organic compounds
N-[(3RS,4RS)-1-Benzyl-4-methylpiperidin-3-yl]-5-nitro-1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridine-4-amine
aEberhard-Karls-University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany, and bInstitute of Organic Chemistry, University Mainz, Duesbergweg 10-14, 55099 Mainz, Germany
*Correspondence e-mail: stefan.laufer@uni-tuebingen.de
The pyrrolopyridine system in the title compound, C27H29N5O4S, is oriented at a dihedral angle of 71.20 (5)° towards the phenyl ring of the tosyl residue and at a dihedral angle of 45.43 (4)° towards the benzyl group. The structure shows an intramolecular N—H⋯O and a weak intramolecular N—H⋯N hydrogen bond. The piperidine ring adopts a chair conformation, with the cis substituents displaying a torsion angle of −54.59 (18)°.
Experimental
Crystal data
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Data collection
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Refinement
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Data collection: APEX2 (Bruker, 2006); cell APEX2; data reduction: APEX2; 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
https://doi.org/10.1107/S1600536812039979/bt6841sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536812039979/bt6841Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S1600536812039979/bt6841Isup3.cml
The compound was prepared by nucleophilic substitution of 4-chloro-5-nitro-1-tosyl-1H-pyrrolo[2,3-b]pyridine with cis-1-benzyl-3-aminopiperidine in the presence of tertiary amine base. A mixture of 4-chloro-5-nitro-1-tosyl-1H-pyrrolo[2,3-b]pyridine (0.624 g, 1.778 mmol), cis-1-benzyl-3-aminopiperidine-dihydrobromide (0.781 g, 2.133 mmol) and diisopropylethylamine (1.9 ml, 10.666 mmol) in 2-propanol (3 ml) was heated in a microwave reactor at 353 K for 1 h. The reaction media was concentrated under vacuum and the product precipitated from methanol to yield 0.855 g (92%) of the title compound. Crystals were obtained by recrystallization in methanol at 277 K.
All hydrogen atom were located in a difference Fourier map. Nevertheless, they were refined using a riding model with N—H = 0.92 Å, C—H = 0.95 Å (aromatic) or 0.98–0.99 Å (sp3 C-atom). The isotropic displacement parameters were set to 1.2–1.5 times of the Ueq of the parent atom.
N-(1-benzyl-4-methylpiperidin-3-yl)-5-nitro-1-tosyl-1H- pyrrolo[2,3-b]pyridine-4-amine is an important intermediate in the synthesis of tricyclic
being inhibitors of Janus kinases (Hoffmann-La Roche AG, 2011).The tosyl residue is oriented in a dihedral angle of 71.2 (0)° towards the pyrrolo-pyridine system and shows a dihedral angle of 45.4 (0)° to the benzyl group (Fig. 1). The methylene group in the title compound presents an angle of 112.0 (5)° between the phenyl and piperidine residue. The equatorial methyl and the axial pyrrolo-pyridine substituent of the piperidine show a torsion angle of 54.5 (9)°. The intramolecular hydrogen bonds N23—H23···O21 1.95 Å and N23—H23···N26 2.35 Å stabilize the
(Tabl. 1).For inhibitors of Janus kinases, see: Hoffmann-La Roche AG (2011).
