Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270199013049/gd1058sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270199013049/gd1058Isup2.hkl |
CCDC reference: 140970
The title compound was dissolved in benzene and recrystallized by slow equilibration by placing the solution inside another chamber containing hexane. Yellow crystals of appropriate size were obtained after 1–2 d.
Methyl-H atoms were riding with C—H 0.980 Å; coordinates of all other H atoms were refined.
Data collection: SMART (Siemens, 1996); cell refinement: SMART; data reduction: SHELXTL (Sheldrick, 1996); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997b); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997c); molecular graphics: XTALVIEW (McRee, 1998); software used to prepare material for publication: XTALVIEW and ZORTEP (Szolnai & Huttner, 1994).
C17H21N3O4·0.5C6H6 | Dx = 1.283 Mg m−3 |
Mr = 370.42 | Melting point = 462–463 K |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71073 Å |
a = 7.9436 (6) Å | Cell parameters from 4348 reflections |
b = 15.1440 (11) Å | θ = 1.9–27.5° |
c = 16.3075 (11) Å | µ = 0.09 mm−1 |
β = 102.2083 (13)° | T = 193 K |
V = 1917.4 (2) Å3 | Prism, clear pale yellow |
Z = 4 | 0.38 × 0.28 × 0.18 mm |
F(000) = 788 |
CCD area detector diffractometer | 4293 independent reflections |
Radiation source: rotating anode | 2898 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.035 |
ϕ and ω scans | θmax = 27.5°, θmin = 1.9° |
Absorption correction: multi-scan (SADABS; Sheldrick, 1997a) | h = −10→9 |
Tmin = 0.966, Tmax = 0.984 | k = −19→13 |
9844 measured reflections | l = −13→21 |
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) = 0.126 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.00 | w = 1/[σ2(Fo2) + (0.0578P)2 + 0.8765P] where P = (Fo2 + 2Fc2)/3 |
4293 reflections | (Δ/σ)max < 0.001 |
290 parameters | Δρmax = 0.24 e Å−3 |
0 restraints | Δρmin = −0.19 e Å−3 |
C17H21N3O4·0.5C6H6 | V = 1917.4 (2) Å3 |
Mr = 370.42 | Z = 4 |
Monoclinic, P21/n | Mo Kα radiation |
a = 7.9436 (6) Å | µ = 0.09 mm−1 |
b = 15.1440 (11) Å | T = 193 K |
c = 16.3075 (11) Å | 0.38 × 0.28 × 0.18 mm |
β = 102.2083 (13)° |
CCD area detector diffractometer | 4293 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 1997a) | 2898 reflections with I > 2σ(I) |
Tmin = 0.966, Tmax = 0.984 | Rint = 0.035 |
9844 measured reflections |
R[F2 > 2σ(F2)] = 0.045 | 0 restraints |
wR(F2) = 0.126 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.00 | Δρmax = 0.24 e Å−3 |
4293 reflections | Δρmin = −0.19 e Å−3 |
290 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 | 0.82201 (16) | 0.53883 (8) | −0.04080 (8) | 0.0305 (3) | |
C2 | 0.74440 (18) | 0.45837 (10) | −0.04234 (9) | 0.0281 (3) | |
