2-(3,4,5-Trimethoxy­phen­yl)-1H-pyrrolo[2,3-b]pyridine

Selig, R.; Schollmeyer, D.; Albrecht, W.; Laufer, S.

doi:10.1107/S1600536809047540

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 65| Part 12| December 2009| Page o3097

doi:10.1107/S1600536809047540

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2-(3,4,5-Trimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridine

Roland Selig,^a Dieter Schollmeyer,^b Wolfgang Albrecht ^c and Stefan Laufer ^a ^*

^aEberhard-Karls-University Tuebingen, Auf der Morgenstelle 8, 72076 Tuebingen, Germany, ^bUniversity Mainz, Duesbergweg 10-14, 55099 Mainz, Germany, and ^cc-a-i-r biosciences GmbH, Paul-Ehrlich-Strasse 15, 72076 Tuebingen, Germany
^*Correspondence e-mail: stefan.laufer@uni-tuebingen.de

(Received 2 November 2009; accepted 10 November 2009; online 14 November 2009)

In the title compound, C₁₆H₁₆N₂O₃, the 3,4,5-trimethoxyphenyl group makes a dihedral angle of 10.04 (7)° toward the 1H-pyrrolo[2,3-b]pyridine system. The crystal structure displays intermolecular N—H⋯N hydrogen bonds, forming inversion dimers.

Related literature

For the synthesis of the title copmpound, see: Davis et al. (1992 )

Experimental

Crystal data

C₁₆H₁₆N₂O₃
M_r = 284.31
Monoclinic, P 2₁ /c
a = 7.6283 (9) Å
b = 10.1745 (4) Å
c = 18.604 (2) Å
β = 104.778 (6)°
V = 1396.2 (2) Å³
Z = 4
Cu Kα radiation
μ = 0.78 mm⁻¹
T = 193 K
0.40 × 0.40 × 0.25 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: none
2865 measured reflections
2657 independent reflections
2352 reflections with I > 2σ(I)
R_int = 0.020
3 standard reflections frequency: 60 min intensity decay: 2%

Refinement

R[F² > 2σ(F²)] = 0.045
wR(F²) = 0.125
S = 1.07
2657 reflections
193 parameters
H-atom parameters constrained
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯N7ⁱ	0.95	2.12	3.061 (2)	171
Symmetry code: (i) -x+1, -y+1, -z+1.

Data collection: CAD-4 Software (Enraf–Nonius, 1989 ); cell refinement: CAD-4 Software; data reduction: CORINC (Dräger & Gattow, 1971 ); 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.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809047540/im2158sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809047540/im2158Isup2.hkl

checkCIF report

Comment top

7-Azaindoles are found in natural and synthetic compounds of biological interest. The interest in 7-azaindoles as indole analogues has arisen in recent years due to their improved physicochemical and pharmacological properties. The substitution of this heterocycle is widely studied and used in synthesis of many compounds of potential pharmaceutical interest. The 3,4,5-trimethoxyphenyl moiety encloses a dihedral angle of 10.04 (7)° toward the 1H-pyrrolo[2,3-b]pyridine system. The crystal structure of 2-(3,4,5-trimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridine, C₁₆H₁₆N₂O₃, is characterized by an intermolecular hydrogen bond N1–H1···N7 (2.12 Å).

Related literature top

For the synthesis of the title copmpound, see: Davis et al. (1992)

Experimental top

3-Methylpyridine (0.68 g 7.25 mmol) was added dropwise to a freshly prepared solution of LDA in THF (2M) (3.6 ml 7.25 mmol) at 273 K. The resulting suspension was stirred at 273 K for 30 min. Trimethoxybenzonitrile (1.4 g 7.25 mmol) was added dropwise at such a rate that the temperature did not rise above 283 K. Stirring was continued for 60 min. at 273 K. Another portion of LDA solution (3.6 ml 7.25 mmol) was added and stirring was continued for 10 h at 353 K. The final reaction mixture was allowed to cool and ice-water was added. The mixture was extracted with ethylacetate and the combined extracts were dried (Na₂SO₄) and the solvent was evaporated under reduced pressure. The residue was subjected to flash chromatography. The title compound was obtained in a yield of 67% (1.37 g 4.83 mmol). Crystals suitable for X-ray diffraction were obtained by slow evaporation of the solvent (methanol) during several weeks.