Data collection: APEX2 (Bruker, 2006); cell
APEX2 (Bruker, 2006); data reduction: APEX2 (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).Fig. 1. Crystal structure of the title compound with labelling and displacement ellipsoids drawn at the 50% probability level. Hydrogen bonds are represented as dashed lines. |
C27H29N5O4S | F(000) = 1096 |
Mr = 519.61 | Dx = 1.334 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ybc | Cell parameters from 5909 reflections |
a = 17.2626 (10) Å | θ = 2.4–27.4° |
b = 11.5411 (8) Å | µ = 0.17 mm−1 |
c = 13.1313 (9) Å | T = 173 K |
β = 98.443 (3)° | Plate, yellow |
V = 2587.8 (3) Å3 | 0.50 × 0.20 × 0.08 mm |
Z = 4 |
Bruker APEXII diffractometer | 4286 reflections with I > 2σ(I) |
Radiation source: sealed Tube | Rint = 0.035 |
Graphite monochromator | θmax = 27.9°, θmin = 2.1° |
CCD scan | h = −22→22 |
25499 measured reflections | k = −12→15 |
6140 independent reflections | l = −17→17 |
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)] = 0.039 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.117 | H-atom parameters constrained |
S = 1.02 | w = 1/[σ2(Fo2) + (0.0633P)2 + 0.2813P] where P = (Fo2 + 2Fc2)/3 |
6140 reflections | (Δ/σ)max < 0.001 |
336 parameters | Δρmax = 0.25 e Å−3 |
0 restraints | Δρmin = −0.35 e Å−3 |
C27H29N5O4S | V = 2587.8 (3) Å3 |
Mr = 519.61 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 17.2626 (10) Å | µ = 0.17 mm−1 |
b = 11.5411 (8) Å | T = 173 K |
c = 13.1313 (9) Å | 0.50 × 0.20 × 0.08 mm |
β = 98.443 (3)° |
Bruker APEXII diffractometer | 4286 reflections with I > 2σ(I) |
25499 measured reflections | Rint = 0.035 |
6140 independent reflections |
R[F2 > 2σ(F2)] = 0.039 | 0 restraints |
wR(F2) = 0.117 | H-atom parameters constrained |
S = 1.02 | Δρmax = 0.25 e Å−3 |
6140 reflections | Δρmin = −0.35 e Å−3 |
336 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
N1 | 0.25756 (7) | 0.38269 (12) | 0.13550 (10) | 0.0321 (3) | |
C2 | 0.30403 (10) | 0.38599 (15) | 0.05701 (12) | 0.0341 (4) | |
H2 | 0.2851 | 0.3892 | −0.0146 | 0.041* | |
C3 | 0.37997 (10) | 0.38382 (15) | 0.09919 (12) | 0.0328 (4) | |
H3 | 0.4234 | 0.3859 | 0.0624 | 0.039* | |
C4 | 0.38439 (9) | 0.37788 (13) | 0.20968 (11) | 0.0261 (3) | |
C5 | 0.44591 (8) | 0.37411 (12) | 0.29571 (11) | 0.0249 (3) | |
C6 | 0.41701 (9) | 0.37441 (13) | 0.39271 (11) | 0.0257 (3) | |
C7 | 0.33663 (9) | 0.37230 (14) | 0.39967 (12) | 0.0303 (3) | |
H7 | 0.3220 | 0.3714 | 0.4666 | 0.036* | |
N8 | 0.27971 (8) | 0.37148 (12) | 0.32056 (10) | 0.0339 (3) | |
C9 | 0.30663 (9) | 0.37682 (13) | 0.22942 (12) | 0.0279 (3) | |