C3 | 0.69611 (18) | 0.43084 (9) | 0.02875 (9) | 0.0272 (3) | |
C4 | 0.72940 (19) | 0.48098 (9) | 0.11071 (9) | 0.0262 (3) | |
C5 | 0.80353 (19) | 0.57202 (9) | 0.09917 (9) | 0.0281 (3) | |
C6 | 0.84404 (18) | 0.59662 (9) | 0.02617 (10) | 0.0293 (3) | |
N7 | 1.00486 (17) | 0.41198 (8) | 0.17727 (8) | 0.0329 (3) | |
C8 | 0.84202 (19) | 0.42896 (9) | 0.18283 (9) | 0.0270 (3) | |
C9 | 0.7761 (2) | 0.40134 (11) | 0.25073 (10) | 0.0345 (4) | |
C10 | 0.8807 (2) | 0.35444 (11) | 0.31458 (11) | 0.0372 (4) | |
C11 | 1.0469 (2) | 0.33625 (11) | 0.30856 (11) | 0.0379 (4) | |
C12 | 1.1061 (2) | 0.36582 (11) | 0.23976 (11) | 0.0390 (4) | |
H1 | 0.872 (2) | 0.5518 (11) | −0.0856 (11) | 0.042 (5)* | |
C21 | 0.7172 (2) | 0.41275 (13) | −0.12586 (11) | 0.0371 (4) | |
H21 | 0.595 (3) | 0.3994 (12) | −0.1474 (12) | 0.051 (5)* | |
H22 | 0.779 (3) | 0.3573 (15) | −0.1221 (13) | 0.066 (6)* | |
H23 | 0.763 (3) | 0.4496 (14) | −0.1631 (13) | 0.060 (6)* | |
N31 | 0.59848 (17) | 0.35154 (8) | 0.02884 (8) | 0.0332 (3) | |
O31 | 0.5829 (2) | 0.29810 (8) | −0.02987 (8) | 0.0584 (4) | |
O32 | 0.53097 (15) | 0.33836 (7) | 0.08920 (7) | 0.0394 (3) | |
H4 | 0.6201 (19) | 0.4886 (9) | 0.1286 (9) | 0.021 (4)* | |
C51 | 0.8293 (2) | 0.63298 (10) | 0.17129 (10) | 0.0340 (4) | |
O51 | 0.92116 (17) | 0.69786 (8) | 0.18058 (9) | 0.0536 (4) | |
O52 | 0.73982 (15) | 0.60756 (7) | 0.22847 (7) | 0.0369 (3) | |
C52 | 0.7710 (3) | 0.65554 (12) | 0.30875 (11) | 0.0470 (5) | |
H54 | 0.800 (2) | 0.7144 (14) | 0.2960 (12) | 0.056 (6)* | |
C53 | 0.9283 (3) | 0.61592 (14) | 0.36600 (14) | 0.0702 (7) | |
H51 | 1.0292 | 0.6244 | 0.3412 | 0.105* | |
H52 | 0.9096 | 0.5526 | 0.3730 | 0.105* | |
H53 | 0.9477 | 0.6451 | 0.4208 | 0.105* | |
C54 | 0.6099 (3) | 0.64728 (14) | 0.34124 (13) | 0.0647 (6) | |
H55 | 0.5142 | 0.6746 | 0.3015 | 0.097* | |
H56 | 0.6250 | 0.6771 | 0.3956 | 0.097* | |
H57 | 0.5845 | 0.5847 | 0.3480 | 0.097* | |
C61 | 0.9013 (2) | 0.68701 (10) | 0.00459 (11) | 0.0395 (4) | |
H61 | 0.8026 | 0.7193 | −0.0280 | 0.059* | |
H62 | 0.9901 | 0.6810 | −0.0286 | 0.059* | |
H63 | 0.9485 | 0.7194 | 0.0563 | 0.059* | |
H9 | 0.653 (2) | 0.4149 (11) | 0.2517 (11) | 0.040 (5)* | |
H10 | 0.839 (2) | 0.3364 (11) | 0.3623 (11) | 0.041 (5)* | |
H11 | 1.125 (3) | 0.3052 (13) | 0.3520 (12) | 0.055 (5)* | |
C121 | 1.2871 (3) | 0.34766 (18) | 0.23127 (14) | 0.0746 (8) | |
H121 | 1.2858 | 0.3226 | 0.1757 | 0.112* | |
H122 | 1.3410 | 0.3056 | 0.2746 | 0.112* | |
H123 | 1.3530 | 0.4029 | 0.2379 | 0.112* | |
C97 | −0.1339 (3) | 0.94261 (15) | −0.00152 (15) | 0.0715 (7) | |
H97 | −0.2269 | 0.9028 | −0.0028 | 0.086* | |
C98 | 0.0215 (4) | 0.92562 (16) | 0.04835 (16) | 0.0730 (7) | |
C99 | 0.1577 (4) | 0.98253 (16) | 0.05038 (16) | 0.0752 (7) | |
