4-Chloro-7-methoxy­methyl-2-phenyl-7H-pyrrolo[2,3-b]pyridine

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

doi:10.1107/S1600536810008822

organic compounds

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ISSN: 2056-9890

Volume 66| Part 4| April 2010| Page o822

doi:10.1107/S1600536810008822

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4-Chloro-7-methoxymethyl-2-phenyl-7H-pyrrolo[2,3-b]pyridine

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

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

(Received 8 March 2010; accepted 8 March 2010; online 13 March 2010)

In the title compound, C₁₅H₁₃ClN₂O, the phenyl group makes a dihedral angle of 7.91 (8)° with the pyrrole ring. The crystal structure forms a three-dimensional network stabilized by π–π interactions [centroid–centroid distances = 3.807 (1) Å] between the pyridine and phenyl rings and via intermolecular C—H⋯O hydrogen bonds.

Related literature

Chlorination of 2-phenyl-1H-pyrrolo[2,3-b]pyridine was performed by an analogous procedure, see: Layek et al. (2009 ).

Experimental

Crystal data

C₁₅H₁₃ClN₂O
M_r = 272.72
Orthorhombic, P 2₁ 2₁ 2₁
a = 8.4785 (8) Å
b = 9.6576 (10) Å
c = 15.8560 (16) Å
V = 1298.3 (2) Å³
Z = 4
Mo Kα radiation
μ = 0.29 mm⁻¹
T = 173 K
0.32 × 0.21 × 0.08 mm

Data collection

Bruker SMART APEXII diffractometer
5977 measured reflections
3084 independent reflections
2667 reflections with I > 2σ(I)
R_int = 0.028

Refinement

R[F² > 2σ(F²)] = 0.037
wR(F²) = 0.079
S = 1.03
3084 reflections
173 parameters
H-atom parameters constrained
Δρ_max = 0.21 e Å⁻³
Δρ_min = −0.22 e Å⁻³
Absolute structure: Flack (1983 ), 1299 Friedel pairs
Flack parameter: 0.02 (6)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C5—H5⋯O15ⁱ	0.95	2.32	3.237 (2)	162
Symmetry code: (i) $[-x+1, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]$ .

Data collection: APEX2 (Bruker, 2006 ); cell refinement: SAINT (Bruker, 2006); data reduction: SAINT; 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/S1600536810008822/bt5211sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536810008822/bt5211Isup2.hkl

checkCIF report

Comment top

N-protection of 7-azaindoles is a often used and necessary procedure for further NH sensitive reactions. Many protecting procedures with 4-chloro-1H-pyrrolo[2,3-b]pyridine are kown in literature. By N-protection of 4-chloro-2-phenyl-1H-pyrrolo[2,3-b]pyridine with methoxymethylchloride, two regioisomeres are formed, the expected 4-chloro-1-(methoxymethyl)-2-phenyl-1H-pyrrolo[2,3-b]pyridine and the title compound in a ratio of 1:1.6. The title compound and its regioisomer demonstrate the delocalization of the deprotonated anionic 4-chloro-1-(methoxymethyl)-2-phenyl-1H-pyrrolo[2,3-b]pyridine species. The phenyl moiety encloses a dihedral angle of 7.91 (8)° toward the azaindole system. The crystal structure is characterized by intermolecular hydrogen bond C5—H5···O15 (2.32 Å) and intramolecular hydrogen interactions C13—H13···N1 (2.54 Å), C14—H14B···N1 (2.48°). Stabilization of the three dimensional network is performed by π -π interactions between the pyridine and the phenyl rings with centroid distances of 3.807 (1) Å (symmetry operator 1.5-x, 1-y, -0.5∓z).

Related literature top

Chlorination of 2-phenyl-1H-pyrrolo[2,3-b]pyridine was performed by an analogous procedure, see: Layek et al. (2009).

Experimental top

2,5 g (11 mmol) 4-chloro-1-(methoxymethyl)-2-phenyl-1H-pyrrolo[2,3-b]pyridine was dissolved in dry THF (15 ml). After addition of 0.61 g (15 mmol) NaH (60% in mineral oil) the reaction mixture was stirred for 15 minutes at room temperature. 7.3 ml (15 mmol) methoxymethylchloride (2.1M in toluene) was added and the mixture was stirred for further 15 minutes. The reaction mixture was quenched with concentrated aqueous ammonium chloride solution. After extraction with ethyl acetate, the crude product was purified by flash chromatography. Crystals suitable for X-ray analysis were obtained by slow crystallisation from methanol.

Computing details top

Data collection: APEX2 (Bruker, 2006); cell refinement: SAINT (Bruker, 2006); data reduction: SAINT (Bruker, 2006); 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.