S10 | 0.15864 (2) | 0.37973 (4) | 0.11393 (3) | 0.03343 (12) | |
O11 | 0.13997 (7) | 0.40111 (11) | 0.00604 (9) | 0.0432 (3) | |
O12 | 0.13179 (7) | 0.45534 (11) | 0.18685 (10) | 0.0425 (3) | |
C13 | 0.13327 (9) | 0.23692 (14) | 0.13895 (12) | 0.0302 (3) | |
C14 | 0.12459 (9) | 0.15711 (16) | 0.05869 (13) | 0.0347 (4) | |
H14 | 0.1380 | 0.1774 | −0.0066 | 0.042* | |
C15 | 0.09609 (10) | 0.04762 (15) | 0.07540 (13) | 0.0362 (4) | |
H15 | 0.0898 | −0.0073 | 0.0209 | 0.043* | |
C16 | 0.07654 (9) | 0.01692 (15) | 0.17065 (13) | 0.0341 (4) | |
C17 | 0.08870 (10) | 0.09693 (16) | 0.25082 (13) | 0.0369 (4) | |
H17 | 0.0773 | 0.0757 | 0.3169 | 0.044* | |
C18 | 0.11701 (9) | 0.20656 (16) | 0.23604 (13) | 0.0350 (4) | |
H18 | 0.1253 | 0.2604 | 0.2913 | 0.042* | |
C19 | 0.04180 (12) | −0.10047 (17) | 0.18642 (16) | 0.0490 (5) | |
H19A | 0.0185 | −0.1323 | 0.1197 | 0.073* | |
H19B | 0.0013 | −0.0927 | 0.2310 | 0.073* | |
H19C | 0.0830 | −0.1526 | 0.2188 | 0.073* | |
N20 | 0.46852 (8) | 0.37004 (11) | 0.48969 (10) | 0.0286 (3) | |
O21 | 0.54003 (7) | 0.35745 (12) | 0.49078 (9) | 0.0436 (3) | |
O22 | 0.44069 (7) | 0.37755 (12) | 0.57041 (9) | 0.0450 (3) | |
N23 | 0.52257 (7) | 0.37061 (11) | 0.28858 (10) | 0.0283 (3) | |
H23 | 0.5578 | 0.3611 | 0.3478 | 0.034* | |
C24 | 0.56077 (9) | 0.35130 (14) | 0.19766 (12) | 0.0283 (3) | |
H24 | 0.5213 | 0.3224 | 0.1399 | 0.034* | |
C25 | 0.62288 (9) | 0.25754 (14) | 0.22722 (13) | 0.0318 (4) | |
H25A | 0.5979 | 0.1867 | 0.2498 | 0.038* | |
H25B | 0.6486 | 0.2377 | 0.1669 | 0.038* | |
N26 | 0.68097 (7) | 0.30109 (11) | 0.31072 (10) | 0.0298 (3) | |
C27 | 0.72550 (9) | 0.39528 (15) | 0.27122 (13) | 0.0344 (4) | |
H27A | 0.7483 | 0.3682 | 0.2105 | 0.041* | |
H27B | 0.7688 | 0.4198 | 0.3248 | 0.041* | |
C28 | 0.67087 (9) | 0.49632 (15) | 0.24132 (13) | 0.0344 (4) | |
H28A | 0.7001 | 0.5584 | 0.2115 | 0.041* | |
H28B | 0.6528 | 0.5276 | 0.3040 | 0.041* | |
C29 | 0.59923 (9) | 0.46310 (14) | 0.16334 (12) | 0.0304 (3) | |
H29 | 0.6182 | 0.4459 | 0.0966 | 0.036* | |
C30 | 0.54279 (11) | 0.56531 (15) | 0.14510 (14) | 0.0387 (4) | |
H30A | 0.5207 | 0.5815 | 0.2082 | 0.058* | |
H30B | 0.5004 | 0.5463 | 0.0894 | 0.058* | |
H30C | 0.5710 | 0.6337 | 0.1259 | 0.058* | |
C31 | 0.73136 (10) | 0.20900 (15) | 0.36030 (14) | 0.0388 (4) | |
H31A | 0.7643 | 0.1782 | 0.3108 | 0.047* | |
H31B | 0.6983 | 0.1449 | 0.3795 | 0.047* | |
C32 | 0.78383 (9) | 0.25168 (15) | 0.45576 (13) | 0.0334 (4) | |
C33 | 0.75798 (10) | 0.33474 (16) | 0.51998 (13) | 0.0364 (4) | |
H33 | 0.7063 | 0.3645 | 0.5044 | 0.044* | |
C34 | 0.80684 (11) | 0.37471 (16) | 0.60677 (13) | 0.0378 (4) | |
