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Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890

3-(2-Fluoro­phen­yl)-6-(phen­oxy­meth­yl)-1,2,4-triazolo[3,4-b][1,3,4]thia­diazole

aInstitute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry, Eberhard-Karls-University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany, and bDepartment of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, D-55099 Mainz, Germany
*Correspondence e-mail: stefan.laufer@uni-tuebingen.de

(Received 5 February 2008; accepted 6 February 2008; online 12 March 2008)

The crystal structure of the title compound, C16H11FN4OS, was synthesized in the course of our studies on 1,2,4-triazolo[3,4-b][1,3,4]thia­diazo­les as inhibitors of p38 mitogen-activated protein kinase (MAPK). The three-dimensional data obtained were used to generate a three-dimensional pharmacophore model for in silico database screening. The dihedral angles between the central heterocylic system and the fluoro­phenyl and phenyl rings are 20.21 (3) and 5.43 (1)°, respectively; the dihedral angle between the two benzene rings is 15.80 (4)°.

Related literature

Protein kinases (PK) are favoured targets for the development of new drugs (Hopkins & Groon, 2002[Hopkins, A. L. & Groon, C. R. (2002). Nat. Rev. Drug Discov. 1, 727-730.]) because the reversible protein-phospho­rylation by PK is an important control mechanism in the signal pathways of a cell (Laufer et al., 2005[Laufer, S. A., Domeyer, D. M., Scior, T. R. F., Albrecht, W. & Hauser, D. R. J. (2005). J. Med. Chem. 48, 710-722.]). The [1,2,4]triazolo[3,4-b][1,3,4]thia­diazole nucleus is associated with diverse biological activities (Malhotra et al., 2003[Malhotra, S., Manher, V. & Chadha, V. K. (2003). Indian J. Heterocycl. Chem. 12, 257-262.]). For the preparation of the title compound, see: Invidiata et al. (1997[Invidiata, F. P., Furno, G., Lampronti, I. & Simoni, D. (1997). J. Heterocycl. Chem. 34, 1255-1258.]); Malhotra et al. (2003[Malhotra, S., Manher, V. & Chadha, V. K. (2003). Indian J. Heterocycl. Chem. 12, 257-262.]).

[Scheme 1]

Experimental

Crystal data
  • C16H11FN4OS

  • Mr = 326.35

  • Monoclinic, P 21 /n

  • a = 10.8551 (6) Å

  • b = 12.1899 (3) Å

  • c = 11.6667 (6) Å

  • β = 110.857 (5)°

  • V = 1442.61 (11) Å3

  • Z = 4

  • Cu Kα radiation

  • μ = 2.19 mm−1

  • T = 193 (2) K

  • 0.58 × 0.51 × 0.26 mm

Data collection
  • Enraf–Nonius CAD-4 diffractometer

  • Absorption correction: ψ scan (CORINC; Dräger & Gattow, 1971[Dräger, M. & Gattow, G. (1971). Acta Chem. Scand. 25, 761-762.]) Tmin = 0.61, Tmax = 0.99 (expected range = 0.348–0.565)

  • 2883 measured reflections

  • 2736 independent reflections

  • 2583 reflections with I > 2σ(I)

  • Rint = 0.037

  • 3 standard reflections frequency: 60 min intensity decay: 4%

Refinement
  • R[F2 > 2σ(F2)] = 0.048

  • wR(F2) = 0.135

  • S = 1.06

  • 2736 reflections

  • 209 parameters

  • H-atom parameters constrained

  • Δρmax = 0.43 e Å−3

  • Δρmin = −0.43 e Å−3

Data collection: CAD-4 Software (Enraf–Nonius, 1989[Enraf-Nonius (1989). CAD-4 Software. Enraf-Nonius, Delft, The Netherlands.]); cell refinement: CAD-4 Software; data reduction: CORINC (Dräger & Gattow, 1971[Dräger, M. & Gattow, G. (1971). Acta Chem. Scand. 25, 761-762.]); program(s) used to solve structure: SIR92 (Altomare et al., 1994[Altomare, A., Cascarano, G., Giacovazzo, C., Guagliardi, A., Burla, M. C., Polidori, G. & Camalli, M. (1994). J. Appl. Cryst. 27, 435-436.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: PLATON (Spek, 2003[Spek, A. L. (2003). J. Appl. Cryst. 36, 7-13.]); software used to prepare material for publication: SHELXL97.