4-Chloro-7-methoxymethyl-2-phenyl-7H-pyrrolo[2,3-b]pyridine top

Crystal data top

C₁₅H₁₃ClN₂O	F(000) = 568
M_r = 272.72	D_x = 1.395 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 1903 reflections
a = 8.4785 (8) Å	θ = 2.5–26.5°
b = 9.6576 (10) Å	µ = 0.29 mm⁻¹
c = 15.8560 (16) Å	T = 173 K
V = 1298.3 (2) Å³	Block, yellow
Z = 4	0.32 × 0.21 × 0.08 mm

Data collection top

Bruker SMART APEXII diffractometer	2667 reflections with I > 2σ(I)
Radiation source: sealed tube	R_int = 0.028
Graphite monochromator	θ_max = 27.9°, θ_min = 2.5°
CCD scan	h = −11→9
5977 measured reflections	k = −11→12
3084 independent reflections	l = −18→20

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.037	H-atom parameters constrained
wR(F²) = 0.079	w = 1/[σ²(F_o²) + (0.0335P)² + 0.0915P] where P = (F_o² + 2F_c²)/3
S = 1.03	(Δ/σ)_max < 0.001
3084 reflections	Δρ_max = 0.21 e Å⁻³
173 parameters	Δρ_min = −0.22 e Å⁻³
0 restraints	Absolute structure: Flack (1983), 1294 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.02 (6)

Crystal data top

C₁₅H₁₃ClN₂O	V = 1298.3 (2) Å³
M_r = 272.72	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 8.4785 (8) Å	µ = 0.29 mm⁻¹
b = 9.6576 (10) Å	T = 173 K
c = 15.8560 (16) Å	0.32 × 0.21 × 0.08 mm

Data collection top

Bruker SMART APEXII diffractometer	2667 reflections with I > 2σ(I)
5977 measured reflections	R_int = 0.028
3084 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.037	H-atom parameters constrained
wR(F²) = 0.079	Δρ_max = 0.21 e Å⁻³
S = 1.03	Δρ_min = −0.22 e Å⁻³
3084 reflections	Absolute structure: Flack (1983), 1294 Friedel pairs
173 parameters	Absolute structure parameter: 0.02 (6)
0 restraints

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.