H34 | 0.7887 | 0.4323 | 0.6492 | 0.045* | |
C35 | 0.88179 (10) | 0.33065 (16) | 0.63118 (14) | 0.0409 (4) | |
H35 | 0.9150 | 0.3570 | 0.6908 | 0.049* | |
C36 | 0.90805 (10) | 0.24790 (17) | 0.56794 (15) | 0.0446 (5) | |
H36 | 0.9595 | 0.2174 | 0.5843 | 0.054* | |
C37 | 0.85963 (10) | 0.20925 (16) | 0.48089 (15) | 0.0401 (4) | |
H37 | 0.8785 | 0.1530 | 0.4378 | 0.048* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.0277 (7) | 0.0408 (8) | 0.0267 (7) | −0.0019 (6) | −0.0003 (6) | 0.0009 (6) |
C2 | 0.0370 (9) | 0.0408 (10) | 0.0240 (8) | −0.0038 (7) | 0.0026 (7) | 0.0002 (7) |
C3 | 0.0321 (8) | 0.0401 (10) | 0.0266 (8) | −0.0028 (7) | 0.0053 (7) | −0.0004 (7) |
C4 | 0.0281 (8) | 0.0253 (8) | 0.0246 (8) | −0.0015 (6) | 0.0029 (6) | −0.0010 (6) |
C5 | 0.0271 (8) | 0.0212 (7) | 0.0261 (8) | −0.0015 (6) | 0.0031 (6) | −0.0003 (6) |
C6 | 0.0292 (8) | 0.0237 (8) | 0.0236 (8) | 0.0009 (6) | 0.0023 (6) | 0.0002 (6) |
C7 | 0.0322 (8) | 0.0351 (9) | 0.0244 (8) | 0.0023 (6) | 0.0068 (6) | 0.0003 (6) |
N8 | 0.0293 (7) | 0.0435 (9) | 0.0291 (7) | 0.0015 (6) | 0.0044 (6) | 0.0005 (6) |
C9 | 0.0277 (8) | 0.0290 (8) | 0.0257 (8) | −0.0007 (6) | −0.0002 (6) | 0.0005 (6) |
S10 | 0.0277 (2) | 0.0367 (2) | 0.0334 (2) | 0.00088 (16) | −0.00356 (16) | 0.00128 (17) |
O11 | 0.0400 (7) | 0.0491 (8) | 0.0362 (7) | −0.0019 (5) | −0.0088 (5) | 0.0102 (6) |
O12 | 0.0333 (6) | 0.0407 (7) | 0.0520 (8) | 0.0052 (5) | 0.0013 (6) | −0.0075 (6) |
C13 | 0.0230 (7) | 0.0383 (9) | 0.0280 (8) | 0.0023 (6) | −0.0000 (6) | −0.0009 (7) |
C14 | 0.0335 (9) | 0.0442 (10) | 0.0269 (8) | −0.0011 (7) | 0.0059 (7) | −0.0008 (7) |
C15 | 0.0361 (9) | 0.0387 (10) | 0.0341 (9) | 0.0031 (7) | 0.0061 (7) | −0.0058 (7) |
C16 | 0.0255 (8) | 0.0384 (10) | 0.0382 (10) | 0.0057 (7) | 0.0037 (7) | 0.0053 (7) |
C17 | 0.0329 (9) | 0.0509 (11) | 0.0271 (9) | 0.0018 (7) | 0.0044 (7) | 0.0052 (7) |
C18 | 0.0310 (8) | 0.0471 (10) | 0.0257 (8) | 0.0011 (7) | 0.0002 (7) | −0.0051 (7) |
C19 | 0.0497 (11) | 0.0448 (12) | 0.0529 (12) | −0.0017 (9) | 0.0094 (9) | 0.0082 (9) |
N20 | 0.0339 (7) | 0.0263 (7) | 0.0251 (7) | −0.0004 (5) | 0.0027 (6) | 0.0007 (5) |
O21 | 0.0289 (6) | 0.0701 (9) | 0.0303 (6) | 0.0010 (6) | −0.0004 (5) | 0.0047 (6) |
O22 | 0.0461 (7) | 0.0661 (9) | 0.0230 (6) | 0.0075 (6) | 0.0057 (5) | −0.0026 (6) |
N23 | 0.0244 (6) | 0.0367 (8) | 0.0235 (7) | −0.0032 (5) | 0.0028 (5) | −0.0005 (5) |
C24 | 0.0263 (8) | 0.0338 (9) | 0.0254 (8) | −0.0031 (6) | 0.0054 (6) | −0.0048 (6) |
C25 | 0.0286 (8) | 0.0313 (9) | 0.0355 (9) | −0.0028 (6) | 0.0048 (7) | −0.0061 (7) |