H98 | 0.028 (3) | 0.8737 (17) | 0.0844 (15) | 0.085 (8)* | |
H99 | 0.277 (3) | 0.9693 (16) | 0.0840 (16) | 0.089 (8)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.0309 (7) | 0.0313 (7) | 0.0293 (7) | 0.0019 (6) | 0.0065 (6) | 0.0051 (5) |
C2 | 0.0227 (7) | 0.0290 (8) | 0.0307 (8) | 0.0047 (6) | 0.0014 (6) | 0.0002 (6) |
C3 | 0.0250 (7) | 0.0242 (7) | 0.0309 (8) | 0.0010 (6) | 0.0026 (6) | −0.0018 (6) |
C4 | 0.0257 (7) | 0.0243 (7) | 0.0290 (8) | 0.0006 (6) | 0.0071 (6) | −0.0018 (6) |
C5 | 0.0261 (7) | 0.0226 (7) | 0.0344 (9) | 0.0021 (6) | 0.0041 (6) | −0.0002 (6) |
C6 | 0.0250 (8) | 0.0249 (7) | 0.0364 (9) | 0.0037 (6) | 0.0032 (7) | 0.0024 (6) |
N7 | 0.0319 (7) | 0.0359 (7) | 0.0311 (7) | 0.0061 (6) | 0.0071 (6) | 0.0071 (6) |
C8 | 0.0297 (8) | 0.0222 (7) | 0.0282 (8) | −0.0022 (6) | 0.0043 (6) | −0.0027 (6) |
C9 | 0.0343 (9) | 0.0374 (9) | 0.0331 (9) | −0.0053 (7) | 0.0097 (7) | −0.0009 (7) |
C10 | 0.0479 (10) | 0.0353 (9) | 0.0292 (9) | −0.0108 (8) | 0.0101 (8) | 0.0023 (7) |
C11 | 0.0456 (10) | 0.0330 (9) | 0.0324 (9) | 0.0024 (7) | 0.0026 (8) | 0.0073 (7) |
C12 | 0.0380 (9) | 0.0420 (10) | 0.0355 (9) | 0.0086 (8) | 0.0042 (7) | 0.0077 (7) |
C21 | 0.0357 (10) | 0.0444 (10) | 0.0305 (9) | −0.0009 (8) | 0.0051 (8) | −0.0042 (8) |
N31 | 0.0353 (7) | 0.0296 (7) | 0.0333 (8) | −0.0025 (6) | 0.0042 (6) | −0.0020 (6) |
O31 | 0.0911 (11) | 0.0418 (7) | 0.0465 (8) | −0.0254 (7) | 0.0241 (7) | −0.0209 (6) |
O32 | 0.0416 (7) | 0.0400 (7) | 0.0380 (7) | −0.0110 (5) | 0.0119 (6) | −0.0010 (5) |
C51 | 0.0302 (8) | 0.0276 (8) | 0.0429 (10) | 0.0037 (7) | 0.0046 (7) | −0.0027 (7) |
O51 | 0.0536 (8) | 0.0415 (7) | 0.0688 (9) | −0.0173 (6) | 0.0196 (7) | −0.0225 (6) |
O52 | 0.0477 (7) | 0.0311 (6) | 0.0317 (6) | 0.0003 (5) | 0.0076 (5) | −0.0057 (5) |
C52 | 0.0739 (14) | 0.0305 (9) | 0.0336 (10) | 0.0060 (9) | 0.0046 (9) | −0.0072 (7) |
C53 | 0.0929 (17) | 0.0529 (12) | 0.0504 (13) | 0.0159 (12) | −0.0177 (12) | −0.0113 (10) |
C54 | 0.0973 (17) | 0.0575 (13) | 0.0461 (12) | 0.0123 (12) | 0.0303 (12) | −0.0037 (10) |
C61 | 0.0407 (9) | 0.0291 (8) | 0.0483 (10) | 0.0004 (7) | 0.0087 (8) | 0.0068 (7) |
C121 | 0.0480 (12) | 0.120 (2) | 0.0576 (14) | 0.0380 (13) | 0.0162 (11) | 0.0396 (13) |
C97 | 0.0826 (17) | 0.0581 (14) | 0.0688 (16) | −0.0093 (12) | 0.0048 (13) | −0.0037 (12) |
C98 | 0.098 (2) | 0.0479 (13) | 0.0611 (15) | −0.0027 (13) | −0.0102 (14) | 0.0046 (11) |
C99 | 0.0777 (17) | 0.0568 (14) | 0.0779 (17) | 0.0016 (13) | −0.0134 (14) | −0.0004 (12) |
N1—C2 | 1.3634 (19) | C21—H23 | 0.95 (2) |
C2—C3 | 1.361 (2) | C51—O51 | 1.2139 (18) |
C3—C4 | 1.511 (2) | C51—O52 | 1.3430 (19) |
C4—C5 | 1.5263 (19) | O52—C52 | 1.472 (2) |
C5—C6 | 1.350 (2) | C52—C54 | 1.490 (3) |
C6—N1 | 1.381 (2) | C52—C53 | 1.516 (3) |