Supporting information


Comment top

Continued interest in development of small molecule inhibitors of p38 mitogen-activated protein (MAP) kinase is based on the central role of this enzyme in inflammatory cell signalling. Activation of p38 leads to an increase production of pro-inflammatory cytokines such as TNF-alpha and IL-1beta. Many different diseases have their seeds in an overactive immune response. Prominent examples like psoriasis, rheumatoid arthritis and inflammatory bowel disease turn it into a still prominent target for antiinflammatory drug discovery. 3-(2-chlorophenyl)-6-((4-methoxyphenoxy)methyl)-[1,2,4]triazolo[3,4-b] [1,3,4]thiadiazole was identified as potential hit in a virtual screening and the [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole core therefore chosen as starting point for a medicinal chemistry program. To gain more information about structure-activity relationship, a series of compounds were synthesized and tested.

The synthesis of 1 (Figure 1) was started from the substituted hydrazide, which was treated with carbon disulfide. Cyclization followed by reaction with hydrazine. The final product 2 was synthesized by reaction of 1 with 2-phenoxyacetic acid in presence of phosphorus oxychloride.

Of special interest was the proposed binding mode of disubstituted compound and a crystal structure of compound 2 was prepared (Figure 2).

Related literature top

Protein kinases (PK) are favoured targets for the development of new drugs (Hopkins & Groon, 2002) because the reversible protein-phosphorylation by PK is an important control mechanism in signal pathways of a cell (Laufer et al., 2005). The [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole nucleus is associated with diverse biological activities (Malhotra et al., 2003). For the preparation of the title compound, see: Invidiata et al. (1997); Malhotra et al. (2003).

Experimental top

The synthesis of 3-(2-fluorophenyl)-6-(phenoxymethyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole was started from 2-fluorobenzohydrazide. Carbon disulfide (55.0 mmol) was added slowly to a solution of the hydrazide (36.0 mmol) in absolute ethanol (70 ml) containing potassium hydroxid (55.0 mmol). The resulting mixture was stirred over night at room temperature, then cooled and diluted with ether (100 ml). Potassium 2-(2-fluorobenzoyl)hydrazinecarbodithioate precipitated and was collected by filtration, washed with diethyl ether and dried.

A mixture containing potassium dithiocarbazinate (16.0 mmol) suspended in water (2 ml) and hydrazine hydrate (99%, 32.0 mmol) was heated under gentle reflux for 2 h. It was cooled to room temperature and diluted with water (80 ml) and acidified with concentrated hydrochloric acid. Thick white solid mass separated out. It was collected by filtration, washed with water and recrystallized from ethanol to get 4-amino-5-(2-fluorophenyl)-4H-1,2,4-triazole-3-thiol 1. (Invidiata et al., 1997)

For the preparation of the title compound, a mixture of 1 (5.0 mmol), 2-phenoxyacetic acid (1.0 mmol) and phosphorus oxychloride (10 ml) was refluxed for 6 h, cooled to room temperature and poured onto crushed ice. The solid product separated out and was collected by filtration, washed with aqueous NaOH solution (20 ml, 2 M) and then with water, dried and recrystallized from ethanol 2. (Malhotra et al., 2003)

Crystals of 2 for X-ray analysis precipitated slowly as brown platelets from ethanol at room temperature.

Refinement top

Hydrogen atoms were placed at calculated positions with C—H=0.95A% (aromatic) or 0.99 Å (sp3 C-atom). All H atoms were refined with isotropic displacement parameters set at 1.2 times of the Ueq of the parent atom.

