 (3)0.0259 (2)0.0302 (2)0.00098 (19)0.0040 (2)0.0025 (2)
O10.0851 (13)0.0319 (8)0.0494 (11)0.0075 (8)0.0205 (9)0.0010 (7)
O20.0763 (12)0.0476 (9)0.0470 (11)0.0082 (9)0.0072 (9)0.0122 (8)
O30.0765 (12)0.0711 (12)0.0328 (9)0.0071 (10)0.0107 (9)0.0022 (9)
N10.0692 (15)0.0309 (9)0.0448 (12)0.0072 (9)0.0120 (11)0.0024 (8)
N20.0644 (14)0.0385 (11)0.0390 (12)0.0024 (10)0.0091 (10)0.0079 (9)
N30.0424 (9)0.0331 (8)0.0283 (9)0.0021 (7)0.0003 (7)0.0017 (7)
N40.0427 (9)0.0278 (7)0.0278 (8)0.0008 (7)0.0018 (7)0.0007 (6)
N50.0507 (11)0.0288 (8)0.0287 (9)0.0018 (7)0.0073 (8)0.0020 (7)
N60.0394 (9)0.0484 (10)0.0336 (10)0.0015 (8)0.0007 (8)0.0030 (8)
C10.0408 (10)0.0297 (8)0.0349 (11)0.0008 (7)0.0066 (9)0.0008 (8)
C20.0517 (13)0.0281 (9)0.0360 (11)0.0036 (9)0.0036 (10)0.0058 (8)
C30.0396 (10)0.0362 (9)0.0320 (11)0.0049 (9)0.0062 (8)0.0038 (8)
C40.0378 (10)0.0285 (9)0.0290 (11)0.0033 (8)0.0059 (8)0.0007 (7)
C50.0467 (11)0.0319 (10)0.0322 (11)0.0077 (8)0.0008 (9)0.0009 (8)
C60.0446 (12)0.0303 (9)0.0302 (11)0.0013 (8)0.0024 (9)0.0007 (7)
C70.0395 (11)0.0295 (9)0.0292 (10)0.0005 (8)0.0003 (8)0.0008 (8)
C80.0561 (13)0.0317 (10)0.0376 (12)0.0005 (9)0.0074 (10)0.0035 (9)
C90.0664 (15)0.0280 (9)0.0469 (13)0.0015 (10)0.0084 (12)0.0025 (9)
C100.0500 (13)0.0350 (11)0.0404 (13)0.0008 (9)0.0078 (11)0.0076 (9)
C110.0360 (10)0.0369 (10)0.0288 (10)0.0026 (9)0.0001 (8)0.0002 (8)
C120.0380 (10)0.0301 (8)0.0311 (10)0.0006 (8)0.0011 (8)0.0003 (8)
O1W0.0706 (12)0.0695 (12)0.0444 (11)0.0050 (9)0.0003 (10)0.0118 (9)
Geometric parameters (Å, º) top
S1—C41.769 (2)C1—C21.380 (3)
S1—C51.805 (2)C2—C31.388 (3)
O1—C61.215 (3)C2—H20.9300
O2—N61.216 (2)C5—C61.512 (3)
O3—N61.223 (3)C5—H5A0.9700
N1—C11.347 (3)C5—H5B0.9700
N1—H1A0.83 (3)C7—C121.386 (3)
N1—H1B0.84 (3)C7—C81.394 (3)
N2—C31.346 (3)C8—C91.378 (3)
N2—H2A0.80 (3)C8—H80.9300
N2—H2B0.83 (3)C9—C101.381 (3)
N3—C41.328 (3)C9—H90.9300
N3—C31.358 (3)C10—C111.377 (3)
N4—C41.319 (3)C10—H100.9300
N4—C11.366 (2)C11—C121.380 (3)
N5—C61.352 (3)C12—H120.9300
N5—C71.398 (3)O1W—H1WA0.8582
N5—H50.86 (3)O1W—H1WB0.9004
N6—C111.475 (3)
C4—S1—C5104.01 (9)C6—C5—H5A108.9
C1—N1—H1A117.8 (18)S1—C5—H5A108.9