C3—N31 | 1.4297 (19) | C52—H54 | 0.95 (2) |
N31—O31 | 1.2397 (17) | C53—H51 | 0.9800 |
N31—O32 | 1.2327 (17) | C53—H52 | 0.9800 |
N1—H1 | 0.923 (18) | C53—H53 | 0.9800 |
C2—C21 | 1.502 (2) | C54—H55 | 0.9800 |
C4—C8 | 1.536 (2) | C54—H56 | 0.9800 |
C4—H4 | 0.980 (15) | C54—H57 | 0.9800 |
C5—C51 | 1.475 (2) | C61—H61 | 0.9800 |
C6—C61 | 1.507 (2) | C61—H62 | 0.9800 |
N7—C8 | 1.3406 (19) | C61—H63 | 0.9800 |
N7—C12 | 1.352 (2) | C121—H121 | 0.9800 |
C8—C9 | 1.386 (2) | C121—H122 | 0.9800 |
C9—C10 | 1.383 (2) | C121—H123 | 0.9800 |
C9—H9 | 1.000 (18) | C97—C98 | 1.352 (3) |
C10—C11 | 1.373 (3) | C97—C99i | 1.376 (3) |
C10—H10 | 0.949 (18) | C97—H97 | 0.9500 |
C11—C12 | 1.380 (2) | C98—C99 | 1.378 (3) |
C11—H11 | 0.96 (2) | C98—H98 | 0.98 (3) |
C12—C121 | 1.499 (3) | C99—C97i | 1.375 (3) |
C21—H21 | 0.98 (2) | C99—H99 | 1.01 (3) |
C21—H22 | 0.97 (2) | ||
C6—N1—C2 | 124.19 (14) | O31—N31—C3 | 120.89 (13) |
N1—C2—C3 | 117.76 (14) | O51—C51—O52 | 122.53 (15) |
C2—C3—C4 | 124.83 (13) | O51—C51—C5 | 125.78 (16) |
C3—C4—C5 | 110.17 (12) | O52—C51—C5 | 111.68 (13) |
C4—C5—C6 | 121.89 (13) | C51—O52—C52 | 117.50 (13) |
N1—C6—C5 | 120.56 (14) | O52—C52—C54 | 106.21 (16) |
N1—C2—C21 | 113.93 (14) | O52—C52—C53 | 108.31 (14) |
C3—C2—C21 | 128.25 (14) | C54—C52—C53 | 113.92 (18) |
C2—C3—N31 | 120.58 (13) | O52—C52—H54 | 105.7 (12) |
C4—C3—N31 | 114.50 (13) | C54—C52—H54 | 114.8 (12) |
C3—C4—C8 | 112.59 (11) | C53—C52—H54 | 107.4 (12) |
C5—C4—C8 | 112.35 (12) | C52—C53—H51 | 109.5 |
C4—C5—C51 | 117.34 (13) | C52—C53—H52 | 109.5 |
C6—C5—C51 | 120.77 (14) | H51—C53—H52 | 109.5 |
C5—C6—C61 | 126.63 (14) | C52—C53—H53 | 109.5 |
N1—C6—C61 | 112.63 (14) | H51—C53—H53 | 109.5 |
C2—N1—H1 | 116.3 (11) | H52—C53—H53 | 109.5 |
C6—N1—H1 | 119.2 (11) | C52—C54—H55 | 109.5 |
C3—C4—H4 | 108.8 (8) | C52—C54—H56 | 109.5 |
C5—C4—H4 | 108.6 (8) | H55—C54—H56 | 109.5 |
C8—C4—H4 | 104.0 (8) | C52—C54—H57 | 109.5 |
C8—N7—C12 | 118.48 (13) | H55—C54—H57 | 109.5 |
N7—C8—C9 | 121.96 (14) | H56—C54—H57 | 109.5 |
N7—C8—C4 | 117.43 (12) | C6—C61—H61 | 109.5 |
C9—C8—C4 | 120.61 (13) | C6—C61—H62 | 109.5 |
C10—C9—C8 | 119.21 (15) | H61—C61—H62 | 109.5 |
C10—C9—H9 | 121.8 (10) | C6—C61—H63 | 109.5 |
C8—C9—H9 | 119.0 (10) | H61—C61—H63 | 109.5 |
C11—C10—C9 | 118.88 (16) | H62—C61—H63 | 109.5 |
C11—C10—H10 | 120.6 (11) | C12—C121—H121 | 109.5 |
C9—C10—H10 | 120.5 (11) | C12—C121—H122 | 109.5 |
C10—C11—C12 | 119.44 (16) | H121—C121—H122 | 109.5 |
C10—C11—H11 | 121.9 (12) | C12—C121—H123 | 109.5 |
C12—C11—H11 | 118.6 (12) | H121—C121—H123 | 109.5 |
N7—C12—C11 | 122.01 (15) | H122—C121—H123 | 109.5 |
N7—C12—C121 | 117.05 (15) | C98—C97—C99i | 120.1 (2) |
C11—C12—C121 | 120.94 (16) | C98—C97—H97 | 119.9 |
C2—C21—H21 | 111.1 (11) | C99i—C97—H97 | 119.9 |