Computing details top

Data collection: CAD-4 Software (Enraf–Nonius, 1989); cell refinement: CAD-4 Software (Enraf–Nonius, 1989); data reduction: CORINC (Dräger & Gattow, 1971); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. Synthesis of compounds 1 and 2.
[Figure 2] Fig. 2. Perspective view of 2. Displacement ellipsoids are drawn at the 50% probability level. H atoms are depicted as circles of arbitrary size.
3-(2-Fluorophenyl)-6-(phenoxymethyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole top
Crystal data top
C16H11FN4OSF(000) = 672
Mr = 326.35Dx = 1.503 Mg m3
Monoclinic, P21/nCu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ynCell parameters from 25 reflections
a = 10.8551 (6) Åθ = 65–70°
b = 12.1899 (3) ŵ = 2.19 mm1
c = 11.6667 (6) ÅT = 193 K
β = 110.857 (5)°Plate, light brown
V = 1442.61 (11) Å30.58 × 0.51 × 0.26 mm
Z = 4
Data collection top
Enraf–Nonius CAD-4
diffractometer
2583 reflections with I > 2s(I)
Radiation source: rotating anodeRint = 0.037
Graphite monochromatorθmax = 69.9°, θmin = 4.8°
ω/2θ scansh = 013
Absorption correction: ψ scan
(CORINC; Dräger & Gattow, 1971)
k = 014
Tmin = 0.61, Tmax = 0.99l = 1413
2883 measured reflections3 standard reflections every 60 min
2736 independent reflections intensity decay: 4%
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.048H-atom parameters constrained
wR(F2) = 0.135 w = 1/[σ2(Fo2) + (0.0847P)2 + 0.6884P]
where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max < 0.001
2736 reflectionsΔρmax = 0.43 e Å3
209 parametersΔρmin = 0.43 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0071 (8)
Crystal data top
C16H11FN4OSV = 1442.61 (11) Å3
Mr = 326.35Z = 4
Monoclinic, P21/nCu Kα radiation
a = 10.8551 (6) ŵ = 2.19 mm1
b = 12.1899 (3) ÅT = 193 K
c = 11.6667 (6) Å0.58 × 0.51 × 0.26 mm
β = 110.857 (5)°
Data collection top
Enraf–Nonius CAD-4
diffractometer
2583 reflections with I > 2s(I)
Absorption correction: ψ scan
(CORINC; Dräger & Gattow, 1971)
Rint = 0.037
Tmin = 0.61, Tmax = 0.993 standard reflections every 60 min
2883 measured reflections intensity decay: 4%
2736 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0480 restraints
wR(F2) = 0.135H-atom parameters constrained
S = 1.06Δρmax = 0.43 e Å3
2736 reflectionsΔρmin = 0.43 e Å3
209 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
xyzUiso*/Ueq
N10.65749 (15)0.29912 (12)0.27951 (14)0.0311 (4)
C20.62295 (17)0.25592 (16)0.17147 (17)0.0324 (4)
S30.63057 (5)0.11269 (4)0.16086 (4)0.0375 (2)
C40.68622 (19)0.11015 (15)0.31907 (19)0.0358 (4)
N50.72177 (18)0.03789 (14)0.40767 (17)0.0445 (4)
N60.75709 (18)0.09854 (14)0.51539 (17)0.0426 (4)
C70.74119 (17)0.20439 (15)0.48900 (18)0.0331 (4)
N80.69477 (14)0.21442 (12)0.36353 (14)0.0306 (4)