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
Cl1	0.29645 (6)	0.30454 (5)	0.60634 (3)	0.03778 (14)
N1	0.64025 (18)	0.65066 (16)	0.45780 (9)	0.0247 (3)
C2	0.5784 (2)	0.55036 (19)	0.40408 (11)	0.0237 (4)
C3	0.4866 (2)	0.4524 (2)	0.44513 (11)	0.0258 (4)
H3	0.4352	0.3746	0.4208	0.031*
C3A	0.4856 (2)	0.4927 (2)	0.53056 (11)	0.0245 (4)
C4	0.4173 (2)	0.44943 (18)	0.60500 (12)	0.0270 (4)
C5	0.4472 (2)	0.5205 (2)	0.68003 (11)	0.0300 (4)
H5	0.3997	0.4909	0.7312	0.036*
C6	0.5454 (2)	0.6330 (2)	0.67921 (11)	0.0299 (4)
H6	0.5669	0.6793	0.7308	0.036*
N7	0.61298 (17)	0.68081 (16)	0.60720 (9)	0.0263 (3)
C7A	0.5837 (2)	0.61451 (19)	0.53258 (11)	0.0242 (4)
C8	0.6076 (2)	0.56108 (19)	0.31251 (10)	0.0246 (4)
C9	0.5316 (2)	0.4728 (2)	0.25586 (13)	0.0328 (5)
H9	0.4647	0.4017	0.2767	0.039*
C10	0.5525 (3)	0.4874 (2)	0.16978 (12)	0.0367 (5)
H10	0.4995	0.4268	0.1321	0.044*
C11	0.6500 (3)	0.5900 (2)	0.13843 (12)	0.0349 (5)
H11	0.6630	0.6008	0.0793	0.042*
C12	0.7285 (2)	0.6765 (2)	0.19367 (12)	0.0329 (5)
H12	0.7980	0.7453	0.1725	0.040*
C13	0.7061 (2)	0.6632 (2)	0.28038 (11)	0.0289 (4)
H13	0.7587	0.7245	0.3178	0.035*
C14	0.7186 (2)	0.8020 (2)	0.61091 (11)	0.0305 (4)
H14A	0.8005	0.7861	0.6544	0.037*
H14B	0.7723	0.8131	0.5559	0.037*
O15	0.63663 (17)	0.92266 (14)	0.62990 (7)	0.0332 (3)
C16	0.5440 (3)	0.9729 (2)	0.56147 (14)	0.0435 (6)
H16A	0.4921	1.0594	0.5781	0.065*
H16B	0.4640	0.9039	0.5466	0.065*
H16C	0.6123	0.9901	0.5127	0.065*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0405 (3)	0.0307 (2)	0.0422 (3)	−0.0039 (2)	0.0068 (2)	0.0094 (2)
N1	0.0236 (8)	0.0267 (8)	0.0239 (8)	−0.0023 (7)	0.0015 (6)	−0.0018 (6)
C2	0.0219 (9)	0.0252 (9)	0.0241 (8)	0.0029 (8)	−0.0003 (7)	−0.0015 (7)
C3	0.0272 (10)	0.0230 (9)	0.0272 (9)	0.0013 (8)	−0.0015 (7)	−0.0004 (7)
C3A	0.0233 (9)	0.0239 (9)	0.0262 (9)	0.0038 (8)	−0.0022 (7)	0.0026 (7)
C4	0.0257 (9)	0.0239 (9)	0.0313 (9)	0.0040 (8)	0.0024 (8)	0.0059 (8)
C5	0.0341 (11)	0.0309 (11)	0.0251 (10)	0.0071 (9)	0.0047 (8)	0.0063 (8)
C6	0.0337 (11)	0.0344 (11)	0.0215 (9)	0.0066 (9)	−0.0002 (8)	−0.0019 (7)
N7	0.0258 (8)	0.0294 (8)	0.0237 (7)	0.0014 (7)	−0.0018 (6)	−0.0014 (7)
C7A	0.0222 (9)	0.0261 (9)	0.0242 (9)	0.0026 (8)	−0.0022 (7)	0.0000 (7)
C8	0.0242 (10)	0.0260 (10)	0.0238 (8)	0.0052 (8)	0.0013 (7)	−0.0008 (7)
C9	0.0377 (12)	0.0317 (11)	0.0290 (10)	−0.0023 (9)	0.0015 (8)	0.0001 (8)
C10	0.0430 (13)	0.0395 (12)	0.0276 (10)	0.0049 (11)	−0.0036 (8)	−0.0056 (8)
C11	0.0397 (12)	0.0418 (12)	0.0233 (9)	0.0141 (10)	0.0025 (8)	0.0027 (8)
C12	0.0301 (11)	0.0364 (11)	0.0323 (10)	0.0053 (10)	0.0070 (8)	0.0084 (8)
C13	0.0259 (10)	0.0311 (10)	0.0297 (9)	0.0020 (9)	0.0013 (8)	−0.0005 (7)
C14	0.0276 (10)	0.0328 (9)	0.0311 (9)	−0.0026 (10)	−0.0024 (8)	−0.0067 (9)
O15	0.0412 (8)	0.0321 (7)	0.0263 (7)	0.0032 (7)	0.0014 (5)	−0.0073 (5)
C16	0.0458 (14)	0.0366 (13)	0.0480 (13)	0.0034 (12)	−0.0096 (10)	0.0018 (10)

Geometric parameters (Å, º) top

Cl1—C4	1.7345 (19)	C8—C9	1.396 (3)
N1—C7A	1.326 (2)	C9—C10	1.383 (3)
N1—C2	1.393 (2)	C9—H9	0.9500
C2—C3	1.387 (3)	C10—C11	1.383 (3)
C2—C8	1.476 (2)	C10—H10	0.9500
C3—C3A	1.409 (2)	C11—C12	1.381 (3)
C3—H3	0.9500	C11—H11	0.9500
C3A—C4	1.379 (3)	C12—C13	1.394 (3)
C3A—C7A	1.441 (3)	C12—H12	0.9500
C4—C5	1.396 (3)	C13—H13	0.9500
C5—C6	1.369 (3)	C14—O15	1.390 (2)
C5—H5	0.9500	C14—H14A	0.9900
C6—N7	1.358 (2)	C14—H14B	0.9900
C6—H6	0.9500	O15—C16	1.425 (2)
N7—C7A	1.368 (2)	C16—H16A	0.9800
N7—C14	1.475 (2)	C16—H16B	0.9800
C8—C13	1.389 (3)	C16—H16C	0.9800

