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

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1,4-Di­methyl-2-phenyl-6,7-di­hydro-1H-pyrazolo­[4,3-b]pyridine-3,5(2H,4H)-dione

aEberhard-Karls-University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany, and bUniversity Mainz, Institut of Organic Chemistry, Duesbergweg 10-14, 55099 Mainz, Germany
*Correspondence e-mail: stefan.laufer@uni-tuebingen.de

(Received 5 September 2011; accepted 5 September 2011; online 14 September 2011)

The mean plane of the pyrazolone ring [maximum deviation = 0.054 (1) Å] of the title compound, C14H15N3O2, is oriented at a dihedral angle of 36.05 (7)° with respect to the phenyl ring. The methyl group is slightly disposed [distance = 0.864 (2) Å] out of the mean plane of the pyrazolone ring to which it is attached.

Related literature

For the biological activity of pyrazolone derivates (e.g. dipyrone), see: Pierre et al. (2007[Pierre, S. C., Schmidt, R., Brenneis, C., Michaelis, M., Geisslinger, G. & Scholich, K. (2007). Br. J. Pharmacol. 151, 494-503.]). For general methods of clevage of N-Cbz protected amines see: Greene & Wuts (1999[Greene, T. W. & Wuts, P. G. M. (1999). Protective Groups in Organic Synthesis, Vol. 3. New York: John Wiley & Sons, Inc.]). For conversion of N-Cbz-protected amines into N-t-Boc-protected amines, see: Sakaitani et al. (1988[Sakaitani, M., Hori, K. & Ohfune, Y. (1988). Tetrahedron Lett. 29, 2983-2984.]).

[Scheme 1]

Experimental

Crystal data
  • C14H15N3O2

  • Mr = 257.29

  • Monoclinic, C c

  • a = 8.9721 (7) Å

  • b = 21.7653 (19) Å

  • c = 7.3725 (5) Å

  • β = 120.214 (5)°

  • V = 1244.12 (17) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.10 mm−1

  • T = 193 K

  • 0.45 × 0.17 × 0.16 mm

Data collection
  • Stoe IPDS 2T diffractometer

  • 4103 measured reflections

  • 1623 independent reflections

  • 1541 reflections with I > 2σ(I)

  • Rint = 0.036

Refinement
  • R[F2 > 2σ(F2)] = 0.027

  • wR(F2) = 0.071

  • S = 1.04

  • 1623 reflections

  • 174 parameters

  • 2 restraints

  • H-atom parameters constrained

  • Δρmax = 0.18 e Å−3

  • Δρmin = −0.14 e Å−3

Data collection: X-AREA (Stoe, 2010[Stoe (2010). X-AREA and X-RED. Stoe & Cie GmbH, Darmstadt, Germany.]); cell refinement: X-AREA; data reduction: X-RED (Stoe, 2010[Stoe (2010). X-AREA and X-RED. Stoe & Cie GmbH, Darmstadt, Germany.]); program(s) used to solve structure: SIR97 (Altomare et al., 1999[Altomare, A., Burla, M. C., Camalli, M., Cascarano, G. L., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G., Polidori, G. & Spagna, R. (1999). J. Appl. Cryst. 32, 115-119.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]); software used to prepare material for publication: PLATON.

Supporting information


Comment top

Pyrazolone derivates are widely known as potent analgesic drugs (Pierre et al., 2007). By transforming the protection group from a N-Cbz group into a N-t-Boc group in an one pot synthesis (Sakaitani et al., 1988) with the structure 3-(4-((benzyloxycarbonyl)(methyl)amino)-2-methyl-5-oxo-1-phenyl-2,5-dihydro-1H-pyrazol-3-yl)propanoic acid, a ringclosure to sixmembered ring was formed. For further investigation, we omitted the step of conversion and performed a direct clevage reaction (Greene & Wuts, 1999) leading to the title compound.

The pyrazolone ring of the anellated ringsystem is oriented at a dihedral angle of 36.05 (7)° with respect to the phenyl ring. The methyl group (C17) shows a distance of 0.864 (2) Å to the least square plane of the pyrazolone ring system.