C90.58296 (19)0.32345 (16)0.05735 (17)0.0358 (4)
H9A0.51900.38060.05930.043*
H9B0.66070.35960.04840.043*
O100.52441 (15)0.24906 (12)0.04087 (12)0.0433 (4)
C110.50482 (17)0.28429 (16)0.15846 (17)0.0326 (4)
C120.45545 (19)0.20490 (17)0.24815 (18)0.0376 (4)
H120.43660.13330.22660.045*
C130.4337 (2)0.23046 (19)0.36915 (19)0.0436 (5)
H130.40120.17590.43080.052*
C140.4591 (2)0.3350 (2)0.40103 (19)0.0451 (5)
H140.44420.35240.48430.054*
C150.5060 (2)0.41365 (19)0.3114 (2)0.0439 (5)
H150.52200.48580.33360.053*
C160.5303 (2)0.38932 (16)0.1887 (2)0.0378 (5)
H160.56370.44370.12710.045*
C170.77445 (17)0.29576 (16)0.57653 (17)0.0323 (4)
C180.76314 (19)0.40498 (16)0.53692 (18)0.0345 (4)
H180.73120.42040.45150.041*
C190.79764 (19)0.49076 (17)0.61989 (18)0.0390 (4)
H190.78950.56420.59090.047*
C200.8439 (2)0.47064 (19)0.74481 (19)0.0426 (5)
H200.86640.52970.80160.051*
C210.8569 (2)0.3633 (2)0.78588 (19)0.0451 (5)
H210.88950.34800.87130.054*
C220.8224 (2)0.27895 (18)0.70268 (19)0.0399 (5)
F230.83678 (15)0.17577 (12)0.74746 (12)0.0608 (4)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0311 (7)0.0273 (8)0.0325 (8)0.0000 (6)0.0082 (6)0.0011 (6)
C20.0281 (8)0.0299 (9)0.0381 (10)0.0027 (7)0.0105 (7)0.0040 (7)
S30.0402 (3)0.0294 (3)0.0430 (3)0.00168 (17)0.0147 (2)0.00653 (18)
C40.0330 (10)0.0276 (10)0.0457 (11)0.0003 (7)0.0126 (8)0.0033 (8)
N50.0482 (10)0.0293 (9)0.0522 (10)0.0041 (7)0.0134 (8)0.0039 (7)
N60.0453 (10)0.0317 (9)0.0464 (10)0.0027 (7)0.0111 (8)0.0066 (7)
C70.0283 (8)0.0320 (10)0.0375 (10)0.0007 (7)0.0099 (7)0.0059 (7)
N80.0279 (7)0.0244 (7)0.0375 (8)0.0009 (6)0.0092 (6)0.0011 (6)
C90.0390 (10)0.0318 (10)0.0325 (10)0.0051 (7)0.0075 (8)0.0044 (7)
O100.0606 (9)0.0355 (8)0.0316 (7)0.0147 (6)0.0137 (6)0.0050 (6)
C110.0304 (9)0.0348 (10)0.0322 (9)0.0007 (7)0.0107 (7)0.0011 (7)
C120.0398 (10)0.0348 (10)0.0375 (10)0.0024 (8)0.0129 (8)0.0026 (8)
C130.0416 (10)0.0532 (13)0.0341 (10)0.0000 (9)0.0112 (8)0.0062 (9)
C140.0370 (10)0.0612 (14)0.0369 (11)0.0034 (10)0.0129 (8)0.0081 (10)
C150.0377 (10)0.0433 (11)0.0495 (12)0.0011 (9)0.0141 (9)0.0132 (9)
C160.0358 (10)0.0340 (11)0.0425 (11)0.0018 (7)0.0125 (8)0.0018 (8)
C170.0262 (8)0.0365 (10)0.0334 (9)0.0009 (7)0.0097 (7)0.0038 (7)
C180.0345 (9)0.0356 (10)0.0314 (9)0.0036 (8)0.0094 (7)0.0030 (7)
C190.0412 (10)0.0364 (10)0.0378 (10)0.0054 (8)0.0119 (8)0.0006 (8)
C200.0404 (10)0.0500 (13)0.0377 (10)0.0005 (9)0.0144 (8)0.0083 (9)
C210.0468 (11)0.0600 (14)0.0293 (10)0.0021 (10)0.0144 (8)0.0045 (9)
C220.0384 (10)0.0428 (11)0.0384 (10)0.0014 (8)0.0136 (8)0.0110 (9)
F230.0822 (10)0.0482 (8)0.0443 (7)0.0076 (7)0.0128 (7)0.0186 (6)
Geometric parameters (Å, º) top
N1—C21.292 (2)C13—C141.382 (3)
N1—N81.381 (2)C13—H130.9500
