Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807050441/xu2339sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807050441/xu2339Isup2.hkl |
CCDC reference: 667386
N-Carbobenzyloxy-L-proline (1.0 g, 4 mmol) and triethylamine (0.4 g, 4 mmol) were dissolved in THF (15 ml). To the solution was added dropwise ethylchloroformate (0.44 g, 4 mmol) at 273 K. After the solution was stirred for 30 min, 5-chloropyridin-2-amine (4 mmol) was added over a period of 10 min. The resulting solution was stirred at 273 K for 1 h and then stirred at room temperature for a further 12 h, and finaly refluxed for 3 h. After cooling down to room temperature, the solution was diluted with ethyl acetate. After filtration and removal of solvent under reduced pressure, the residue was purified through column chromatography on silica gel to give the title compound. Colourless single crystals were obtained by recrystallization from an ethanol solution.
H atoms were placed at calculated positions with C–H = 0.93 or 0.97 Å and N—H = 0.86 Å, and refined using a riding model with Uiso(H) = 1.2Ueq(C,N).
The title compound is an important inhibitor of peptidyl deformylase (Patel et al., 2002). Its crystal structure is presented here.
The molecular structure is shown in Fig. 1. Bond lengths and angles are normal. The dihedral angle between the C6-benzene and O1/O2/N1/C8 planes is 50.56 (7)° and that between N3-pyridine and O3/N2/C12/C13 planes is 11.34 (11)°. The crystal packing is stabilized by N—H···O and C—H···O hydrogen bonding (Table 1).
For general background, see: Patel et al. (1994 or??2002). For related structures, see He (2006); Kang et al. (2007).
Data collection: APEX2 (Bruker, 2006); cell refinement: SAINT (Bruker, 2006); data reduction: SAINT (Bruker, 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 2002); software used to prepare material for publication: SHELXTL (Bruker, 2002).
Fig. 1. The molecular structure of (I) with 30% probability displacement ellipsoids (arbitrary spheres for H atoms). |
C18H18ClN3O3 | F(000) = 752 |
Mr = 359.80 | Dx = 1.380 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 8860 reflections |
a = 6.2419 (14) Å | θ = 1.7–27.5° |
b = 15.785 (4) Å | µ = 0.24 mm−1 |
c = 17.574 (4) Å | T = 293 K |
V = 1731.5 (7) Å3 | Block, colourless |
Z = 4 | 0.39 × 0.32 × 0.21 mm |
Bruker APEXII area-detector diffractometer | 3602 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.021 |
Graphite monochromator | θmax = 27.5°, θmin = 1.7° |
ω scans | h = −8→8 |
22340 measured reflections | k = −20→20 |
3991 independent reflections | l = −22→22 |
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)] = 0.032 | H-atom parameters constrained |
wR(F2) = 0.088 | w = 1/[σ2(Fo2) + (0.0474P)2 + 0.1826P] where P = (Fo2 + 2Fc2)/3 |
S = 1.04 | (Δ/σ)max = 0.001 |