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: 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

Fig. 1. View of compound I. Displacement ellipsoids are drawn at the 50% probability level.

2-(3,4,5-Trimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridine top

Crystal data top

C₁₆H₁₆N₂O₃	F(000) = 600
M_r = 284.31	D_x = 1.353 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ybc	Cell parameters from 25 reflections
a = 7.6283 (9) Å	θ = 66–70°
b = 10.1745 (4) Å	µ = 0.78 mm⁻¹
c = 18.604 (2) Å	T = 193 K
β = 104.778 (6)°	Plate, colourless
V = 1396.2 (2) Å³	0.40 × 0.40 × 0.25 mm
Z = 4

Data collection top

Enraf–Nonius CAD-4 diffractometer	R_int = 0.020
Radiation source: rotating anode	θ_max = 70.0°, θ_min = 4.9°
Graphite monochromator	h = −9→0
ω/2θ scans	k = 0→12
2865 measured reflections	l = −21→22
2657 independent reflections	3 standard reflections every 60 min
2352 reflections with I > 2σ(I)	intensity decay: 2%

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)] = 0.045	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.125	H-atom parameters constrained
S = 1.07	w = 1/[σ²(F_o²) + (0.0641P)² + 0.5259P] where P = (F_o² + 2F_c²)/3
2657 reflections	(Δ/σ)_max < 0.001
193 parameters	Δρ_max = 0.20 e Å⁻³
0 restraints	Δρ_min = −0.21 e Å⁻³

Crystal data top

C₁₆H₁₆N₂O₃	V = 1396.2 (2) Å³
M_r = 284.31	Z = 4
Monoclinic, P2₁/c	Cu Kα radiation
a = 7.6283 (9) Å	µ = 0.78 mm⁻¹
b = 10.1745 (4) Å	T = 193 K
c = 18.604 (2) Å	0.40 × 0.40 × 0.25 mm
β = 104.778 (6)°

Data collection top

Enraf–Nonius CAD-4 diffractometer	R_int = 0.020
2865 measured reflections	3 standard reflections every 60 min
2657 independent reflections	intensity decay: 2%
2352 reflections with I > 2σ(I)