N26 | 0.0254 (6) | 0.0303 (7) | 0.0331 (7) | −0.0020 (5) | 0.0024 (6) | −0.0021 (6) |
C27 | 0.0266 (8) | 0.0424 (10) | 0.0349 (9) | −0.0085 (7) | 0.0066 (7) | −0.0012 (7) |
C28 | 0.0357 (9) | 0.0336 (9) | 0.0350 (9) | −0.0102 (7) | 0.0086 (7) | −0.0011 (7) |
C29 | 0.0332 (8) | 0.0337 (9) | 0.0252 (8) | −0.0025 (7) | 0.0072 (7) | −0.0010 (6) |
C30 | 0.0468 (10) | 0.0344 (10) | 0.0359 (10) | 0.0006 (8) | 0.0095 (8) | 0.0027 (7) |
C31 | 0.0342 (9) | 0.0367 (10) | 0.0440 (10) | 0.0054 (7) | 0.0014 (8) | −0.0058 (8) |
C32 | 0.0311 (8) | 0.0334 (9) | 0.0358 (9) | 0.0017 (7) | 0.0051 (7) | 0.0041 (7) |
C33 | 0.0315 (8) | 0.0428 (10) | 0.0347 (9) | 0.0042 (7) | 0.0043 (7) | 0.0028 (8) |
C34 | 0.0443 (10) | 0.0403 (10) | 0.0295 (9) | −0.0015 (8) | 0.0078 (7) | 0.0027 (7) |
C35 | 0.0402 (10) | 0.0455 (11) | 0.0341 (9) | −0.0083 (8) | −0.0037 (8) | 0.0096 (8) |
C36 | 0.0310 (9) | 0.0505 (12) | 0.0500 (11) | 0.0037 (8) | −0.0014 (8) | 0.0118 (9) |
C37 | 0.0358 (9) | 0.0386 (10) | 0.0457 (11) | 0.0069 (7) | 0.0049 (8) | 0.0036 (8) |
N1—C9 | 1.3916 (19) | N23—C24 | 1.4633 (19) |
N1—C2 | 1.396 (2) | N23—H23 | 0.9205 |
N1—S10 | 1.6899 (13) | C24—C25 | 1.533 (2) |
C2—C3 | 1.346 (2) | C24—C29 | 1.548 (2) |
C2—H2 | 0.9500 | C24—H24 | 1.0000 |
C3—C4 | 1.443 (2) | C25—N26 | 1.462 (2) |
C3—H3 | 0.9500 | C25—H25A | 0.9900 |
C4—C9 | 1.404 (2) | C25—H25B | 0.9900 |
C4—C5 | 1.433 (2) | N26—C31 | 1.464 (2) |
C5—N23 | 1.3409 (19) | N26—C27 | 1.469 (2) |
C5—C6 | 1.435 (2) | C27—C28 | 1.515 (2) |
C6—C7 | 1.404 (2) | C27—H27A | 0.9900 |
C6—N20 | 1.4431 (19) | C27—H27B | 0.9900 |
C7—N8 | 1.321 (2) | C28—C29 | 1.534 (2) |
C7—H7 | 0.9500 | C28—H28A | 0.9900 |
N8—C9 | 1.347 (2) | C28—H28B | 0.9900 |
S10—O12 | 1.4224 (13) | C29—C30 | 1.526 (2) |
S10—O11 | 1.4276 (12) | C29—H29 | 1.0000 |
S10—C13 | 1.7488 (17) | C30—H30A | 0.9800 |
C13—C18 | 1.390 (2) | C30—H30B | 0.9800 |
C13—C14 | 1.391 (2) | C30—H30C | 0.9800 |
C14—C15 | 1.385 (2) | C31—C32 | 1.517 (2) |
C14—H14 | 0.9500 | C31—H31A | 0.9900 |
C15—C16 | 1.388 (2) | C31—H31B | 0.9900 |
C15—H15 | 0.9500 | C32—C37 | 1.391 (2) |
C16—C17 | 1.393 (2) | C32—C33 | 1.393 (2) |
C16—C19 | 1.508 (3) | C33—C34 | 1.393 (2) |
C17—C18 | 1.380 (2) | C33—H33 | 0.9500 |
C17—H17 | 0.9500 | C34—C35 | 1.383 (3) |
C18—H18 | 0.9500 | C34—H34 | 0.9500 |
C19—H19A | 0.9800 | C35—C36 | 1.385 (3) |
C19—H19B | 0.9800 | C35—H35 | 0.9500 |
C19—H19C | 0.9800 | C36—C37 | 1.387 (3) |
N20—O22 | 1.2294 (17) | C36—H36 | 0.9500 |
N20—O21 | 1.2409 (17) | C37—H37 | 0.9500 |
C9—N1—C2 | 108.33 (13) | N23—C24—C29 | 111.99 (13) |
C9—N1—S10 | 128.04 (11) | C25—C24—C29 | 110.39 (13) |