3991 reflections | Δρmax = 0.31 e Å−3 |
226 parameters | Δρmin = −0.17 e Å−3 |
0 restraints | Absolute structure: Flack (1983), Friedel pairs 1686 |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: 0.02 (6) |
C18H18ClN3O3 | V = 1731.5 (7) Å3 |
Mr = 359.80 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 6.2419 (14) Å | µ = 0.24 mm−1 |
b = 15.785 (4) Å | T = 293 K |
c = 17.574 (4) Å | 0.39 × 0.32 × 0.21 mm |
Bruker APEXII area-detector diffractometer | 3602 reflections with I > 2σ(I) |
22340 measured reflections | Rint = 0.021 |
3991 independent reflections |
R[F2 > 2σ(F2)] = 0.032 | H-atom parameters constrained |
wR(F2) = 0.088 | Δρmax = 0.31 e Å−3 |
S = 1.04 | Δρmin = −0.17 e Å−3 |
3991 reflections | Absolute structure: Flack (1983), Friedel pairs 1686 |
226 parameters | Absolute structure parameter: 0.02 (6) |
0 restraints |
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 | ||
Cl1 | 0.95345 (10) | −0.20996 (3) | 0.56412 (3) | 0.07666 (17) | |
O1 | −0.26937 (16) | 0.14607 (7) | 0.81673 (7) | 0.0519 (3) | |
O2 | 0.06298 (16) | 0.14500 (7) | 0.76457 (6) | 0.0501 (3) | |
O3 | 0.1628 (2) | −0.07143 (9) | 0.80223 (8) | 0.0693 (4) | |
N1 | 0.0084 (2) | 0.07818 (8) | 0.87283 (7) | 0.0475 (3) | |
N2 | 0.4701 (2) | −0.00045 (8) | 0.77641 (7) | 0.0454 (3) | |
H2B | 0.5368 | 0.0460 | 0.7861 | 0.054* | |
N3 | 0.7472 (2) | −0.02296 (8) | 0.69420 (8) | 0.0536 (3) | |
C1 | 0.1709 (3) | 0.21399 (11) | 0.65153 (8) | 0.0496 (3) | |
C2 | 0.3125 (3) | 0.15325 (12) | 0.62553 (10) | 0.0624 (4) | |
H2A | 0.2895 | 0.0966 | 0.6374 | 0.075* | |
C3 | 0.4874 (3) | 0.17575 (12) | 0.58222 (10) | 0.0653 (5) | |
H3A | 0.5817 | 0.1342 | 0.5653 | 0.078* | |
C4 | 0.5231 (3) | 0.25886 (13) | 0.56400 (10) | 0.0640 (5) | |
H4A | 0.6412 | 0.2741 | 0.5348 | 0.077* | |
C5 | 0.3837 (3) | 0.31895 (12) | 0.58906 (12) | 0.0688 (5) | |
H5A | 0.4071 | 0.3755 | 0.5766 | 0.083* | |
C6 | 0.2077 (3) | 0.29728 (11) | 0.63282 (10) | 0.0581 (4) | |
H6A | 0.1142 | 0.3392 | 0.6496 | 0.070* | |
C7 | −0.0186 (3) | 0.19016 (14) | 0.69944 (11) | 0.0647 (5) | |
H7A | −0.0953 | 0.2405 | 0.7156 | 0.078* | |
H7B | −0.1160 | 0.1545 | 0.6707 | 0.078* | |
C8 | −0.0816 (2) | 0.12430 (9) | 0.81787 (9) | 0.0435 (3) | |
C9 | −0.1015 (3) | 0.05911 (12) | 0.94413 (10) | 0.0595 (4) | |
H9A | −0.1788 | 0.0059 | 0.9409 | 0.071* | |
H9B | −0.2007 | 0.1039 | 0.9578 | 0.071* | |
C10 | 0.0824 (3) | 0.05351 (14) | 1.00050 (11) | 0.0692 (5) | |
H10A | 0.1218 | 0.1092 | 1.0192 | 0.083* | |
H10B | 0.0453 | 0.0177 | 1.0434 | 0.083* | |
C11 | 0.2603 (3) | 0.01519 (13) | 0.95454 (10) | 0.0615 (4) | |
H11A | 0.2470 | −0.0460 | 0.9528 | 0.074* | |
H11B | 0.3988 | 0.0297 | 0.9760 | 0.074* | |
C12 | 0.2343 (2) | 0.05386 (10) | 0.87433 (9) | 0.0452 (3) | |
H12A | 0.3268 | 0.1036 | 0.8682 | 0.054* | |
C13 | 0.2818 (2) | −0.01228 (9) | 0.81333 (9) | 0.0443 (3) | |