C2—C21—H22 | 111.6 (13) | C97—C98—C99 | 120.5 (2) |
H21—C21—H22 | 107.0 (17) | C97—C98—H98 | 116.2 (15) |
C2—C21—H23 | 108.0 (12) | C99—C98—H98 | 123.2 (15) |
H21—C21—H23 | 111.9 (16) | C97i—C99—C98 | 119.4 (2) |
H22—C21—H23 | 107.2 (17) | C97i—C99—H99 | 118.4 (14) |
O32—N31—O31 | 121.43 (13) | C98—C99—H99 | 122.1 (14) |
O32—N31—C3 | 117.68 (12) | ||
C6—N1—C2—C3 | −4.6 (2) | C4—C5—C6—C61 | 173.61 (14) |
N1—C2—C3—C4 | −3.0 (2) | C2—N1—C6—C61 | −168.69 (13) |
C2—C3—C4—C5 | 7.4 (2) | C12—N7—C8—C9 | 0.6 (2) |
C3—C4—C5—C6 | −5.17 (19) | C12—N7—C8—C4 | −179.60 (13) |
C4—C5—C6—N1 | −1.1 (2) | N7—C8—C9—C10 | −0.3 (2) |
C5—C6—N1—C2 | 6.7 (2) | C4—C8—C9—C10 | 179.85 (13) |
N1—C2—C3—N31 | 173.52 (12) | C8—C9—C10—C11 | −0.3 (2) |
C2—C3—N31—O31 | 13.4 (2) | C9—C10—C11—C12 | 0.7 (3) |
N1—C6—C5—C51 | 179.05 (13) | C8—N7—C12—C11 | −0.2 (2) |
C6—C5—C51—O51 | −18.4 (2) | C8—N7—C12—C121 | 179.70 (17) |
C3—C4—C8—N7 | 65.31 (17) | C10—C11—C12—N7 | −0.5 (3) |
C3—C4—C8—C9 | −114.88 (15) | C10—C11—C12—C121 | 179.66 (19) |
C5—C4—C8—N7 | −59.78 (17) | C2—C3—N31—O32 | −166.66 (13) |
C5—C4—C8—C9 | 120.03 (15) | C4—C3—N31—O32 | 10.16 (19) |
C6—N1—C2—C21 | 173.03 (14) | C4—C3—N31—O31 | −169.77 (14) |
C21—C2—C3—N31 | −3.8 (2) | C4—C5—C51—O51 | 161.76 (16) |
C21—C2—C3—C4 | 179.76 (15) | C6—C5—C51—O52 | 162.75 (13) |
N31—C3—C4—C5 | −169.31 (12) | C4—C5—C51—O52 | −17.11 (18) |
C2—C3—C4—C8 | −118.91 (15) | O51—C51—O52—C52 | −6.8 (2) |
N31—C3—C4—C8 | 64.42 (16) | C5—C51—O52—C52 | 172.16 (13) |
C8—C4—C5—C6 | 121.24 (15) | C51—O52—C52—C54 | 153.55 (15) |
C3—C4—C5—C51 | 174.69 (12) | C51—O52—C52—C53 | −83.71 (19) |
C8—C4—C5—C51 | −58.90 (17) | C99i—C97—C98—C99 | −0.5 (4) |
C51—C5—C6—C61 | −6.2 (2) | C97—C98—C99—C97i | 0.5 (4) |
Symmetry code: (i) −x, −y+2, −z. |
Experimental details
Crystal data | |
Chemical formula | C17H21N3O4·0.5C6H6 |
Mr | 370.42 |
Crystal system, space group | Monoclinic, P21/n |
Temperature (K) | 193 |
a, b, c (Å) | 7.9436 (6), 15.1440 (11), 16.3075 (11) |
β (°) | 102.2083 (13) |
V (Å3) | 1917.4 (2) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.38 × 0.28 × 0.18 |
Data collection | |
Diffractometer | CCD area detector diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 1997a) |
Tmin, Tmax | 0.966, 0.984 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 9844, 4293, 2898 |
Rint | 0.035 |
(sin θ/λ)max (Å−1) | 0.649 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.045, 0.126, 1.00 |
No. of reflections | 4293 |
No. of parameters | 290 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.24, −0.19 |
Computer programs: SMART (Siemens, 1996), SMART, SHELXTL (Sheldrick, 1996), SHELXS97 (Sheldrick, 1997b), SHELXL97 (Sheldrick, 1997c), XTALVIEW (McRee, 1998), XTALVIEW and ZORTEP (Szolnai & Huttner, 1994).