C2—N1—S10 | 123.56 (11) | N23—C24—H24 | 109.3 |
C3—C2—N1 | 109.03 (14) | C25—C24—H24 | 109.3 |
C3—C2—H2 | 125.5 | C29—C24—H24 | 109.3 |
N1—C2—H2 | 125.5 | N26—C25—C24 | 108.94 (13) |
C2—C3—C4 | 108.60 (14) | N26—C25—H25A | 109.9 |
C2—C3—H3 | 125.7 | C24—C25—H25A | 109.9 |
C4—C3—H3 | 125.7 | N26—C25—H25B | 109.9 |
C9—C4—C5 | 118.18 (13) | C24—C25—H25B | 109.9 |
C9—C4—C3 | 105.97 (13) | H25A—C25—H25B | 108.3 |
C5—C4—C3 | 135.85 (14) | C25—N26—C31 | 112.41 (13) |
N23—C5—C4 | 124.80 (14) | C25—N26—C27 | 109.05 (13) |
N23—C5—C6 | 122.51 (13) | C31—N26—C27 | 112.75 (13) |
C4—C5—C6 | 112.69 (13) | N26—C27—C28 | 108.85 (13) |
C7—C6—C5 | 122.25 (14) | N26—C27—H27A | 109.9 |
C7—C6—N20 | 115.39 (13) | C28—C27—H27A | 109.9 |
C5—C6—N20 | 122.27 (13) | N26—C27—H27B | 109.9 |
N8—C7—C6 | 125.24 (15) | C28—C27—H27B | 109.9 |
N8—C7—H7 | 117.4 | H27A—C27—H27B | 108.3 |
C6—C7—H7 | 117.4 | C27—C28—C29 | 113.01 (14) |
C7—N8—C9 | 112.61 (13) | C27—C28—H28A | 109.0 |
N8—C9—N1 | 123.02 (14) | C29—C28—H28A | 109.0 |
N8—C9—C4 | 128.92 (14) | C27—C28—H28B | 109.0 |
N1—C9—C4 | 108.06 (13) | C29—C28—H28B | 109.0 |
O12—S10—O11 | 120.90 (8) | H28A—C28—H28B | 107.8 |
O12—S10—N1 | 107.21 (7) | C30—C29—C28 | 110.19 (14) |
O11—S10—N1 | 103.78 (7) | C30—C29—C24 | 113.50 (13) |
O12—S10—C13 | 109.66 (8) | C28—C29—C24 | 110.62 (13) |
O11—S10—C13 | 108.85 (8) | C30—C29—H29 | 107.4 |
N1—S10—C13 | 105.21 (7) | C28—C29—H29 | 107.4 |
C18—C13—C14 | 120.95 (16) | C24—C29—H29 | 107.4 |
C18—C13—S10 | 119.98 (13) | C29—C30—H30A | 109.5 |
C14—C13—S10 | 118.93 (13) | C29—C30—H30B | 109.5 |
C15—C14—C13 | 119.02 (16) | H30A—C30—H30B | 109.5 |
C15—C14—H14 | 120.5 | C29—C30—H30C | 109.5 |
C13—C14—H14 | 120.5 | H30A—C30—H30C | 109.5 |
C14—C15—C16 | 120.97 (16) | H30B—C30—H30C | 109.5 |
C14—C15—H15 | 119.5 | N26—C31—C32 | 112.05 (14) |
C16—C15—H15 | 119.5 | N26—C31—H31A | 109.2 |
C15—C16—C17 | 118.82 (16) | C32—C31—H31A | 109.2 |
C15—C16—C19 | 120.47 (16) | N26—C31—H31B | 109.2 |
C17—C16—C19 | 120.71 (16) | C32—C31—H31B | 109.2 |
C18—C17—C16 | 121.24 (16) | H31A—C31—H31B | 107.9 |
C18—C17—H17 | 119.4 | C37—C32—C33 | 118.20 (16) |
C16—C17—H17 | 119.4 | C37—C32—C31 | 120.57 (16) |
C17—C18—C13 | 118.91 (16) | C33—C32—C31 | 121.22 (14) |
C17—C18—H18 | 120.5 | C32—C33—C34 | 120.92 (16) |
C13—C18—H18 | 120.5 | C32—C33—H33 | 119.5 |
C16—C19—H19A | 109.5 | C34—C33—H33 | 119.5 |
C16—C19—H19B | 109.5 | C35—C34—C33 | 120.08 (17) |
H19A—C19—H19B | 109.5 | C35—C34—H34 | 120.0 |
C16—C19—H19C | 109.5 | C33—C34—H34 | 120.0 |
H19A—C19—H19C | 109.5 | C34—C35—C36 | 119.47 (17) |
H19B—C19—H19C | 109.5 | C34—C35—H35 | 120.3 |