C1—N1—H1B120 (2)C6—C5—H5B108.9
H1A—N1—H1B120 (3)S1—C5—H5B108.9
C3—N2—H2A117 (2)H5A—C5—H5B107.7
C3—N2—H2B121 (2)O1—C6—N5124.3 (2)
H2A—N2—H2B121 (3)O1—C6—C5122.68 (19)
C4—N3—C3114.97 (18)N5—C6—C5113.01 (18)
C4—N4—C1115.30 (18)C12—C7—C8119.6 (2)
C6—N5—C7129.02 (18)C12—C7—N5123.27 (17)
C6—N5—H5115.5 (19)C8—C7—N5117.05 (19)
C7—N5—H5115.1 (19)C9—C8—C7120.6 (2)
O2—N6—O3123.9 (2)C9—C8—H8119.7
O2—N6—C11118.11 (18)C7—C8—H8119.7
O3—N6—C11117.96 (18)C8—C9—C10120.6 (2)
N1—C1—N4115.1 (2)C8—C9—H9119.7
N1—C1—C2123.28 (19)C10—C9—H9119.7
N4—C1—C2121.57 (19)C11—C10—C9117.6 (2)
C1—C2—C3117.44 (19)C11—C10—H10121.2
C1—C2—H2121.3C9—C10—H10121.2
C3—C2—H2121.3C10—C11—C12123.6 (2)
N2—C3—N3116.0 (2)C10—C11—N6118.26 (19)
N2—C3—C2122.1 (2)C12—C11—N6118.14 (18)
N3—C3—C2121.9 (2)C11—C12—C7117.89 (17)
N4—C4—N3128.79 (18)C11—C12—H12121.1
N4—C4—S1119.62 (15)C7—C12—H12121.1
N3—C4—S1111.59 (15)H1WA—O1W—H1WB108.8
C6—C5—S1113.43 (15)
C4—N4—C1—N1178.57 (19)S1—C5—C6—N584.2 (2)
C4—N4—C1—C20.5 (3)C6—N5—C7—C1218.1 (3)
N1—C1—C2—C3177.6 (2)C6—N5—C7—C8164.9 (2)
N4—C1—C2—C30.3 (3)C12—C7—C8—C91.0 (4)
C4—N3—C3—N2178.7 (2)N5—C7—C8—C9176.0 (2)
C4—N3—C3—C22.5 (3)C7—C8—C9—C100.8 (4)
C1—C2—C3—N2179.3 (2)C8—C9—C10—C111.5 (4)
C1—C2—C3—N31.9 (3)C9—C10—C11—C120.5 (3)
C1—N4—C4—N30.3 (3)C9—C10—C11—N6179.7 (2)
C1—N4—C4—S1179.23 (14)O2—N6—C11—C10164.8 (2)
C3—N3—C4—N41.7 (3)O3—N6—C11—C1015.6 (3)
C3—N3—C4—S1177.82 (16)O2—N6—C11—C1215.9 (3)
C5—S1—C4—N40.85 (19)O3—N6—C11—C12163.6 (2)
C5—S1—C4—N3179.56 (14)C10—C11—C12—C71.3 (3)
C4—S1—C5—C681.31 (16)N6—C11—C12—C7177.94 (17)
C7—N5—C6—O11.4 (4)C8—C7—C12—C112.0 (3)
C7—N5—C6—C5179.6 (2)N5—C7—C12—C11174.86 (19)
S1—C5—C6—O194.8 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N5—H5···N40.86 (3)2.05 (3)2.832 (3)151 (3)
C12—H12···O10.932.352.911 (3)118
N1—H1A···O1Wi0.83 (3)2.16 (3)2.979 (3)170 (2)
N1—H1B···O2ii0.84 (3)2.29 (3)3.082 (3)159 (3)
N2—H2A···O3iii0.80 (3)2.58 (3)3.255 (3)143 (3)
N2—H2B···O1ii0.83 (3)2.09 (3)2.904 (3)170 (3)
O1W—H1WA···N3iv0.862.092.919 (3)162
O1W—H1WB···O3v0.902.643.294 (3)130
Symmetry codes: (i) x1, y, z; (ii) x+1/2, y+1/2, z+1/2; (iii) x, y, z+1; (iv) x+1, y+1, z1/2; (v) x+1, y+1, z+1/2.
