Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270104012326/ga1051sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270104012326/ga1051Isup2.hkl |
CCDC reference: 245890
Compound (I) was prepared by condensation of 3-methoxy-16-(N-methyl-N-phenylaminomethylidene)oestra-1,3,5(10)-trien-17-one with guanidine hydrochoride (Matsumoto et al., 2003). The crystal used for the X-ray structure analysis was obtained by recrystallization of (I) from dichloromethane-ether-hexane(1:1:1). Analysis, found: C 75.13, H 7.48, N 12.45%; calculated for C21H25N3O: C 75.19, H 7.51, N 12.53%,
All H atoms were refined as riding on their parent atoms, with Uiso(H) values set at 1.2Ueq of the parent O and C atoms. The final difference-map peak is 1.69 Å from atom H3. The absolute configuration could not be determined from the X-ray data but was known from the synthetic route.
Data collection: CrystalClear (Rigaku, 1999); cell refinement: CrystalClear; data reduction: CrystalStructure (Rigaku/MSC, 2004); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: CRYSTALS (Watkin et al., 1996); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: CrystalStructure.
C21H25N3O | F(000) = 720.00 |
Mr = 335.45 | Dx = 1.290 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.7107 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 4940 reflections |
a = 8.198 (2) Å | θ = 3.1–27.5° |
b = 9.303 (2) Å | µ = 0.08 mm−1 |
c = 22.644 (5) Å | T = 123 K |
V = 1727.0 (6) Å3 | Prism, colourless |
Z = 4 | 0.12 × 0.10 × 0.08 mm |
Rigaku Saturn diffractometer | 2690 reflections with F2 > 2σ(F2) |
Detector resolution: 7.31 pixels mm-1 | Rint = 0.038 |
ω scans | θmax = 27.5° |
Absorption correction: multi-scan (Jacobson, 1998) | h = −10→8 |
Tmin = 0.919, Tmax = 0.994 | k = −11→10 |
14004 measured reflections | l = −29→29 |
3850 independent reflections |
Refinement on F2 | w = 1/[0.0007Fo2 + 0.5σ(Fo2)]/(4Fo2) |
R[F2 > 2σ(F2)] = 0.041 | (Δ/σ)max < 0.001 |
wR(F2) = 0.112 | Δρmax = 0.64 e Å−3 |
S = 1.01 | Δρmin = −0.58 e Å−3 |
3850 reflections | Extinction correction: Larson (1970) |
253 parameters | Extinction coefficient: 107.2 (39) |
H-atom parameters constrained |
C21H25N3O | V = 1727.0 (6) Å3 |
Mr = 335.45 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 8.198 (2) Å | µ = 0.08 mm−1 |
b = 9.303 (2) Å | T = 123 K |
c = 22.644 (5) Å | 0.12 × 0.10 × 0.08 mm |
Rigaku Saturn diffractometer | 3850 independent reflections |
Absorption correction: multi-scan (Jacobson, 1998) | 2690 reflections with F2 > 2σ(F2) |
Tmin = 0.919, Tmax = 0.994 | Rint = 0.038 |
14004 measured reflections |
R[F2 > 2σ(F2)] = 0.041 | 253 parameters |
wR(F2) = 0.112 | H-atom parameters constrained |
S = 1.01 | Δρmax = 0.64 e Å−3 |