O22—N20—O21 | 120.82 (13) | C36—C35—H35 | 120.3 |
O22—N20—C6 | 119.35 (13) | C35—C36—C37 | 120.35 (16) |
O21—N20—C6 | 119.82 (13) | C35—C36—H36 | 119.8 |
C5—N23—C24 | 128.99 (13) | C37—C36—H36 | 119.8 |
C5—N23—H23 | 118.8 | C36—C37—C32 | 120.97 (18) |
C24—N23—H23 | 110.5 | C36—C37—H37 | 119.5 |
N23—C24—C25 | 106.45 (13) | C32—C37—H37 | 119.5 |
C9—N1—C2—C3 | −0.75 (19) | C14—C15—C16—C17 | −2.3 (2) |
S10—N1—C2—C3 | −177.98 (12) | C14—C15—C16—C19 | 176.94 (16) |
N1—C2—C3—C4 | 0.49 (19) | C15—C16—C17—C18 | 2.3 (2) |
C2—C3—C4—C9 | −0.05 (18) | C19—C16—C17—C18 | −176.92 (16) |
C2—C3—C4—C5 | −179.48 (17) | C16—C17—C18—C13 | 0.2 (2) |
C9—C4—C5—N23 | 177.61 (14) | C14—C13—C18—C17 | −2.8 (2) |
C3—C4—C5—N23 | −3.0 (3) | S10—C13—C18—C17 | 172.83 (12) |
C9—C4—C5—C6 | −2.37 (19) | C7—C6—N20—O22 | −7.8 (2) |
C3—C4—C5—C6 | 177.00 (17) | C5—C6—N20—O22 | 175.66 (14) |
N23—C5—C6—C7 | −176.77 (14) | C7—C6—N20—O21 | 171.34 (14) |
C4—C5—C6—C7 | 3.2 (2) | C5—C6—N20—O21 | −5.2 (2) |
N23—C5—C6—N20 | −0.5 (2) | C4—C5—N23—C24 | −10.8 (2) |
C4—C5—C6—N20 | 179.48 (13) | C6—C5—N23—C24 | 169.18 (14) |
C5—C6—C7—N8 | −1.0 (2) | C5—N23—C24—C25 | −130.72 (15) |
N20—C6—C7—N8 | −177.51 (14) | C5—N23—C24—C29 | 108.55 (17) |
C6—C7—N8—C9 | −2.1 (2) | N23—C24—C25—N26 | −62.82 (15) |
C7—N8—C9—N1 | −176.84 (14) | C29—C24—C25—N26 | 58.93 (17) |
C7—N8—C9—C4 | 3.0 (2) | C24—C25—N26—C31 | 166.21 (13) |
C2—N1—C9—N8 | −179.41 (15) | C24—C25—N26—C27 | −67.99 (16) |
S10—N1—C9—N8 | −2.3 (2) | C25—N26—C27—C28 | 65.74 (16) |
C2—N1—C9—C4 | 0.71 (17) | C31—N26—C27—C28 | −168.66 (13) |
S10—N1—C9—C4 | 177.77 (11) | N26—C27—C28—C29 | −55.95 (18) |
C5—C4—C9—N8 | −0.7 (2) | C27—C28—C29—C30 | 174.23 (14) |
C3—C4—C9—N8 | 179.72 (16) | C27—C28—C29—C24 | 47.91 (18) |
C5—C4—C9—N1 | 179.14 (13) | N23—C24—C29—C30 | −54.59 (18) |
C3—C4—C9—N1 | −0.40 (17) | C25—C24—C29—C30 | −173.00 (13) |
C9—N1—S10—O12 | 44.89 (16) | N23—C24—C29—C28 | 69.86 (16) |
C2—N1—S10—O12 | −138.45 (14) | C25—C24—C29—C28 | −48.55 (17) |
C9—N1—S10—O11 | 173.91 (13) | C25—N26—C31—C32 | −172.15 (14) |
C2—N1—S10—O11 | −9.43 (16) | C27—N26—C31—C32 | 64.09 (18) |
C9—N1—S10—C13 | −71.80 (15) | N26—C31—C32—C37 | −144.17 (16) |
C2—N1—S10—C13 | 104.86 (14) | N26—C31—C32—C33 | 35.3 (2) |
O12—S10—C13—C18 | −21.20 (15) | C37—C32—C33—C34 | 0.3 (3) |
O11—S10—C13—C18 | −155.49 (12) | C31—C32—C33—C34 | −179.11 (16) |
N1—S10—C13—C18 | 93.81 (13) | C32—C33—C34—C35 | −1.0 (3) |
O12—S10—C13—C14 | 154.50 (12) | C33—C34—C35—C36 | 0.9 (3) |
O11—S10—C13—C14 | 20.22 (15) | C34—C35—C36—C37 | −0.1 (3) |
N1—S10—C13—C14 | −90.49 (13) | C35—C36—C37—C32 | −0.6 (3) |