Refinement top

R[F² > 2σ(F²)] = 0.045	0 restraints
wR(F²) = 0.125	H-atom parameters constrained
S = 1.07	Δρ_max = 0.20 e Å⁻³
2657 reflections	Δρ_min = −0.21 e Å⁻³
193 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
N1	0.62152 (18)	0.53967 (13)	0.42466 (7)	0.0312 (3)
H1	0.6399	0.4802	0.4653	0.037*
C2	0.7269 (2)	0.55266 (16)	0.37403 (8)	0.0308 (3)
C3	0.6670 (2)	0.65831 (17)	0.32906 (9)	0.0360 (4)
H3	0.7158	0.6888	0.2899	0.043*
C3A	0.5187 (2)	0.71430 (17)	0.35131 (9)	0.0344 (4)
C4	0.4017 (3)	0.82022 (19)	0.32915 (10)	0.0451 (4)
H4	0.4120	0.8762	0.2896	0.054*
C5	0.2705 (3)	0.8406 (2)	0.36686 (11)	0.0524 (5)
H5	0.1888	0.9123	0.3536	0.063*
C6	0.2568 (3)	0.7568 (2)	0.42413 (11)	0.0492 (5)
H6	0.1629	0.7736	0.4481	0.059*
N7	0.3663 (2)	0.65397 (15)	0.44823 (8)	0.0381 (4)
C7A	0.4931 (2)	0.63661 (16)	0.41105 (9)	0.0310 (3)
C8	0.8710 (2)	0.45896 (16)	0.37109 (8)	0.0307 (3)
C9	0.9838 (2)	0.48432 (16)	0.32401 (9)	0.0330 (4)
H9	0.9711	0.5640	0.2966	0.040*
C10	1.1137 (2)	0.39363 (17)	0.31741 (9)	0.0324 (4)
C11	1.1358 (2)	0.27617 (16)	0.35828 (9)	0.0313 (3)
C12	1.0243 (2)	0.25251 (16)	0.40535 (9)	0.0326 (4)
C13	0.8925 (2)	0.34277 (16)	0.41142 (9)	0.0338 (4)
H13	0.8164	0.3249	0.4435	0.041*
O14	1.22631 (17)	0.40749 (13)	0.27123 (7)	0.0439 (3)
C15	1.1984 (3)	0.5172 (2)	0.22231 (10)	0.0454 (5)
H15A	1.0720	0.5186	0.1929	0.068*
H15B	1.2787	0.5103	0.1889	0.068*
H15C	1.2253	0.5984	0.2513	0.068*
O16	1.25139 (16)	0.17927 (12)	0.34718 (7)	0.0376 (3)
C17	1.4407 (2)	0.2090 (2)	0.37068 (11)	0.0458 (4)
H17A	1.4722	0.2711	0.3357	0.069*
H17B	1.5110	0.1281	0.3721	0.069*
H17C	1.4684	0.2484	0.4204	0.069*
O18	1.03203 (16)	0.13515 (12)	0.44277 (7)	0.0399 (3)
C19	1.1896 (3)	0.1164 (2)	0.50170 (11)	0.0518 (5)
H19A	1.2953	0.1062	0.4813	0.078*
H19B	1.1753	0.0372	0.5297	0.078*
H19C	1.2073	0.1928	0.5349	0.078*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0357 (7)	0.0303 (7)	0.0307 (7)	0.0044 (5)	0.0140 (5)	0.0038 (5)
C2	0.0334 (8)	0.0312 (8)	0.0295 (7)	−0.0014 (6)	0.0112 (6)	−0.0015 (6)
C3	0.0419 (9)	0.0371 (9)	0.0310 (8)	0.0024 (7)	0.0134 (7)	0.0049 (7)
C3A	0.0397 (9)	0.0348 (8)	0.0283 (8)	0.0025 (7)	0.0082 (6)	0.0019 (6)
C4	0.0566 (11)	0.0429 (10)	0.0369 (9)	0.0136 (9)	0.0135 (8)	0.0129 (8)
C5	0.0596 (12)	0.0519 (12)	0.0470 (10)	0.0276 (10)	0.0161 (9)	0.0138 (9)
C6	0.0513 (11)	0.0563 (12)	0.0445 (10)	0.0241 (9)	0.0203 (8)	0.0092 (9)
N7	0.0427 (8)	0.0400 (8)	0.0345 (7)	0.0116 (6)	0.0149 (6)	0.0044 (6)
C7A	0.0346 (8)	0.0298 (8)	0.0281 (7)	0.0025 (6)	0.0072 (6)	−0.0008 (6)
C8	0.0328 (8)	0.0304 (8)	0.0301 (7)	−0.0012 (6)	0.0101 (6)	−0.0018 (6)
C9	0.0383 (8)	0.0310 (8)	0.0317 (8)	−0.0001 (7)	0.0127 (7)	0.0024 (6)
C10	0.0358 (8)	0.0356 (9)	0.0289 (7)	−0.0028 (7)	0.0138 (6)	−0.0018 (6)
C11	0.0334 (8)	0.0300 (8)	0.0318 (8)	0.0003 (6)	0.0104 (6)	−0.0045 (6)
C12	0.0361 (8)	0.0287 (8)	0.0339 (8)	−0.0024 (6)	0.0109 (6)	0.0016 (6)
C13	0.0347 (8)	0.0360 (9)	0.0346 (8)	−0.0002 (7)	0.0162 (7)	0.0027 (7)
O14	0.0502 (7)	0.0475 (8)	0.0431 (7)	0.0089 (6)	0.0285 (6)	0.0092 (6)
C15	0.0417 (9)	0.0565 (12)	0.0424 (10)	−0.0042 (8)	0.0184 (8)	0.0123 (8)
O16	0.0388 (6)	0.0343 (6)	0.0422 (6)	0.0041 (5)	0.0148 (5)	−0.0042 (5)
C17	0.0393 (10)	0.0520 (11)	0.0466 (10)	0.0033 (8)	0.0121 (8)	−0.0037 (9)
O18	0.0414 (7)	0.0327 (6)	0.0457 (7)	−0.0015 (5)	0.0113 (5)	0.0095 (5)
C19	0.0540 (12)	0.0544 (12)	0.0426 (10)	−0.0083 (9)	0.0041 (9)	0.0139 (9)