C2—C91.492 (3)C14—C151.376 (3)
C2—S31.7544 (19)C14—H140.9500
S3—C41.726 (2)C15—C161.392 (3)
C4—N51.307 (3)C15—H150.9500
C4—N81.363 (2)C16—H160.9500
N5—N61.389 (3)C17—C221.391 (3)
N6—C71.324 (2)C17—C181.400 (3)
C7—N81.373 (2)C18—C191.383 (3)
C7—C171.467 (3)C18—H180.9500
C9—O101.422 (2)C19—C201.384 (3)
C9—H9A0.9900C19—H190.9500
C9—H9B0.9900C20—C211.384 (3)
O10—C111.380 (2)C20—H200.9500
C11—C161.382 (3)C21—C221.371 (3)
C11—C121.385 (3)C21—H210.9500
C12—C131.381 (3)C22—F231.349 (2)
C12—H120.9500
C2—N1—N8107.31 (15)C12—C13—H13119.8
N1—C2—C9122.45 (17)C14—C13—H13119.8
N1—C2—S3118.02 (15)C15—C14—C13119.5 (2)
C9—C2—S3119.48 (13)C15—C14—H14120.2
C4—S3—C287.12 (9)C13—C14—H14120.2
N5—C4—N8111.49 (18)C14—C15—C16121.1 (2)
N5—C4—S3138.59 (15)C14—C15—H15119.4
N8—C4—S3109.92 (14)C16—C15—H15119.4
C4—N5—N6105.39 (16)C11—C16—C15118.55 (19)
C7—N6—N5109.71 (16)C11—C16—H16120.7
N6—C7—N8107.62 (17)C15—C16—H16120.7
N6—C7—C17126.80 (18)C22—C17—C18116.43 (19)
N8—C7—C17125.48 (17)C22—C17—C7122.11 (18)
C4—N8—C7105.78 (16)C18—C17—C7121.42 (17)
C4—N8—N1117.63 (15)C19—C18—C17121.19 (18)
C7—N8—N1136.59 (15)C19—C18—H18119.4
O10—C9—C2105.77 (15)C17—C18—H18119.4
O10—C9—H9A110.6C18—C19—C20120.62 (19)
C2—C9—H9A110.6C18—C19—H19119.7
O10—C9—H9B110.6C20—C19—H19119.7
C2—C9—H9B110.6C21—C20—C19119.1 (2)
H9A—C9—H9B108.7C21—C20—H20120.4
C11—O10—C9117.99 (15)C19—C20—H20120.4
O10—C11—C16124.62 (17)C22—C21—C20119.70 (19)
O10—C11—C12114.51 (17)C22—C21—H21120.2
C16—C11—C12120.87 (18)C20—C21—H21120.2
C13—C12—C11119.58 (19)F23—C22—C21117.38 (19)
C13—C12—H12120.2F23—C22—C17119.7 (2)
C11—C12—H12120.2C21—C22—C17122.9 (2)
C12—C13—C14120.3 (2)
N8—N1—C2—C9176.82 (15)C9—O10—C11—C12175.96 (17)
N8—N1—C2—S30.50 (19)O10—C11—C12—C13179.06 (17)
N1—C2—S3—C40.04 (15)C16—C11—C12—C131.2 (3)
C9—C2—S3—C4177.45 (15)C11—C12—C13—C141.0 (3)
C2—S3—C4—N5179.1 (2)C12—C13—C14—C150.1 (3)
C2—S3—C4—N80.59 (14)C13—C14—C15—C161.0 (3)
N8—C4—N5—N60.9 (2)O10—C11—C16—C15179.97 (18)
S3—C4—N5—N6179.41 (19)C12—C11—C16—C150.4 (3)
C4—N5—N6—C70.4 (2)C14—C15—C16—C110.8 (3)
N5—N6—C7—N80.2 (2)N6—C7—C17—C223.4 (3)
N5—N6—C7—C17176.25 (17)N8—C7—C17—C22179.30 (17)
N5—C4—N8—C71.0 (2)N6—C7—C17—C18174.60 (19)
S3—C4—N8—C7179.19 (12)N8—C7—C17—C181.2 (3)
N5—C4—N8—N1178.73 (15)C22—C17—C18—C190.3 (3)
S3—C4—N8—N11.1 (2)C7—C17—C18—C19178.43 (17)
N6—C7—N8—C40.7 (2)C17—C18—C19—C200.3 (3)
C17—C7—N8—C4175.79 (17)C18—C19—C20—C210.9 (3)
N6—C7—N8—N1178.96 (18)C19—C20—C21—C220.8 (3)
C17—C7—N8—N14.5 (3)C20—C21—C22—F23179.92 (18)
C2—N1—N8—C41.0 (2)C20—C21—C22—C170.2 (3)
C2—N1—N8—C7179.34 (19)C18—C17—C22—F23179.53 (17)
N1—C2—C9—O10167.07 (16)C7—C17—C22—F231.4 (3)
S3—C2—C9—O1015.6 (2)C18—C17—C22—C210.3 (3)
C2—C9—O10—C11165.85 (15)C7—C17—C22—C21178.45 (19)
C9—O10—C11—C164.3 (3)