Related literature top

For the biological activity of pyrazolone derivates (e.g. dipyrone), see: Pierre et al. (2007). For general methods of clevage of N-Cbz protected amines see: Greene & Wuts (1999). For conversion of N-Cbz-protected amines into N-t-Boc-protected amines, see: Sakaitani et al. (1988).

Experimental top

The compound was prepared by palladium catalzyed cleaverage of a N-Cbz protected amine (Greene & Wuts, 1999). 3-(4-((Benzyloxycarbonyl)(methyl)amino)-2-methyl-5-oxo-1-phenyl-2,5-dihydro-1H-pyrazol-3-yl)propanoic acid (0.74 g, 1.81 mmol) and palladium on activated carbon (10%, 0.19 g, 0.18 mmol) were dissolved in 40 ml ethyl acetate under a hydrogen atmosphere (1 atm). The mixture was stirred for 12 h with regular TLC monitoring, then filtered and concentrated. The resulting residue was purified by flash chromatography (SiO2, ethyl acetate/isopropyl alcohol 1:1). Crystals of the title compound were obtained by slow evaporation of ethanol at room temperature.

Refinement top

In the absence of anomalous scatterers, Friedel pairs were merged. Hydrogen atoms were placed at calculated positions with C—H = 0.95 Å (aromatic) or 0.98–0.99 Å (sp3 C-atom). All H atoms were refined in the riding-model approximation with isotropic displacement parameters set at 1.2–1.5 times of the Ueq of the parent atom.

Structure description top

Pyrazolone derivates are widely known as potent analgesic drugs (Pierre et al., 2007). By transforming the protection group from a N-Cbz group into a N-t-Boc group in an one pot synthesis (Sakaitani et al., 1988) with the structure 3-(4-((benzyloxycarbonyl)(methyl)amino)-2-methyl-5-oxo-1-phenyl-2,5-dihydro-1H-pyrazol-3-yl)propanoic acid, a ringclosure to sixmembered ring was formed. For further investigation, we omitted the step of conversion and performed a direct clevage reaction (Greene & Wuts, 1999) leading to the title compound.

The pyrazolone ring of the anellated ringsystem is oriented at a dihedral angle of 36.05 (7)° with respect to the phenyl ring. The methyl group (C17) shows a distance of 0.864 (2) Å to the least square plane of the pyrazolone ring system.

For the biological activity of pyrazolone derivates (e.g. dipyrone), see: Pierre et al. (2007). For general methods of clevage of N-Cbz protected amines see: Greene & Wuts (1999). For conversion of N-Cbz-protected amines into N-t-Boc-protected amines, see: Sakaitani et al. (1988).