Geometric parameters (Å, º) top

N1—C7A	1.367 (2)	C10—O14	1.3681 (19)
N1—C2	1.3917 (19)	C10—C11	1.403 (2)
N1—H1	0.9499	C11—O16	1.3729 (19)
C2—C3	1.367 (2)	C11—C12	1.389 (2)
C2—C8	1.467 (2)	C12—O18	1.3758 (19)
C3—C3A	1.419 (2)	C12—C13	1.387 (2)
C3—H3	0.9500	C13—H13	0.9500
C3A—C4	1.393 (2)	O14—C15	1.422 (2)
C3A—C7A	1.417 (2)	C15—H15A	0.9800
C4—C5	1.377 (3)	C15—H15B	0.9800
C4—H4	0.9500	C15—H15C	0.9800
C5—C6	1.389 (3)	O16—C17	1.430 (2)
C5—H5	0.9500	C17—H17A	0.9800
C6—N7	1.343 (2)	C17—H17B	0.9800
C6—H6	0.9500	C17—H17C	0.9800
N7—C7A	1.336 (2)	O18—C19	1.418 (2)
C8—C13	1.387 (2)	C19—H19A	0.9800
C8—C9	1.400 (2)	C19—H19B	0.9800
C9—C10	1.382 (2)	C19—H19C	0.9800
C9—H9	0.9500

C7A—N1—C2	108.43 (13)	O14—C10—C11	114.85 (14)
C7A—N1—H1	124.1	C9—C10—C11	120.66 (14)
C2—N1—H1	127.2	O16—C11—C12	119.38 (15)
C3—C2—N1	109.17 (14)	O16—C11—C10	121.53 (14)
C3—C2—C8	128.68 (14)	C12—C11—C10	118.76 (14)
N1—C2—C8	122.09 (14)	O18—C12—C13	118.16 (14)
C2—C3—C3A	107.69 (14)	O18—C12—C11	121.02 (14)
C2—C3—H3	126.2	C13—C12—C11	120.64 (15)
C3A—C3—H3	126.2	C12—C13—C8	120.57 (14)
C4—C3A—C7A	117.21 (16)	C12—C13—H13	119.7
C4—C3A—C3	136.27 (16)	C8—C13—H13	119.7
C7A—C3A—C3	106.52 (14)	C10—O14—C15	117.87 (13)
C5—C4—C3A	117.38 (16)	O14—C15—H15A	109.5
C5—C4—H4	121.3	O14—C15—H15B	109.5
C3A—C4—H4	121.3	H15A—C15—H15B	109.5
C4—C5—C6	120.36 (17)	O14—C15—H15C	109.5
C4—C5—H5	119.8	H15A—C15—H15C	109.5
C6—C5—H5	119.8	H15B—C15—H15C	109.5
N7—C6—C5	124.90 (17)	C11—O16—C17	116.03 (13)
N7—C6—H6	117.5	O16—C17—H17A	109.5
C5—C6—H6	117.6	O16—C17—H17B	109.5
C7A—N7—C6	113.64 (15)	H17A—C17—H17B	109.5
N7—C7A—N1	125.32 (14)	O16—C17—H17C	109.5
N7—C7A—C3A	126.50 (15)	H17A—C17—H17C	109.5
N1—C7A—C3A	108.18 (14)	H17B—C17—H17C	109.5
C13—C8—C9	119.24 (15)	C12—O18—C19	115.25 (14)
C13—C8—C2	121.36 (14)	O18—C19—H19A	109.5
C9—C8—C2	119.33 (14)	O18—C19—H19B	109.5
C10—C9—C8	120.12 (15)	H19A—C19—H19B	109.5
C10—C9—H9	119.9	O18—C19—H19C	109.5
C8—C9—H9	119.9	H19A—C19—H19C	109.5
O14—C10—C9	124.47 (15)	H19B—C19—H19C	109.5

