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Volume 69 
Part 12 
Pages o1743-o1744  
December 2013  

Received 24 October 2013
Accepted 30 October 2013
Online 6 November 2013

Open access

Raltegravir monohydrate

aDepartment of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, India, and bDepartment of Chemistry, Keene State College, 229 Main Street, Keene, NH 03435-2001, USA
Correspondence e-mail: jjasinski@keene.edu

The hydrated title compound [systematic name: N-(4-fluoro­benz­yl)-5-hy­droxy-1-methyl-2-{1-methyl-1-[(5-methyl-1,3,4-oxa­diazol-2-ylcarbon­yl)amino]­eth­yl}-6-oxo-1,6-di­hydro­pyrimidine-4-carb­oxamide monohydrate], C20H21FN6O5·H2O, is recognised as the first HIV integrase inhibitor. In the mol­ecule, the dihedral angles between the mean planes of the pyrimidine ring and the phenyl and oxa­diazole rings are 72.0 (1) and 61.8 (3)°, respectively. The mean plane of the oxa­diazole ring is twisted by 15.6 (3)° from that of the benzene ring, while the mean plane of amide group bound to the oxadiaole ring is twisted by 18.8 (3)° from its mean plane. Intra­molecular O-H...O and C-H...N hydrogen bonds are observed in the mol­ecule. The crystal packing features O-H...O hydrogen bonds, which include bifurcated O-H...(O,O) hydrogen bonds from one H atom of the water mol­ecule. In addition, N-H...O hydrogen bonds are observed involving the two amide groups. These inter­actions link the mol­ecules into chains along [010].

Related literature

For general background to and pharmacological properties of Raltegravir, see: Burger (2010[Burger, D. M. (2010). Exp. Opin. Drug Metab. Toxicol. 6, 1151-1160.]); Cocohoba & Dong (2008[Cocohoba, J. & Dong, B. J. (2008). Clin. Ther. 30, 1747-1765.]); Croxtall & Keam (2009[Croxtall, J. D. & Keam, S. J. (2009). Drugs, 69, 1059-1075.]); Evering & Markowitz (2008[Evering, T. H. & Markowitz, M. (2008). Exp. Opin. Invest. Drugs, 17, 413-422.]); Hicks & Gulick (2009[Hicks, C. & Gulick, R. M. (2009). Clin. Infect. Dis. 48, 931-939.]); Savarino (2006[Savarino, A. (2006). Exp. Opin. Invest. Drugs, 15, 1507-1522.]); Temesgen & Siraj (2008[Temesgen, Z. & Siraj, D. S. (2008). Ther. Clin. Risk Manage. 4, 493-500.]). For related structures, see: Fun et al. (2011[Fun, H.-K., Sumangala, V., Prasad, D. J., Poojary, B. & Chantrapromma, S. (2011). Acta Cryst. E67, o274.]); Shang et al. (2012[Shang, Z., Tao, X., Ha, J. & Yu, F. (2012). Acta Cryst. E68, o3175.]); Shang, Ha et al. (2011[Shang, Z., Ha, J., Yu, Y. & Zhao, X. (2011). Acta Cryst. E67, o1336.]); Shang, Qi et al. (2011[Shang, Z., Qi, S., Tao, X. & Zhang, G. (2011). Acta Cryst. E67, o1335.]); Thiruvalluvar et al. (2007[Thiruvalluvar, A., Subramanyam, M., Lingappa, B. & Kalluraya, B. (2007). Acta Cryst. E63, o3425.]). For standard bond lengths, see: Allen et al. (1987[Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1-19.]).

[Scheme 1]

Experimental

Crystal data
  • C20H21FN6O5·H2O

  • Mr = 462.44

  • Triclinic, [P \overline 1]

  • a = 8.3860 (6) Å

  • b = 11.8610 (9) Å

  • c = 12.1102 (9) Å

  • [alpha] = 110.481 (7)°

  • [beta] = 108.093 (7)°

  • [gamma] = 92.329 (6)°

  • V = 1057.44 (15) Å3

  • Z = 2

  • Mo K[alpha] radiation

  • [mu] = 0.12 mm-1

  • T = 173 K

  • 0.44 × 0.32 × 0.26 mm

Data collection
  • Agilent Xcalibur (Eos, Gemini) diffractometer

  • Absorption correction: multi-scan (CrysAlis PRO and CrysAlis RED; Agilent, 2012[Agilent (2012). CrysAlis PRO and CrysAlis RED. Agilent Technologies, Yarnton, England.]) Tmin = 0.890, Tmax = 1.000

  • 12734 measured reflections

  • 7007 independent reflections

  • 5042 reflections with I > 2[sigma](I)

  • Rint = 0.025

Refinement
  • R[F2 > 2[sigma](F2)] = 0.067

  • wR(F2) = 0.206

  • S = 1.03

  • 7007 reflections

  • 306 parameters

  • H-atom parameters constrained

  • [Delta][rho]max = 0.78 e Å-3

  • [Delta][rho]min = -0.39 e Å-3

Table 1
Hydrogen-bond geometry (Å, °)