Computing details top

Data collection: X-AREA (Stoe, 2010); cell refinement: X-AREA (Stoe, 2010); data reduction: X-RED (Stoe, 2010); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. View of compound I. Displacement ellipsoids are drawn at the 50% probability level.
1,4-Dimethyl-2-phenyl-6,7-dihydro-1H-pyrazolo[4,3-b]pyridine- 3,5(2H,4H)-dione top
Crystal data top
C14H15N3O2F(000) = 544
Mr = 257.29Dx = 1.374 Mg m3
Monoclinic, CcMo Kα radiation, λ = 0.71073 Å
Hall symbol: C -2ycCell parameters from 6605 reflections
a = 8.9721 (7) Åθ = 2.8–29.3°
b = 21.7653 (19) ŵ = 0.10 mm1
c = 7.3725 (5) ÅT = 193 K
β = 120.214 (5)°Plate, colourless
V = 1244.12 (17) Å30.45 × 0.17 × 0.16 mm
Z = 4
Data collection top
Stoe IPDS 2T
diffractometer
1541 reflections with I > 2σ(I)
Radiation source: sealed TubeRint = 0.036
Graphite monochromatorθmax = 28.9°, θmin = 2.8°
Detector resolution: 6.67 pixels mm-1h = 1212
rotation method scansk = 2925
4103 measured reflectionsl = 910
1623 independent reflections
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)] = 0.027Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.071H-atom parameters constrained
S = 1.04 w = 1/[σ2(Fo2) + (0.0454P)2 + 0.1582P]
where P = (Fo2 + 2Fc2)/3
1623 reflections(Δ/σ)max < 0.001
174 parametersΔρmax = 0.18 e Å3
2 restraintsΔρmin = 0.14 e Å3
Crystal data top
C14H15N3O2V = 1244.12 (17) Å3
Mr = 257.29Z = 4
Monoclinic, CcMo Kα radiation
a = 8.9721 (7) ŵ = 0.10 mm1
b = 21.7653 (19) ÅT = 193 K
c = 7.3725 (5) Å0.45 × 0.17 × 0.16 mm
β = 120.214 (5)°
Data collection top
Stoe IPDS 2T
diffractometer
1541 reflections with I > 2σ(I)
4103 measured reflectionsRint = 0.036
1623 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0272 restraints
wR(F2) = 0.071H-atom parameters constrained
S = 1.04Δρmax = 0.18 e Å3
1623 reflectionsΔρmin = 0.14 e Å3
174 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
N10.35428 (16)0.22736 (6)0.2232 (2)0.0248 (3)
C20.31867 (18)0.27099 (7)0.3359 (2)0.0250 (3)
C30.36758 (18)0.32872 (6)0.2826 (2)0.0241 (3)
C40.43857 (18)0.31670 (7)0.1635 (2)0.0240 (3)
N50.44486 (16)0.25431 (6)0.1332 (2)0.0239 (2)
C60.37458 (19)0.16362 (7)0.2688 (2)0.0245 (3)
C70.2491 (2)0.13330 (7)0.2930 (3)0.0305 (3)
H70.15170.15500.27820.037*
C80.2679 (3)0.07098 (8)0.3392 (3)0.0386 (4)
H80.18460.05030.36020.046*
C90.4070 (3)0.03872 (8)0.3550 (3)0.0420 (4)
H90.41810.00400.38520.050*
C100.5303 (2)0.06878 (8)0.3266 (3)0.0373 (4)
H100.62460.04650.33510.045*
C110.5156 (2)0.13149 (8)0.2858 (3)0.0301 (3)
H110.60120.15240.26960.036*
O120.26349 (16)0.25874 (6)0.45386 (19)0.0330 (3)
N130.35152 (17)0.38830 (6)0.3448 (2)0.0291 (3)
C140.4310 (2)0.43628 (7)0.3067 (3)0.0311 (3)
C150.5584 (2)0.41980 (8)0.2363 (3)0.0328 (3)
H15A0.67070.41000.36210.039*
H15B0.57570.45630.16900.039*
C160.5053 (2)0.36558 (7)0.0828 (3)0.0290 (3)
H16A0.41490.37850.05940.035*
H16B0.60590.35030.07480.035*
C170.3917 (2)0.23369 (8)0.0807 (2)0.0291 (3)
H17A0.27170.24580.17590.044*
H17B0.40180.18890.08210.044*
H17C0.46620.25270.12670.044*
C180.2290 (3)0.40112 (8)0.4156 (3)0.0394 (4)
H18A0.26980.43620.51190.059*
H18B0.21910.36500.48830.059*
H18C0.11590.41070.29420.059*
O190.4061 (2)0.48961 (6)0.3370 (2)0.0423 (3)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0286 (6)0.0233 (6)0.0300 (6)0.0013 (4)0.0203 (5)0.0012 (5)
C20.0246 (6)0.0261 (7)0.0255 (6)0.0001 (5)0.0136 (5)0.0008 (5)
C30.0255 (6)0.0227 (6)0.0252 (7)0.0010 (5)0.0136 (5)0.0018 (5)
C40.0232 (6)0.0254 (7)0.0241 (6)0.0015 (5)0.0124 (5)0.0023 (5)
N50.0259 (5)0.0252 (6)0.0259 (6)0.0023 (4)0.0171 (5)0.0005 (5)
C60.0281 (6)0.0216 (6)0.0244 (6)0.0030 (5)0.0136 (5)0.0020 (5)