C14 | 0.5688 (2) | −0.05511 (9) | 0.72421 (8) | 0.0429 (3) | |
C15 | 0.4942 (3) | −0.13553 (10) | 0.70621 (10) | 0.0559 (4) | |
H15A | 0.3676 | −0.1560 | 0.7272 | 0.067* | |
C16 | 0.6120 (3) | −0.18417 (10) | 0.65659 (10) | 0.0591 (4) | |
H16A | 0.5669 | −0.2384 | 0.6434 | 0.071* | |
C17 | 0.7966 (3) | −0.15139 (10) | 0.62707 (9) | 0.0526 (4) | |
C18 | 0.8584 (3) | −0.07138 (12) | 0.64670 (10) | 0.0577 (4) | |
H18A | 0.9840 | −0.0498 | 0.6259 | 0.069* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Cl1 | 0.0931 (4) | 0.0654 (3) | 0.0714 (3) | 0.0266 (3) | 0.0201 (3) | −0.0079 (2) |
O1 | 0.0333 (5) | 0.0546 (6) | 0.0679 (7) | 0.0003 (5) | 0.0041 (5) | −0.0087 (5) |
O2 | 0.0356 (5) | 0.0637 (6) | 0.0511 (6) | 0.0016 (5) | 0.0046 (4) | 0.0090 (5) |
O3 | 0.0523 (6) | 0.0655 (7) | 0.0901 (9) | −0.0205 (6) | 0.0217 (7) | −0.0175 (7) |
N1 | 0.0359 (6) | 0.0534 (7) | 0.0533 (7) | 0.0013 (5) | 0.0124 (5) | 0.0040 (6) |
N2 | 0.0392 (6) | 0.0433 (6) | 0.0536 (7) | −0.0051 (5) | 0.0092 (5) | −0.0038 (5) |
N3 | 0.0452 (7) | 0.0544 (8) | 0.0611 (8) | −0.0054 (6) | 0.0140 (6) | −0.0098 (6) |
C1 | 0.0451 (8) | 0.0596 (9) | 0.0440 (7) | 0.0048 (7) | −0.0019 (6) | 0.0045 (7) |
C2 | 0.0672 (11) | 0.0545 (9) | 0.0655 (10) | 0.0071 (8) | 0.0099 (9) | 0.0058 (8) |
C3 | 0.0619 (11) | 0.0719 (11) | 0.0621 (10) | 0.0156 (9) | 0.0104 (9) | −0.0038 (9) |
C4 | 0.0516 (10) | 0.0830 (13) | 0.0573 (10) | −0.0071 (9) | 0.0055 (8) | 0.0029 (9) |
C5 | 0.0689 (12) | 0.0586 (10) | 0.0789 (12) | −0.0106 (9) | 0.0054 (10) | 0.0026 (9) |
C6 | 0.0559 (10) | 0.0561 (9) | 0.0622 (9) | 0.0067 (8) | 0.0023 (8) | −0.0062 (8) |
C7 | 0.0445 (8) | 0.0875 (13) | 0.0620 (10) | 0.0099 (9) | 0.0012 (8) | 0.0202 (9) |
C8 | 0.0350 (7) | 0.0429 (7) | 0.0527 (8) | −0.0051 (6) | 0.0051 (6) | −0.0083 (6) |
C9 | 0.0516 (9) | 0.0617 (10) | 0.0651 (10) | 0.0003 (8) | 0.0228 (8) | 0.0061 (8) |
C10 | 0.0761 (13) | 0.0759 (12) | 0.0555 (10) | 0.0100 (10) | 0.0166 (9) | 0.0082 (9) |
C11 | 0.0577 (10) | 0.0761 (12) | 0.0506 (9) | 0.0106 (9) | 0.0049 (8) | 0.0018 (8) |
C12 | 0.0351 (7) | 0.0506 (8) | 0.0498 (8) | 0.0005 (6) | 0.0073 (6) | 0.0003 (6) |
C13 | 0.0368 (7) | 0.0462 (8) | 0.0498 (8) | −0.0028 (6) | 0.0057 (6) | 0.0034 (6) |
C14 | 0.0403 (7) | 0.0455 (7) | 0.0429 (7) | 0.0008 (6) | 0.0037 (6) | 0.0011 (6) |
C15 | 0.0595 (10) | 0.0471 (8) | 0.0611 (9) | −0.0075 (7) | 0.0118 (8) | −0.0007 (7) |
C16 | 0.0752 (12) | 0.0412 (7) | 0.0610 (10) | 0.0023 (8) | 0.0059 (9) | −0.0033 (7) |
C17 | 0.0603 (10) | 0.0505 (8) | 0.0470 (8) | 0.0160 (7) | 0.0028 (7) | −0.0004 (7) |
C18 | 0.0500 (9) | 0.0618 (10) | 0.0611 (10) | −0.0013 (8) | 0.0144 (8) | −0.0059 (8) |
Cl1—C17 | 1.7429 (16) | C5—H5A | 0.9300 |
O1—C8 | 1.2215 (18) | C6—H6A | 0.9300 |
O2—C8 | 1.3411 (18) | C7—H7A | 0.9700 |
O2—C7 | 1.441 (2) | C7—H7B | 0.9700 |