D-H...A D-H H...A D...A D-H...A
O4-H4...O5 0.84 1.88 2.593 (2) 143
C20-H20C...N1 0.98 2.25 2.982 (3) 130
N1-H1...O5i 0.88 2.23 2.970 (2) 142
N4-H4A...O1Wii 0.88 2.48 3.074 (3) 126
C7-H7A...O1Wii 0.99 2.58 3.240 (3) 124
C10-H10...O5iii 0.95 2.50 3.393 (3) 158
C20-H20A...O4iv 0.98 2.46 3.394 (2) 160
C20-H20B...N6v 0.98 2.50 3.422 (3) 158
O1W-H1WA...O4vi 0.85 2.51 3.249 (3) 146
O1W-H1WA...O3vi 0.85 2.33 3.013 (3) 138
O1W-H1WB...O2 0.85 2.04 2.869 (2) 164
Symmetry codes: (i) -x+2, -y, -z+1; (ii) -x+2, -y+1, -z+1; (iii) -x+2, -y, -z+2; (iv) -x+1, -y, -z+1; (v) -x+1, -y, -z; (vi) x, y+1, z.

Data collection: CrysAlis PRO (Agilent, 2012[Agilent (2012). CrysAlis PRO and CrysAlis RED. Agilent Technologies, Yarnton, England.]); cell refinement: CrysAlis PRO; data reduction: CrysAlis RED (Agilent, 2012[Agilent (2012). CrysAlis PRO and CrysAlis RED. Agilent Technologies, Yarnton, England.]); program(s) used to solve structure: SUPERFLIP (Palatinus & Chapuis, 2007[Palatinus, L. & Chapuis, G. (2007). J. Appl. Cryst. 40, 786-790.]); program(s) used to refine structure: SHELXL2012 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]); software used to prepare material for publication: OLEX2.


Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: SJ5363 ).


Acknowledgements

TSY thanks the UOM for research facilities. HSY thanks Dr M. T. Swamy, Department of Chemistry, Sambhram Institute of Technology, Bengaluru, India, for a sample of the title compound. JPJ acknowledges the NSF-MRI program (grant No. CHE-1039027) for funds to purchase the X-ray diffractometer.

References

Agilent (2012). CrysAlis PRO and CrysAlis RED. Agilent Technologies, Yarnton, England.
Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1-19.
Burger, D. M. (2010). Exp. Opin. Drug Metab. Toxicol. 6, 1151-1160.  [CrossRef] [ChemPort]
Cocohoba, J. & Dong, B. J. (2008). Clin. Ther. 30, 1747-1765.  [Web of Science] [CrossRef] [PubMed] [ChemPort]
Croxtall, J. D. & Keam, S. J. (2009). Drugs, 69, 1059-1075.  [CrossRef] [PubMed] [ChemPort]
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.  [Web of Science] [CrossRef] [ChemPort] [IUCr Journals]
Evering, T. H. & Markowitz, M. (2008). Exp. Opin. Invest. Drugs, 17, 413-422.  [CrossRef] [ChemPort]
Fun, H.-K., Sumangala, V., Prasad, D. J., Poojary, B. & Chantrapromma, S. (2011). Acta Cryst. E67, o274.  [CSD] [CrossRef] [IUCr Journals]
Hicks, C. & Gulick, R. M. (2009). Clin. Infect. Dis. 48, 931-939.  [Web of Science] [CrossRef] [PubMed] [ChemPort]
Palatinus, L. & Chapuis, G. (2007). J. Appl. Cryst. 40, 786-790.  [Web of Science] [CrossRef] [ChemPort] [IUCr Journals]
Savarino, A. (2006). Exp. Opin. Invest. Drugs, 15, 1507-1522.  [CrossRef] [ChemPort]
Shang, Z., Ha, J., Yu, Y. & Zhao, X. (2011). Acta Cryst. E67, o1336.  [CSD] [CrossRef] [IUCr Journals]
Shang, Z., Qi, S., Tao, X. & Zhang, G. (2011). Acta Cryst. E67, o1335.  [CSD] [CrossRef] [IUCr Journals]
Shang, Z., Tao, X., Ha, J. & Yu, F. (2012). Acta Cryst. E68, o3175.  [CSD] [CrossRef] [IUCr Journals]
Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.  [CrossRef] [ChemPort] [IUCr Journals]
Temesgen, Z. & Siraj, D. S. (2008). Ther. Clin. Risk Manage. 4, 493-500.  [ChemPort]
Thiruvalluvar, A., Subramanyam, M., Lingappa, B. & Kalluraya, B. (2007). Acta Cryst. E63, o3425.  [CSD] [CrossRef] [IUCr Journals]


Acta Cryst (2013). E69, o1743-o1744   [ doi:10.1107/S1600536813029747 ]

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