N1—C2 | 1.3634 (19) | C6—N1 | 1.381 (2) |
C2—C3 | 1.361 (2) | C3—N31 | 1.4297 (19) |
C3—C4 | 1.511 (2) | N31—O31 | 1.2397 (17) |
C4—C5 | 1.5263 (19) | N31—O32 | 1.2327 (17) |
C5—C6 | 1.350 (2) | ||
C6—N1—C2 | 124.19 (14) | C2—C3—N31 | 120.58 (13) |
N1—C2—C3 | 117.76 (14) | C4—C3—N31 | 114.50 (13) |
C2—C3—C4 | 124.83 (13) | C3—C4—C8 | 112.59 (11) |
C3—C4—C5 | 110.17 (12) | C5—C4—C8 | 112.35 (12) |
C4—C5—C6 | 121.89 (13) | C4—C5—C51 | 117.34 (13) |
N1—C6—C5 | 120.56 (14) | C6—C5—C51 | 120.77 (14) |
N1—C2—C21 | 113.93 (14) | C5—C6—C61 | 126.63 (14) |
C3—C2—C21 | 128.25 (14) | N1—C6—C61 | 112.63 (14) |
C6—N1—C2—C3 | −4.6 (2) | C2—C3—N31—O31 | 13.4 (2) |
N1—C2—C3—C4 | −3.0 (2) | N1—C6—C5—C51 | 179.05 (13) |
C2—C3—C4—C5 | 7.4 (2) | C6—C5—C51—O51 | −18.4 (2) |
C3—C4—C5—C6 | −5.17 (19) | C3—C4—C8—N7 | 65.31 (17) |
C4—C5—C6—N1 | −1.1 (2) | C3—C4—C8—C9 | −114.88 (15) |
C5—C6—N1—C2 | 6.7 (2) | C5—C4—C8—N7 | −59.78 (17) |
N1—C2—C3—N31 | 173.52 (12) | C5—C4—C8—C9 | 120.03 (15) |
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The design of cardioselective Hantzsch 1,4-dihydropyridine (DHP) L-type voltage-sensitive calcium channel agonist positive inotropes has presented a significant challenge in drug design (Langs et al., 1990, 1991). Although there have been extensive efforts to understand the molecular basis of action (Peterson et al., 1996) and structure-activity relationships (Triggle, 1996), the development of a cardioselective calcium channel stimulant has not been reported (Rampe & Kano, 1994). Recently, we discovered a novel third generation class of isomeric alkyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(pyridyl)- 5-pyridinecarboxylates where the 4-(2-pyridyl) isomer acted as a dual cardioselective calcium channel agonist/smooth muscle selective calcium channel antagonist (Iqbal et al., 1998). 1H NMR nuclear Overhauser enhancement (NOE) studies, for a group of isopropyl or phenethyl 1,4-dihydro-3-nitro-4-(3- or 6-substituted-2-pyridyl)-5-pyridinecarboxylates, clearly indicated that a significant rotamer fraction is present in which the pyridyl nitrogen atom is antiperiplanar (ap) to the 1,4-DHP H-4 in all cases irrespective of whether the substituent (H, Me, Ph) is located at the C-3 or C-6 position of the 2- pyridyl moiety. In addition, variable temperature 1H-NMR studies indicated the 1,4-DHP NH is hydrogen-bonded. The orientation of the 6-substituted-2-pyridyl group differs from that of an ortho-substituted-phenyl ring in Hantzsch 1,4-DHP calcium channel antagonists since the rotamer where the ortho-phenyl ring substituent is synperiplanar (sp) to the 1,4-DHP H-4 is generally thermodynamically more preferential (Rovnyak et al., 1991).