(II) N-(2-Chlorophenyl)-2-[(4,6-diaminopyrimidin-2-yl)sulfanyl]acetamide top
Crystal data top
C12H12ClN5OSZ = 2
Mr = 309.78F(000) = 320
Triclinic, P1Dx = 1.487 Mg m3
a = 7.2528 (2) ÅMo Kα radiation, λ = 0.71073 Å
b = 7.6249 (3) ÅCell parameters from 2822 reflections
c = 13.0649 (4) Åθ = 1.6–26.4°
α = 91.410 (2)°µ = 0.43 mm1
β = 105.924 (2)°T = 293 K
γ = 94.647 (2)°Block, colourless
V = 691.68 (4) Å30.30 × 0.20 × 0.15 mm
Data collection top
Bruker SMART APEXII area-detector
diffractometer
2519 reflections with I > 2σ(I)
ω and φ scansRint = 0.022
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
θmax = 26.4°, θmin = 1.6°
Tmin = 0.785, Tmax = 0.845h = 98
10154 measured reflectionsk = 99
2822 independent reflectionsl = 1616
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.035Hydrogen site location: mixed
wR(F2) = 0.099H atoms treated by a mixture of independent and constrained refinement
S = 1.04 w = 1/[σ2(Fo2) + (0.0515P)2 + 0.2692P]
where P = (Fo2 + 2Fc2)/3
2822 reflections(Δ/σ)max < 0.001
201 parametersΔρmax = 0.50 e Å3
0 restraintsΔρmin = 0.50 e Å3
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Cl10.32045 (7)0.83502 (8)0.11080 (5)0.06488 (18)
S10.22688 (6)0.44103 (6)0.41282 (3)0.04714 (15)
O10.35760 (17)0.81194 (17)0.26781 (10)0.0503 (3)
N10.2505 (3)0.0531 (2)0.40354 (14)0.0541 (4)
H1A0.163 (3)0.091 (3)0.4537 (18)0.051 (6)*
H1B0.361 (3)0.101 (3)0.3829 (18)0.058 (6)*
N20.4671 (2)0.4665 (2)0.23211 (16)0.0576 (5)
H2A0.437 (3)0.572 (3)0.2321 (18)0.062 (7)*
H2B0.584 (4)0.428 (3)0.2221 (19)0.070 (7)*
N30.03937 (19)0.19020 (19)0.40540 (10)0.0396 (3)
N40.14840 (18)0.44884 (18)0.31711 (10)0.0371 (3)
N50.0527 (2)0.6847 (2)0.20471 (11)0.0416 (3)
H50.040 (3)0.631 (3)0.2233 (15)0.045 (5)*
C10.2221 (2)0.1113 (2)0.37325 (12)0.0383 (3)
C20.3723 (2)0.1992 (2)0.31353 (13)0.0403 (4)
H20.49700.14470.29100.048*
C30.3310 (2)0.3694 (2)0.28860 (13)0.0378 (3)
C40.0176 (2)0.3525 (2)0.37342 (11)0.0353 (3)
C50.2110 (3)0.6742 (2)0.39173 (13)0.0453 (4)
H5A0.09240.70680.40450.054*
H5B0.31690.73960.44420.054*
C60.2155 (2)0.7302 (2)0.28193 (12)0.0359 (3)
C70.0187 (2)0.7245 (2)0.09613 (12)0.0375 (3)
C80.1521 (2)0.7917 (2)0.04306 (14)0.0428 (4)
C90.1897 (3)0.8314 (3)0.06301 (15)0.0545 (5)
H90.30480.87630.09760.065*
C100.0557 (4)0.8039 (3)0.11667 (15)0.0603 (6)
H100.07950.83120.18790.072*
C110.1148 (3)0.7360 (3)0.06546 (15)0.0556 (5)
H110.20480.71680.10240.067*
C120.1516 (3)0.6965 (2)0.04065 (14)0.0454 (4)
H120.26650.65080.07480.055*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0473 (3)0.0730 (4)0.0803 (4)0.0106 (2)0.0244 (2)0.0255 (3)
S10.0309 (2)0.0609 (3)0.0435 (2)0.00578 (18)0.00128 (17)0.0193 (2)
O10.0404 (6)0.0548 (7)0.0492 (7)0.0158 (5)0.0072 (5)0.0071 (6)
N10.0440 (9)0.0474 (9)0.0579 (10)0.0079 (7)0.0061 (8)0.0187 (7)
N20.0319 (8)0.0501 (10)0.0858 (13)0.0021 (7)0.0066 (8)0.0271 (9)
N30.0339 (7)0.0466 (8)0.0349 (7)0.0005 (6)0.0043 (5)0.0105 (6)