O3—C13 | 1.2091 (18) | C9—C10 | 1.519 (3) |
N1—C8 | 1.334 (2) | C9—H9A | 0.9700 |
N1—C9 | 1.4601 (19) | C9—H9B | 0.9700 |
N1—C12 | 1.462 (2) | C10—C11 | 1.501 (3) |
N2—C13 | 1.3552 (18) | C10—H10A | 0.9700 |
N2—C14 | 1.4018 (18) | C10—H10B | 0.9700 |
N2—H2B | 0.8600 | C11—C12 | 1.545 (2) |
N3—C18 | 1.328 (2) | C11—H11A | 0.9700 |
N3—C14 | 1.3326 (19) | C11—H11B | 0.9700 |
C1—C6 | 1.374 (2) | C12—C13 | 1.526 (2) |
C1—C2 | 1.382 (2) | C12—H12A | 0.9800 |
C1—C7 | 1.500 (2) | C14—C15 | 1.389 (2) |
C2—C3 | 1.377 (3) | C15—C16 | 1.375 (2) |
C2—H2A | 0.9300 | C15—H15A | 0.9300 |
C3—C4 | 1.369 (3) | C16—C17 | 1.365 (3) |
C3—H3A | 0.9300 | C16—H16A | 0.9300 |
C4—C5 | 1.360 (3) | C17—C18 | 1.365 (3) |
C4—H4A | 0.9300 | C18—H18A | 0.9300 |
C5—C6 | 1.384 (3) | ||
C8—O2—C7 | 115.93 (12) | C10—C9—H9B | 111.3 |
C8—N1—C9 | 122.41 (13) | H9A—C9—H9B | 109.2 |
C8—N1—C12 | 124.27 (12) | C11—C10—C9 | 103.41 (14) |
C9—N1—C12 | 112.57 (13) | C11—C10—H10A | 111.1 |
C13—N2—C14 | 127.55 (13) | C9—C10—H10A | 111.1 |
C13—N2—H2B | 116.2 | C11—C10—H10B | 111.1 |
C14—N2—H2B | 116.2 | C9—C10—H10B | 111.1 |
C18—N3—C14 | 117.81 (14) | H10A—C10—H10B | 109.0 |
C6—C1—C2 | 118.54 (16) | C10—C11—C12 | 104.72 (14) |
C6—C1—C7 | 120.39 (16) | C10—C11—H11A | 110.8 |
C2—C1—C7 | 121.07 (16) | C12—C11—H11A | 110.8 |
C3—C2—C1 | 120.71 (17) | C10—C11—H11B | 110.8 |
C3—C2—H2A | 119.6 | C12—C11—H11B | 110.8 |
C1—C2—H2A | 119.6 | H11A—C11—H11B | 108.9 |
C4—C3—C2 | 120.37 (17) | N1—C12—C13 | 110.77 (13) |
C4—C3—H3A | 119.8 | N1—C12—C11 | 102.82 (12) |
C2—C3—H3A | 119.8 | C13—C12—C11 | 110.52 (13) |
C5—C4—C3 | 119.24 (18) | N1—C12—H12A | 110.8 |
C5—C4—H4A | 120.4 | C13—C12—H12A | 110.8 |
C3—C4—H4A | 120.4 | C11—C12—H12A | 110.8 |
C4—C5—C6 | 121.01 (18) | O3—C13—N2 | 124.20 (14) |
C4—C5—H5A | 119.5 | O3—C13—C12 | 121.48 (13) |
C6—C5—H5A | 119.5 | N2—C13—C12 | 114.25 (13) |
C1—C6—C5 | 120.13 (16) | N3—C14—C15 | 122.55 (14) |
C1—C6—H6A | 119.9 | N3—C14—N2 | 113.06 (13) |
C5—C6—H6A | 119.9 | C15—C14—N2 | 124.37 (14) |
O2—C7—C1 | 106.91 (13) | C16—C15—C14 | 118.41 (16) |
O2—C7—H7A | 110.3 | C16—C15—H15A | 120.8 |
C1—C7—H7A | 110.3 | C14—C15—H15A | 120.8 |
O2—C7—H7B | 110.3 | C17—C16—C15 | 118.72 (16) |
C1—C7—H7B | 110.3 | C17—C16—H16A | 120.6 |
H7A—C7—H7B | 108.6 | C15—C16—H16A | 120.6 |
O1—C8—N1 | 124.73 (14) | C18—C17—C16 | 119.56 (15) |
O1—C8—O2 | 124.45 (15) | C18—C17—Cl1 | 119.50 (14) |
N1—C8—O2 | 110.81 (12) | C16—C17—Cl1 | 120.94 (13) |
N1—C9—C10 | 102.49 (14) | N3—C18—C17 | 122.93 (16) |
N1—C9—H9A | 111.3 | N3—C18—H18A | 118.5 |
C10—C9—H9A | 111.3 | C17—C18—H18A | 118.5 |
N1—C9—H9B | 111.3 | ||
C6—C1—C2—C3 | 0.4 (3) | C8—N1—C12—C11 | 171.05 (14) |
C7—C1—C2—C3 | −179.33 (16) | C9—N1—C12—C11 | 0.82 (18) |
C1—C2—C3—C4 | −0.3 (3) | C10—C11—C12—N1 | −23.25 (18) |
C2—C3—C4—C5 | −0.1 (3) | C10—C11—C12—C13 | −141.51 (15) |