C70.0339 (8)0.0282 (8)0.0337 (8)0.0062 (6)0.0203 (6)0.0040 (6)
C80.0523 (10)0.0289 (8)0.0423 (10)0.0126 (7)0.0295 (8)0.0047 (7)
C90.0576 (11)0.0207 (7)0.0462 (10)0.0034 (7)0.0249 (8)0.0007 (7)
C100.0389 (8)0.0272 (8)0.0416 (10)0.0044 (6)0.0173 (7)0.0011 (6)
C110.0272 (7)0.0269 (7)0.0333 (8)0.0022 (5)0.0130 (6)0.0022 (6)
O120.0435 (6)0.0324 (6)0.0363 (6)0.0002 (5)0.0299 (5)0.0015 (5)
N130.0343 (6)0.0240 (6)0.0316 (6)0.0003 (5)0.0185 (5)0.0012 (5)
C140.0378 (8)0.0243 (7)0.0265 (7)0.0023 (6)0.0127 (6)0.0009 (6)
C150.0341 (7)0.0276 (7)0.0346 (8)0.0066 (6)0.0157 (6)0.0040 (6)
C160.0305 (7)0.0293 (7)0.0297 (7)0.0030 (5)0.0170 (6)0.0053 (6)
C170.0277 (7)0.0353 (8)0.0270 (7)0.0014 (6)0.0159 (6)0.0038 (6)
C180.0490 (10)0.0332 (8)0.0491 (10)0.0044 (7)0.0343 (9)0.0036 (7)
O190.0596 (8)0.0229 (6)0.0438 (7)0.0010 (5)0.0255 (6)0.0012 (5)
Geometric parameters (Å, º) top
N1—C21.4009 (19)C10—C111.390 (2)
N1—N51.4098 (16)C10—H100.9500
N1—C61.4173 (18)C11—H110.9500
C2—O121.2269 (18)N13—C141.371 (2)
C2—C31.449 (2)N13—C181.462 (2)
C3—C41.344 (2)C14—O191.224 (2)
C3—N131.4069 (19)C14—C151.517 (3)
C4—N51.3820 (19)C15—C161.536 (2)
C4—C161.485 (2)C15—H15A0.9900
N5—C171.4691 (19)C15—H15B0.9900
C6—C71.392 (2)C16—H16A0.9900
C6—C111.395 (2)C16—H16B0.9900
C7—C81.388 (2)C17—H17A0.9800
C7—H70.9500C17—H17B0.9800
C8—C91.385 (3)C17—H17C0.9800
C8—H80.9500C18—H18A0.9800
C9—C101.389 (3)C18—H18B0.9800
C9—H90.9500C18—H18C0.9800
C2—N1—N5110.78 (12)C6—C11—H11120.2
C2—N1—C6124.29 (12)C14—N13—C3119.08 (13)
N5—N1—C6118.88 (12)C14—N13—C18119.34 (14)
O12—C2—N1124.53 (14)C3—N13—C18120.76 (13)
O12—C2—C3131.78 (14)O19—C14—N13121.55 (16)
N1—C2—C3103.65 (12)O19—C14—C15121.68 (15)
C4—C3—N13123.53 (13)N13—C14—C15116.69 (14)
C4—C3—C2108.44 (13)C14—C15—C16115.22 (13)
N13—C3—C2128.01 (13)C14—C15—H15A108.5
C3—C4—N5111.62 (12)C16—C15—H15A108.5
C3—C4—C16122.80 (14)C14—C15—H15B108.5
N5—C4—C16125.56 (13)C16—C15—H15B108.5
C4—N5—N1104.62 (11)H15A—C15—H15B107.5
C4—N5—C17117.15 (13)C4—C16—C15107.06 (13)
N1—N5—C17115.18 (12)C4—C16—H16A110.3
C7—C6—C11120.43 (14)C15—C16—H16A110.3
C7—C6—N1118.59 (14)C4—C16—H16B110.3
C11—C6—N1120.98 (13)C15—C16—H16B110.3
C8—C7—C6119.23 (16)H16A—C16—H16B108.6
C8—C7—H7120.4N5—C17—H17A109.5
C6—C7—H7120.4N5—C17—H17B109.5
C9—C8—C7120.61 (16)H17A—C17—H17B109.5
C9—C8—H8119.7N5—C17—H17C109.5
C7—C8—H8119.7H17A—C17—H17C109.5
C8—C9—C10120.07 (16)H17B—C17—H17C109.5
C8—C9—H9120.0N13—C18—H18A109.5
C10—C9—H9120.0N13—C18—H18B109.5
C9—C10—C11119.95 (16)H18A—C18—H18B109.5
C9—C10—H10120.0N13—C18—H18C109.5
C11—C10—H10120.0H18A—C18—H18C109.5
C10—C11—C6119.67 (15)H18B—C18—H18C109.5
C10—C11—H11120.2
N5—N1—C2—O12169.21 (15)N5—N1—C6—C1119.2 (2)
C6—N1—C2—O1217.1 (2)C11—C6—C7—C81.5 (2)
N5—N1—C2—C38.97 (15)N1—C6—C7—C8179.53 (16)
C6—N1—C2—C3161.12 (13)C6—C7—C8—C91.9 (3)
O12—C2—C3—C4173.11 (17)C7—C8—C9—C100.7 (3)
N1—C2—C3—C44.88 (15)C8—C9—C10—C111.1 (3)
O12—C2—C3—N135.2 (3)C9—C10—C11—C61.5 (3)
N1—C2—C3—N13176.85 (14)C7—C6—C11—C100.2 (2)
N13—C3—C4—N5177.41 (13)N1—C6—C11—C10178.76 (16)
C2—C3—C4—N50.95 (17)C4—C3—N13—C148.7 (2)
N13—C3—C4—C160.9 (2)C2—C3—N13—C14169.31 (14)
C2—C3—C4—C16179.27 (13)C4—C3—N13—C18160.80 (16)
C3—C4—N5—N16.36 (17)C2—C3—N13—C1821.2 (2)
C16—C4—N5—N1175.38 (13)C3—N13—C14—O19172.06 (16)
C3—C4—N5—C17135.25 (13)C18—N13—C14—O192.4 (2)
C16—C4—N5—C1746.5 (2)C3—N13—C14—C1511.1 (2)
C2—N1—N5—C49.63 (16)C18—N13—C14—C15179.24 (16)
C6—N1—N5—C4163.47 (12)O19—C14—C15—C16143.95 (16)
C2—N1—N5—C17139.69 (13)N13—C14—C15—C1639.2 (2)
C6—N1—N5—C1766.46 (18)C3—C4—C16—C1526.93 (19)
C2—N1—C6—C750.1 (2)N5—C4—C16—C15151.14 (15)
N5—N1—C6—C7159.82 (13)C14—C15—C16—C444.36 (18)
C2—N1—C6—C11130.91 (15)