N40.0318 (6)0.0431 (7)0.0360 (7)0.0010 (5)0.0094 (5)0.0082 (5)
N50.0339 (7)0.0515 (8)0.0360 (7)0.0097 (6)0.0072 (6)0.0099 (6)
C10.0388 (8)0.0418 (8)0.0307 (7)0.0015 (7)0.0052 (6)0.0049 (6)
C20.0314 (8)0.0458 (9)0.0390 (8)0.0034 (6)0.0037 (6)0.0068 (7)
C30.0322 (8)0.0447 (9)0.0364 (8)0.0017 (6)0.0097 (6)0.0070 (6)
C40.0315 (7)0.0469 (9)0.0262 (7)0.0018 (6)0.0073 (6)0.0049 (6)
C50.0447 (9)0.0511 (10)0.0343 (8)0.0120 (7)0.0062 (7)0.0025 (7)
C60.0355 (8)0.0324 (7)0.0376 (8)0.0031 (6)0.0082 (6)0.0013 (6)
C70.0398 (8)0.0337 (8)0.0350 (8)0.0089 (6)0.0069 (6)0.0043 (6)
C80.0405 (9)0.0384 (8)0.0446 (9)0.0071 (7)0.0061 (7)0.0053 (7)
C90.0582 (11)0.0472 (10)0.0447 (10)0.0083 (8)0.0049 (8)0.0103 (8)
C100.0873 (15)0.0526 (11)0.0325 (9)0.0121 (10)0.0073 (9)0.0031 (8)
C110.0761 (14)0.0496 (10)0.0447 (10)0.0064 (9)0.0269 (10)0.0024 (8)
C120.0486 (10)0.0421 (9)0.0456 (9)0.0015 (7)0.0145 (8)0.0029 (7)
Geometric parameters (Å, º) top
Cl1—C81.7397 (19)C1—C21.386 (2)
S1—C41.7753 (15)C2—C31.375 (2)
S1—C51.8135 (19)C2—H20.9300
O1—C61.2207 (19)C5—C61.515 (2)
N1—C11.340 (2)C5—H5A0.9700
N1—H1A0.85 (2)C5—H5B0.9700
N1—H1B0.83 (2)C7—C121.382 (2)
N2—C31.346 (2)C7—C81.388 (2)
N2—H2A0.81 (3)C8—C91.383 (3)
N2—H2B0.85 (3)C9—C101.371 (3)
N3—C41.327 (2)C9—H90.9300
N3—C11.359 (2)C10—C111.382 (3)
N4—C41.318 (2)C10—H100.9300
N4—C31.360 (2)C11—C121.384 (3)
N5—C61.340 (2)C11—H110.9300
N5—C71.417 (2)C12—H120.9300
N5—H50.85 (2)
C4—S1—C5103.22 (8)S1—C5—H5A108.5
C1—N1—H1A118.4 (15)C6—C5—H5B108.5
C1—N1—H1B116.7 (16)S1—C5—H5B108.5
H1A—N1—H1B123 (2)H5A—C5—H5B107.5
C3—N2—H2A116.6 (17)O1—C6—N5124.20 (15)
C3—N2—H2B118.0 (17)O1—C6—C5121.24 (15)
H2A—N2—H2B120 (2)N5—C6—C5114.56 (14)
C4—N3—C1115.11 (13)C12—C7—C8118.68 (15)
C4—N4—C3114.72 (13)C12—C7—N5121.45 (15)
C6—N5—C7125.63 (14)C8—C7—N5119.87 (15)
C6—N5—H5116.8 (13)C9—C8—C7121.22 (18)
C7—N5—H5117.5 (13)C9—C8—Cl1118.54 (15)
N1—C1—N3117.08 (15)C7—C8—Cl1120.20 (13)
N1—C1—C2121.83 (15)C10—C9—C8119.36 (19)
N3—C1—C2121.08 (14)C10—C9—H9120.3
C3—C2—C1117.94 (14)C8—C9—H9120.3
C3—C2—H2121.0C9—C10—C11120.31 (17)
C1—C2—H2121.0C9—C10—H10119.8
N2—C3—N4115.59 (15)C11—C10—H10119.8
N2—C3—C2122.48 (15)C10—C11—C12120.09 (19)
N4—C3—C2121.90 (15)C10—C11—H11120.0
N4—C4—N3129.18 (14)C12—C11—H11120.0
N4—C4—S1118.71 (12)C7—C12—C11120.34 (18)
N3—C4—S1112.10 (11)C7—C12—H12119.8
C6—C5—S1115.29 (12)C11—C12—H12119.8
C6—C5—H5A108.5
C4—N3—C1—N1179.80 (16)C7—N5—C6—C5178.60 (16)
C4—N3—C1—C21.4 (2)S1—C5—C6—O1106.66 (16)
N1—C1—C2—C3178.13 (17)S1—C5—C6—N574.10 (18)
N3—C1—C2—C30.6 (3)C6—N5—C7—C1247.4 (2)
C4—N4—C3—N2179.24 (16)C6—N5—C7—C8133.27 (18)
C4—N4—C3—C22.5 (2)C12—C7—C8—C90.5 (2)
C1—C2—C3—N2179.19 (18)N5—C7—C8—C9179.80 (15)
C1—C2—C3—N42.7 (3)C12—C7—C8—Cl1178.14 (12)
C3—N4—C4—N30.3 (2)N5—C7—C8—Cl12.5 (2)
C3—N4—C4—S1178.72 (11)C7—C8—C9—C100.0 (3)
C1—N3—C4—N41.7 (2)Cl1—C8—C9—C10177.71 (14)
C1—N3—C4—S1176.86 (11)C8—C9—C10—C110.5 (3)
C5—S1—C4—N415.56 (15)C9—C10—C11—C120.5 (3)