Experimental details

Crystal data
Chemical formulaC16H11FN4OS
Mr326.35
Crystal system, space groupMonoclinic, P21/n
Temperature (K)193
a, b, c (Å)10.8551 (6), 12.1899 (3), 11.6667 (6)
β (°) 110.857 (5)
V3)1442.61 (11)
Z4
Radiation typeCu Kα
µ (mm1)2.19
Crystal size (mm)0.58 × 0.51 × 0.26
Data collection
DiffractometerEnraf–Nonius CAD-4
diffractometer
Absorption correctionψ scan
(CORINC; Dräger & Gattow, 1971)
Tmin, Tmax0.61, 0.99
No. of measured, independent and
observed [I > 2s(I)] reflections
2883, 2736, 2583
Rint0.037
(sin θ/λ)max1)0.609
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.048, 0.135, 1.06
No. of reflections2736
No. of parameters209
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.43, 0.43

Computer programs: CAD-4 Software (Enraf–Nonius, 1989), CORINC (Dräger & Gattow, 1971), SIR92 (Altomare et al., 1994), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2003).

 

Acknowledgements

We are grateful to BERGHOF Products & Instruments GmbH, Eningen, Germany for the BR-25 high pressure reactor and for technical support.

References

First citationAltomare, A., Cascarano, G., Giacovazzo, C., Guagliardi, A., Burla, M. C., Polidori, G. & Camalli, M. (1994). J. Appl. Cryst. 27, 435–436.  CrossRef Web of Science IUCr Journals Google Scholar
First citationDräger, M. & Gattow, G. (1971). Acta Chem. Scand. 25, 761–762.  Google Scholar
First citationEnraf–Nonius (1989). CAD-4 Software. Enraf–Nonius, Delft, The Netherlands.  Google Scholar
First citationHopkins, A. L. & Groon, C. R. (2002). Nat. Rev. Drug Discov. 1, 727–730.  Web of Science CrossRef PubMed CAS Google Scholar
First citationInvidiata, F. P., Furno, G., Lampronti, I. & Simoni, D. (1997). J. Heterocycl. Chem. 34, 1255–1258.  CrossRef CAS Google Scholar
First citationLaufer, S. A., Domeyer, D. M., Scior, T. R. F., Albrecht, W. & Hauser, D. R. J. (2005). J. Med. Chem. 48, 710–722.  Web of Science CrossRef PubMed CAS Google Scholar
First citationMalhotra, S., Manher, V. & Chadha, V. K. (2003). Indian J. Heterocycl. Chem. 12, 257–262.  Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSpek, A. L. (2003). J. Appl. Cryst. 36, 7–13.  Web of Science CrossRef CAS IUCr Journals Google Scholar

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