Experimental details

Crystal data
Chemical formulaC14H15N3O2
Mr257.29
Crystal system, space groupMonoclinic, Cc
Temperature (K)193
a, b, c (Å)8.9721 (7), 21.7653 (19), 7.3725 (5)
β (°) 120.214 (5)
V3)1244.12 (17)
Z4
Radiation typeMo Kα
µ (mm1)0.10
Crystal size (mm)0.45 × 0.17 × 0.16
Data collection
DiffractometerStoe IPDS 2T
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
4103, 1623, 1541
Rint0.036
(sin θ/λ)max1)0.680
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.027, 0.071, 1.04
No. of reflections1623
No. of parameters174
No. of restraints2
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.18, 0.14

Computer programs: X-AREA (Stoe, 2010), X-RED (Stoe, 2010), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2009).

 

References

First citationAltomare, A., Burla, M. C., Camalli, M., Cascarano, G. L., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G., Polidori, G. & Spagna, R. (1999). J. Appl. Cryst. 32, 115–119.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationGreene, T. W. & Wuts, P. G. M. (1999). Protective Groups in Organic Synthesis, Vol. 3. New York: John Wiley & Sons, Inc.  Google Scholar
First citationPierre, S. C., Schmidt, R., Brenneis, C., Michaelis, M., Geisslinger, G. & Scholich, K. (2007). Br. J. Pharmacol. 151, 494–503.  Web of Science CrossRef PubMed CAS Google Scholar
First citationSakaitani, M., Hori, K. & Ohfune, Y. (1988). Tetrahedron Lett. 29, 2983–2984.  CrossRef CAS Web of Science 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. (2009). Acta Cryst. D65, 148–155.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationStoe (2010). X-AREA and X-RED. Stoe & Cie GmbH, Darmstadt, Germany.  Google Scholar

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