C7A—N1—C2—C3	0.71 (18)	C13—C8—C9—C10	0.7 (2)
C7A—N1—C2—C8	−176.55 (14)	C2—C8—C9—C10	−176.40 (14)
N1—C2—C3—C3A	−0.21 (19)	C8—C9—C10—O14	177.84 (15)
C8—C2—C3—C3A	176.82 (16)	C8—C9—C10—C11	−0.8 (2)
C2—C3—C3A—C4	179.8 (2)	O14—C10—C11—O16	−5.2 (2)
C2—C3—C3A—C7A	−0.35 (19)	C9—C10—C11—O16	173.52 (14)
C7A—C3A—C4—C5	−0.2 (3)	O14—C10—C11—C12	−178.56 (14)
C3—C3A—C4—C5	179.6 (2)	C9—C10—C11—C12	0.2 (2)
C3A—C4—C5—C6	−0.6 (3)	O16—C11—C12—O18	2.1 (2)
C4—C5—C6—N7	1.1 (4)	C10—C11—C12—O18	175.55 (14)
C5—C6—N7—C7A	−0.7 (3)	O16—C11—C12—C13	−172.96 (15)
C6—N7—C7A—N1	179.77 (17)	C10—C11—C12—C13	0.5 (2)
C6—N7—C7A—C3A	−0.1 (3)	O18—C12—C13—C8	−175.80 (14)
C2—N1—C7A—N7	179.17 (15)	C11—C12—C13—C8	−0.6 (2)
C2—N1—C7A—C3A	−0.92 (18)	C9—C8—C13—C12	0.0 (2)
C4—C3A—C7A—N7	0.6 (3)	C2—C8—C13—C12	177.04 (15)
C3—C3A—C7A—N7	−179.31 (16)	C9—C10—O14—C15	−5.3 (2)
C4—C3A—C7A—N1	−179.33 (15)	C11—C10—O14—C15	173.38 (15)
C3—C3A—C7A—N1	0.79 (18)	C12—C11—O16—C17	−117.52 (17)
C3—C2—C8—C13	−167.47 (17)	C10—C11—O16—C17	69.2 (2)
N1—C2—C8—C13	9.2 (2)	C13—C12—O18—C19	−113.18 (18)
C3—C2—C8—C9	9.5 (3)	C11—C12—O18—C19	71.7 (2)
N1—C2—C8—C9	−173.77 (14)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···N7ⁱ	0.95	2.12	3.061 (2)	171

Symmetry code: (i) −x+1, −y+1, −z+1.

Experimental details

Crystal data
Chemical formula	C₁₆H₁₆N₂O₃
M_r	284.31
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	193
a, b, c (Å)	7.6283 (9), 10.1745 (4), 18.604 (2)
β (°)	104.778 (6)
V (Å³)	1396.2 (2)
Z	4
Radiation type	Cu Kα
µ (mm⁻¹)	0.78
Crystal size (mm)	0.40 × 0.40 × 0.25

Data collection
Diffractometer	Enraf–Nonius CAD-4 diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	2865, 2657, 2352
R_int	0.020
(sin θ/λ)_max (Å⁻¹)	0.609

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.045, 0.125, 1.07
No. of reflections	2657
No. of parameters	193
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.20, −0.21

Computer programs: CAD-4 Software (Enraf–Nonius, 1989), CORINC (Dräger & Gattow, 1971), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···N7ⁱ	0.95	2.12	3.061 (2)	171

Symmetry code: (i) −x+1, −y+1, −z+1.

Acknowledgements

The authors would like to thank the Federal Ministry of Education and Research, Germany, Merckle GmbH, Ulm, Germany, and the Fonds der Chemischen Industrie, Germany, for their generous support of this work.

References

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