We now describe the X-ray analysis of racemic isopropyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(6-methyl-2-pyridyl)- pyridine-5-carboxylate, (I) (Iqbal et al., 1998), to establish the rotameric orientation of the pyridyl ring unambiguously and to determine whether a potential intramolecular hydrogen-bonding interaction involving the amine NH moiety exists. These novel third generation calcium channel modulators offer a new drug-design approach directed to the treatment of congestive heart failure, and may be useful as probes to study the structure-function relationships of calcium channels.
Each unit cell contains four molecules of the title compound and two benzene molecules of crystallization. The benzene is packed between the isopropyl groups of two neighbouring molecules of the title compound, and lies on a crystallographic centre of symmetry.
The torsion angles indicate that the 1,4 DHP ring is relatively flat; however, angles of the greatest magnitude are found around the N1 and C4 atoms. The deviation from strict planarity takes the form of a slight boat conformation with the N1 and C4 atoms being displaced towards the pyridyl side of the ring. The sum of the absolute values of all the torsion values around the 1,4 DHP ring is 28 (5)°, a value much smaller than the reported range of 39 to 78° for other 1,4-DHP ring structures (Langs & Triggle, 1985; Fossheim, 1987). Increased planarity of this ring has been suggested to be associated with greater pharmacological activity (Triggle et al., 1980; Fossheim et al., 1982).
The nitro group attached to C3 is almost coplanar with the 1,4-DHP ring, with a torsion of 13.4 (2)° relative to the C2═C3 bond. This rotation relieves the potential steric clash between the pyridyl group and the proximal oxygen of the nitro group. Similarly the ester group attached to C5 is rotated approximately 18 (2)° out of the plane of the 1,4-DHP ring. The shortness of the C3—N31 (nitro) bond [1.430 (2) Å] relative to the canonical length (1.471 Å) found in nifedipine structures indicates a greater degree of electron delocalization, this was previously observed in another nitro-substituted 1,4-DHP ring (Langs & Triggle,1 985). Similarly the N1—C2 bond is shorter than in nifedipine structures [1.363 (2) Å compared to 1.380 Å], but longer than that seen in methyl 2,6-dimethyl-5-nitro-4-(2- trifluoromethylphenyl)-1,4 dihydropyridine-3-carboxylate (1.350 Å). Despite the differences, both compounds appear to share more electron delocalization over the nitro groups which may explain the greater degree of planarity of the 1,4-DHP ring.
The pyridine group is oriented approximately perpendicular to the plane of the 1,4-DHP ring, with the nitrogen atom of the pyridyl group antiperiplanar to the 1,4-DHP H4. The pyridyl nitrogen is turned slightly toward C5 (approximately 3.7° relative to a line bisecting the C3—C4—C5 angle). No intramolecular hydrogen bond is formed between the NH of the 1,4-DHP ring and the pyridyl nitrogen since the N—H bond vector is oriented in the same direction as the pyridyl nitrogen lone pair; however, a hydrogen bond is formed between these atoms in the intermolecular packing interactions (Fig. 1). The possibility of a dimer persisting in solution similar to that found in the solid-state structure is supported by the NMR data and is worth investigating further. The ap orientation of the pyridyl nitrogen may be due to the smaller relative size of the nitrogen to the C3—H atoms; alternately, there may be an electrostatic explanation, because in the sp orientation, the pyridyl nitrogen lone pair would be approximately 3.0 Å from the nitro oxygen compared to 3.8 Å in the ap orientation.
The hydrogen positions that were defined for the methyl group attached to C2 on the 1,4-DHP ring contrast with the methyl group on C6 which does not show clearly defined hydrogen positions. The explanation for this lies in the closer approach of the nitro oxygen to the methyl at C2 (2.70 Å) relative to the ester oxygen - C6 methyl distance (2.85 Å); this shorter distance forces the H atoms to adopt a staggered conformation relative to the nitro oxygen.