C3—C4—C5—C6 | 0.3 (3) | C14—N2—C13—O3 | −5.0 (3) |
C2—C1—C6—C5 | −0.2 (3) | C14—N2—C13—C12 | 172.18 (13) |
C7—C1—C6—C5 | 179.54 (17) | N1—C12—C13—O3 | −43.5 (2) |
C4—C5—C6—C1 | −0.2 (3) | C11—C12—C13—O3 | 69.8 (2) |
C8—O2—C7—C1 | 174.62 (14) | N1—C12—C13—N2 | 139.26 (13) |
C6—C1—C7—O2 | −123.60 (17) | C11—C12—C13—N2 | −107.46 (15) |
C2—C1—C7—O2 | 56.1 (2) | C18—N3—C14—C15 | −1.6 (2) |
C9—N1—C8—O1 | −9.5 (2) | C18—N3—C14—N2 | 176.92 (15) |
C12—N1—C8—O1 | −178.78 (15) | C13—N2—C14—N3 | 176.11 (14) |
C9—N1—C8—O2 | 169.35 (14) | C13—N2—C14—C15 | −5.5 (2) |
C12—N1—C8—O2 | 0.0 (2) | N3—C14—C15—C16 | 1.3 (3) |
C7—O2—C8—O1 | −5.2 (2) | N2—C14—C15—C16 | −177.01 (15) |
C7—O2—C8—N1 | 175.97 (14) | C14—C15—C16—C17 | −0.1 (3) |
C8—N1—C9—C10 | −149.02 (15) | C15—C16—C17—C18 | −0.7 (3) |
C12—N1—C9—C10 | 21.42 (19) | C15—C16—C17—Cl1 | 179.81 (14) |
N1—C9—C10—C11 | −35.11 (19) | C14—N3—C18—C17 | 0.7 (3) |
C9—C10—C11—C12 | 36.48 (19) | C16—C17—C18—N3 | 0.4 (3) |
C8—N1—C12—C13 | −70.87 (18) | Cl1—C17—C18—N3 | 179.94 (14) |
C9—N1—C12—C13 | 118.90 (15) |
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2B···O1i | 0.86 | 2.06 | 2.9148 (17) | 172 |
C6—H6A···O3ii | 0.93 | 2.39 | 3.308 (2) | 171 |
Symmetry codes: (i) x+1, y, z; (ii) −x, y+1/2, −z+3/2. |
Experimental details
Crystal data | |
Chemical formula | C18H18ClN3O3 |
Mr | 359.80 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 293 |
a, b, c (Å) | 6.2419 (14), 15.785 (4), 17.574 (4) |
V (Å3) | 1731.5 (7) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.24 |
Crystal size (mm) | 0.39 × 0.32 × 0.21 |
Data collection | |
Diffractometer | Bruker APEXII area-detector diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 22340, 3991, 3602 |
Rint | 0.021 |
(sin θ/λ)max (Å−1) | 0.651 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.032, 0.088, 1.04 |
No. of reflections | 3991 |
No. of parameters | 226 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.31, −0.17 |
Absolute structure | Flack (1983), Friedel pairs 1686 |
Absolute structure parameter | 0.02 (6) |
Computer programs: APEX2 (Bruker, 2006), SAINT (Bruker, 2006), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXTL (Bruker, 2002).
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2B···O1i | 0.86 | 2.06 | 2.9148 (17) | 172 |
C6—H6A···O3ii | 0.93 | 2.39 | 3.308 (2) | 171 |
Symmetry codes: (i) x+1, y, z; (ii) −x, y+1/2, −z+3/2. |
The title compound is an important inhibitor of peptidyl deformylase (Patel et al., 2002). Its crystal structure is presented here.
The molecular structure is shown in Fig. 1. Bond lengths and angles are normal. The dihedral angle between the C6-benzene and O1/O2/N1/C8 planes is 50.56 (7)° and that between N3-pyridine and O3/N2/C12/C13 planes is 11.34 (11)°. The crystal packing is stabilized by N—H···O and C—H···O hydrogen bonding (Table 1).