3850 reflections | Δρmin = −0.58 e Å−3 |
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 using all reflections. The weighted R-factor (wR) and goodness of fit (S) are based on F2. R-factor (gt) are based on F. The threshold expression of F2 > 2.0 σ(F2) is used only for calculating R-factor (gt). |
x | y | z | Uiso*/Ueq | ||
O1 | 0.0736 (2) | −0.3739 (2) | 0.22700 (7) | 0.0297 (4) | |
N1 | 0.9514 (2) | 0.6197 (2) | 0.04325 (8) | 0.0234 (5) | |
N2 | 0.6604 (2) | 0.5812 (2) | 0.03685 (8) | 0.0213 (4) | |
N3 | 0.7855 (2) | 0.7799 (2) | −0.00536 (8) | 0.0275 (5) | |
C1 | 0.1463 (3) | −0.0712 (2) | 0.12471 (9) | 0.0221 (5) | |
C2 | 0.0607 (3) | −0.1765 (2) | 0.15485 (9) | 0.0231 (6) | |
C3 | 0.1427 (3) | −0.2638 (2) | 0.19481 (9) | 0.0227 (5) | |
C4 | 0.3084 (3) | −0.2449 (2) | 0.20293 (9) | 0.0226 (5) | |
C5 | 0.3946 (3) | −0.1393 (2) | 0.17243 (9) | 0.0221 (5) | |
C6 | 0.5757 (3) | −0.1293 (2) | 0.18440 (10) | 0.0284 (6) | |
C7 | 0.6647 (3) | −0.0218 (2) | 0.14596 (10) | 0.0262 (6) | |
C8 | 0.5599 (3) | 0.1102 (2) | 0.13504 (9) | 0.0206 (5) | |
C9 | 0.4081 (2) | 0.0666 (2) | 0.09916 (9) | 0.0194 (5) | |
C10 | 0.3136 (3) | −0.0485 (2) | 0.13279 (9) | 0.0204 (5) | |
C11 | 0.3055 (3) | 0.1972 (2) | 0.08000 (9) | 0.0217 (5) | |
C12 | 0.4070 (3) | 0.3193 (2) | 0.05066 (9) | 0.0222 (5) | |
C13 | 0.5497 (2) | 0.3615 (2) | 0.09065 (9) | 0.0197 (5) | |
C14 | 0.6523 (2) | 0.2252 (2) | 0.10146 (9) | 0.0206 (5) | |
C15 | 0.8181 (3) | 0.2789 (2) | 0.12501 (10) | 0.0254 (6) | |
C16 | 0.8339 (3) | 0.4160 (2) | 0.08978 (9) | 0.0223 (5) | |
C17 | 0.6823 (3) | 0.4618 (2) | 0.06789 (9) | 0.0196 (5) | |
C18 | 0.4865 (3) | 0.4335 (2) | 0.14756 (10) | 0.0274 (6) | |
C19 | 0.9657 (3) | 0.5009 (2) | 0.07590 (10) | 0.0248 (6) | |
C20 | 0.7994 (3) | 0.6558 (2) | 0.02564 (9) | 0.0209 (5) | |
C21 | −0.0993 (3) | −0.3773 (3) | 0.23098 (11) | 0.0339 (7) | |
H1 | 0.0893 | −0.0120 | 0.0975 | 0.026* | |
H2 | −0.0529 | −0.1888 | 0.1484 | 0.027* | |
H3 | 0.3647 | −0.3050 | 0.2300 | 0.027* | |
H4 | 0.5906 | −0.1026 | 0.2245 | 0.034* | |
H5 | 0.6224 | −0.2214 | 0.1779 | 0.035* | |
H6 | 0.7624 | 0.0068 | 0.1653 | 0.031* | |
H7 | 0.6907 | −0.0654 | 0.1092 | 0.032* | |
H8 | 0.5257 | 0.1484 | 0.1719 | 0.024* | |
H9 | 0.4468 | 0.0226 | 0.0640 | 0.023* | |
H10 | 0.2256 | 0.1657 | 0.0525 | 0.026* | |
H11 | 0.2529 | 0.2354 | 0.1140 | 0.026* | |
H12 | 0.4482 | 0.2864 | 0.0139 | 0.027* | |
H13 | 0.3393 | 0.4008 | 0.0444 | 0.027* | |
H14 | 0.6736 | 0.1858 | 0.0635 | 0.024* | |
H15 | 0.8149 | 0.2972 | 0.1663 | 0.030* | |
H16 | 0.9039 | 0.2134 | 0.1166 | 0.031* | |
H17 | 0.4791 | 0.5343 | 0.1415 | 0.034* | |
H18 | 0.5600 | 0.4145 | 0.1790 | 0.034* | |
H19 | 0.3818 | 0.3965 | 0.1572 | 0.034* | |