C7A—N1—C2	103.15 (15)	C10—C9—C8	120.91 (19)
C3—C2—N1	113.49 (16)	C10—C9—H9	119.5
C3—C2—C8	127.11 (16)	C8—C9—H9	119.5
N1—C2—C8	119.31 (16)	C11—C10—C9	120.27 (19)
C2—C3—C3A	105.44 (16)	C11—C10—H10	119.9
C2—C3—H3	127.3	C9—C10—H10	119.9
C3A—C3—H3	127.3	C12—C11—C10	119.57 (18)
C4—C3A—C3	137.84 (18)	C12—C11—H11	120.2
C4—C3A—C7A	118.06 (16)	C10—C11—H11	120.2
C3—C3A—C7A	104.08 (15)	C11—C12—C13	120.28 (19)
C3A—C4—C5	120.28 (17)	C11—C12—H12	119.9
C3A—C4—Cl1	120.18 (14)	C13—C12—H12	119.9
C5—C4—Cl1	119.54 (14)	C8—C13—C12	120.59 (17)
C6—C5—C4	119.48 (17)	C8—C13—H13	119.7
C6—C5—H5	120.3	C12—C13—H13	119.7
C4—C5—H5	120.3	O15—C14—N7	111.71 (14)
N7—C6—C5	122.29 (17)	O15—C14—H14A	109.3
N7—C6—H6	118.9	N7—C14—H14A	109.3
C5—C6—H6	118.9	O15—C14—H14B	109.3
C6—N7—C7A	119.43 (16)	N7—C14—H14B	109.3
C6—N7—C14	119.50 (15)	H14A—C14—H14B	107.9
C7A—N7—C14	121.07 (15)	C14—O15—C16	113.35 (14)
N1—C7A—N7	125.76 (17)	O15—C16—H16A	109.5
N1—C7A—C3A	113.83 (15)	O15—C16—H16B	109.5
N7—C7A—C3A	120.40 (15)	H16A—C16—H16B	109.5
C13—C8—C9	118.36 (17)	O15—C16—H16C	109.5
C13—C8—C2	120.75 (16)	H16A—C16—H16C	109.5
C9—C8—C2	120.84 (17)	H16B—C16—H16C	109.5

C7A—N1—C2—C3	−0.8 (2)	C14—N7—C7A—C3A	177.31 (16)
C7A—N1—C2—C8	176.10 (15)	C4—C3A—C7A—N1	−178.06 (17)
N1—C2—C3—C3A	1.3 (2)	C3—C3A—C7A—N1	0.7 (2)
C8—C2—C3—C3A	−175.36 (16)	C4—C3A—C7A—N7	2.8 (3)
C2—C3—C3A—C4	177.3 (2)	C3—C3A—C7A—N7	−178.39 (16)
C2—C3—C3A—C7A	−1.13 (19)	C3—C2—C8—C13	−178.33 (18)
C3—C3A—C4—C5	180.0 (2)	N1—C2—C8—C13	5.2 (3)
C7A—C3A—C4—C5	−1.8 (3)	C3—C2—C8—C9	4.5 (3)
C3—C3A—C4—Cl1	1.1 (3)	N1—C2—C8—C9	−171.98 (17)
C7A—C3A—C4—Cl1	179.34 (13)	C13—C8—C9—C10	−0.7 (3)
C3A—C4—C5—C6	−0.3 (3)	C2—C8—C9—C10	176.57 (18)
Cl1—C4—C5—C6	178.58 (14)	C8—C9—C10—C11	0.3 (3)
C4—C5—C6—N7	1.5 (3)	C9—C10—C11—C12	1.0 (3)
C5—C6—N7—C7A	−0.4 (3)	C10—C11—C12—C13	−1.8 (3)
C5—C6—N7—C14	−179.51 (17)	C9—C8—C13—C12	−0.2 (3)
C2—N1—C7A—N7	179.07 (17)	C2—C8—C13—C12	−177.44 (17)
C2—N1—C7A—C3A	0.0 (2)	C11—C12—C13—C8	1.4 (3)
C6—N7—C7A—N1	179.26 (18)	C6—N7—C14—O15	−68.9 (2)
C14—N7—C7A—N1	−1.7 (3)	C7A—N7—C14—O15	111.99 (17)
C6—N7—C7A—C3A	−1.8 (3)	N7—C14—O15—C16	−73.6 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C5—H5···O15ⁱ	0.95	2.32	3.237 (2)	162

Symmetry code: (i) −x+1, y−1/2, −z+3/2.

Experimental details

Crystal data
Chemical formula	C₁₅H₁₃ClN₂O
M_r	272.72
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	173
a, b, c (Å)	8.4785 (8), 9.6576 (10), 15.8560 (16)
V (Å³)	1298.3 (2)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.29
Crystal size (mm)	0.32 × 0.21 × 0.08

Data collection
Diffractometer	Bruker SMART APEXII diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	5977, 3084, 2667
R_int	0.028
(sin θ/λ)_max (Å⁻¹)	0.659

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.037, 0.079, 1.03
No. of reflections	3084
No. of parameters	173
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.21, −0.22
Absolute structure	Flack (1983), 1294 Friedel pairs
Absolute structure parameter	0.02 (6)

Computer programs: APEX2 (Bruker, 2006), SAINT (Bruker, 2006), 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
C5—H5···O15ⁱ	0.95	2.32	3.237 (2)	162

Symmetry code: (i) −x+1, y−1/2, −z+3/2.

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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