C5—S1—C4—N3165.73 (12)C8—C7—C12—C110.5 (2)
C4—S1—C5—C689.86 (13)N5—C7—C12—C11179.79 (15)
C7—N5—C6—O10.6 (3)C10—C11—C12—C70.0 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N5—H5···N40.85 (2)2.12 (2)2.898 (2)152 (2)
N2—H2A···Cl10.81 (3)2.81 (2)3.493 (2)143 (2)
N1—H1A···N3i0.85 (2)2.21 (2)3.058 (2)174 (2)
N1—H1B···O1ii0.83 (2)2.21 (2)2.992 (2)157 (2)
N2—H2A···O1iii0.81 (3)2.56 (2)3.095 (2)124 (2)
C2—H2···O1ii0.932.643.353 (2)134
Symmetry codes: (i) x, y, z+1; (ii) x1, y1, z; (iii) x1, y, z.
 

Acknowledgements

The authors thank the TBI X-ray facility, CAS in Crystallography and Biophysics, University of Madras, India, for the data collection. SS and DV thank the UGC (SAP–CAS) for the departmental facilities. SS also thanks the UGC for the award of a meritorious fellowship.

References

First citationBlumenkopf, T. A., Mueller, E. E. & Roskamp, E. J. (2003). Patent US20030191307A1.  Google Scholar
First citationBruker (2008). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationGangjee, A., Yang, J., McGuire, J. J. & Kisliuk, R. L. (2006). Bioorg. Med. Chem. 14, 8590–8598.  CrossRef PubMed CAS Google Scholar
First citationGao, L.-X., Fang, G.-J., Feng, J.-G., Liang, D. & Wang, W. (2008). Acta Cryst. E64, o760.  Web of Science CSD CrossRef IUCr Journals Google Scholar
First citationGroom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179.  Web of Science CSD CrossRef IUCr Journals Google Scholar
First citationHocková, D., Holý, A. N., Masojídková, M., Andrei, G., Snoeck, R., De Clercq, E. & Balzarini, J. (2004). Bioorg. Med. Chem. 12, 3197–3202.  Web of Science PubMed Google Scholar
First citationLi, Q., Wang, W., Wang, H., Gao, Y. & Qiu, H. (2009). Acta Cryst. E65, o959.  Web of Science CSD CrossRef IUCr Journals Google Scholar
First citationMacrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466–470.  Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
First citationParsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationPerales, J. B., Freeman, J., Bacchi, C. J., Bowling, T., Don, R., Gaukel, E., Mercer, L., Moore, J. A. III, Nare, B., Nguyen, T. M., Noe, R. A., Randolph, R., Rewerts, C., Wring, S. A., Yarlett, N. & Jacobs, R. T. (2011). Bioorg. Med. Chem. Lett. 21, 2816–2819.  CrossRef CAS PubMed Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationSpek, A. L. (2009). Acta Cryst. D65, 148–155.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSubasri, S., Kumar, T. A., Sinha, B. N., Jayaprakash, V. & Velmurugan, D. (2014). Acta Cryst. E70, o850.  CSD CrossRef IUCr Journals Google Scholar
First citationTimiri, A. K., Sinha, B. N. & Jayaprakash, V. (2016). Eur. J. Med. Chem. 117, 125–143.  CrossRef CAS PubMed Google Scholar
First citationXu, L.-B., Sun, W., Liu, H.-Y., Wang, L.-L., Xiao, J.-H., Yang, X.-H. & Li, S. (2010). Chin. Chem. Lett. 21, 1318–1321.  CrossRef CAS Google Scholar

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