C18—C13—C14—C15 | 2.8 (2) | C33—C32—C37—C36 | 0.5 (3) |
S10—C13—C14—C15 | −172.86 (12) | C31—C32—C37—C36 | 179.90 (16) |
C13—C14—C15—C16 | −0.2 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
N23—H23···O21 | 0.92 | 1.95 | 2.6322 (17) | 130 |
N23—H23···N26 | 0.92 | 2.35 | 2.8235 (18) | 111 |
Experimental details
Crystal data | |
Chemical formula | C27H29N5O4S |
Mr | 519.61 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 173 |
a, b, c (Å) | 17.2626 (10), 11.5411 (8), 13.1313 (9) |
β (°) | 98.443 (3) |
V (Å3) | 2587.8 (3) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.17 |
Crystal size (mm) | 0.50 × 0.20 × 0.08 |
Data collection | |
Diffractometer | Bruker APEXII |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 25499, 6140, 4286 |
Rint | 0.035 |
(sin θ/λ)max (Å−1) | 0.659 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.039, 0.117, 1.02 |
No. of reflections | 6140 |
No. of parameters | 336 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.25, −0.35 |
Computer programs: APEX2 (Bruker, 2006), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2009).
D—H···A | D—H | H···A | D···A | D—H···A |
N23—H23···O21 | 0.92 | 1.95 | 2.6322 (17) | 130 |
N23—H23···N26 | 0.92 | 2.35 | 2.8235 (18) | 111 |
Acknowledgements
The authors thank Maria Leticia Barbosa, Matthias Gehringer and Peter Keck for suggestions and comments.
References
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. Web of Science CrossRef CAS IUCr Journals Google Scholar
Bruker (2006). APEX2. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Hoffmann-La Roche AG (2011). World Patent WO 2011/086053 A1. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Spek, A. L. (2009). Acta Cryst. D65, 148–155. Web of Science CrossRef CAS IUCr Journals Google Scholar
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N-(1-benzyl-4-methylpiperidin-3-yl)-5-nitro-1-tosyl-1H- pyrrolo[2,3-b]pyridine-4-amine is an important intermediate in the synthesis of tricyclic heterocyclic compounds being inhibitors of Janus kinases (Hoffmann-La Roche AG, 2011).
The tosyl residue is oriented in a dihedral angle of 71.2 (0)° towards the pyrrolo-pyridine system and shows a dihedral angle of 45.4 (0)° to the benzyl group (Fig. 1). The methylene group in the title compound presents an angle of 112.0 (5)° between the phenyl and piperidine residue. The equatorial methyl and the axial pyrrolo-pyridine substituent of the piperidine show a torsion angle of 54.5 (9)°. The intramolecular hydrogen bonds N23—H23···O21 1.95 Å and N23—H23···N26 2.35 Å stabilize the molecular conformation (Tabl. 1).