H20 | 1.0704 | 0.4742 | 0.0901 | 0.029* | |
H21 | −0.1333 | −0.3236 | 0.2645 | 0.042* | |
H22 | −0.1353 | −0.4739 | 0.2348 | 0.042* | |
H23 | −0.1450 | −0.3363 | 0.1963 | 0.042* | |
H24 | 0.6713 | 0.7930 | −0.0194 | 0.033* | |
H25 | 0.8833 | 0.8209 | −0.0194 | 0.033* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0210 (8) | 0.0271 (8) | 0.0410 (9) | −0.0004 (7) | −0.0008 (7) | 0.0123 (7) |
N1 | 0.0194 (9) | 0.0249 (9) | 0.0258 (9) | 0.0002 (8) | 0.0001 (8) | 0.0022 (8) |
N2 | 0.0188 (9) | 0.0223 (9) | 0.0228 (9) | 0.0014 (7) | −0.0001 (7) | 0.0003 (7) |
N3 | 0.0204 (9) | 0.0266 (9) | 0.0354 (10) | −0.0031 (8) | 0.0006 (8) | 0.0073 (8) |
C1 | 0.0209 (11) | 0.0205 (10) | 0.0247 (11) | 0.0036 (9) | −0.0050 (9) | −0.0012 (8) |
C2 | 0.0173 (11) | 0.0220 (10) | 0.0299 (12) | 0.0008 (9) | −0.0027 (9) | −0.0028 (9) |
C3 | 0.0245 (11) | 0.0190 (10) | 0.0247 (11) | 0.0004 (9) | 0.0017 (9) | 0.0017 (8) |
C4 | 0.0222 (12) | 0.0203 (11) | 0.0255 (11) | 0.0026 (9) | −0.0020 (9) | 0.0022 (8) |
C5 | 0.0196 (11) | 0.0240 (10) | 0.0227 (11) | 0.0019 (9) | −0.0009 (8) | −0.0006 (9) |
C6 | 0.0193 (11) | 0.0286 (11) | 0.0374 (13) | 0.0016 (10) | −0.0047 (10) | 0.0100 (10) |
C7 | 0.0183 (11) | 0.0272 (11) | 0.0331 (12) | 0.0023 (9) | −0.0007 (10) | 0.0032 (10) |
C8 | 0.0178 (10) | 0.0214 (10) | 0.0225 (10) | −0.0002 (8) | −0.0009 (8) | 0.0001 (8) |
C9 | 0.0168 (10) | 0.0211 (10) | 0.0202 (10) | 0.0002 (9) | −0.0022 (8) | 0.0002 (8) |
C10 | 0.0214 (11) | 0.0183 (10) | 0.0214 (10) | 0.0023 (9) | −0.0013 (9) | −0.0026 (8) |
C11 | 0.0160 (11) | 0.0221 (11) | 0.0270 (11) | −0.0015 (9) | −0.0043 (9) | 0.0035 (9) |
C12 | 0.0184 (10) | 0.0223 (10) | 0.0260 (11) | 0.0001 (9) | −0.0019 (9) | 0.0025 (9) |
C13 | 0.0159 (10) | 0.0195 (10) | 0.0238 (11) | −0.0000 (9) | −0.0003 (8) | 0.0002 (8) |
C14 | 0.0159 (10) | 0.0233 (10) | 0.0227 (10) | 0.0004 (9) | −0.0017 (8) | 0.0007 (8) |
C15 | 0.0175 (11) | 0.0269 (11) | 0.0318 (12) | −0.0005 (10) | −0.0040 (9) | 0.0052 (9) |
C16 | 0.0210 (11) | 0.0237 (11) | 0.0223 (10) | −0.0001 (9) | −0.0014 (9) | 0.0004 (8) |
C17 | 0.0170 (10) | 0.0204 (10) | 0.0215 (10) | −0.0002 (9) | 0.0014 (9) | −0.0027 (8) |
C18 | 0.0235 (11) | 0.0263 (11) | 0.0325 (12) | −0.0008 (9) | 0.0003 (10) | −0.0037 (10) |
C19 | 0.0160 (11) | 0.0286 (11) | 0.0298 (12) | −0.0005 (9) | −0.0012 (9) | −0.0005 (9) |
C20 | 0.0205 (11) | 0.0194 (10) | 0.0228 (10) | −0.0005 (9) | 0.0007 (9) | −0.0024 (8) |
C21 | 0.0236 (12) | 0.0378 (13) | 0.040 (1) | −0.0031 (11) | 0.0016 (11) | 0.0072 (11) |
O1—C3 | 1.379 (2) | C16—C17 | 1.404 (3) |
O1—C21 | 1.421 (3) | C16—C19 | 1.374 (3) |
N1—C19 | 1.335 (3) | N3—H24 | 0.9957 |
N1—C20 | 1.350 (3) | N3—H25 | 0.9436 |
N2—C17 | 1.326 (3) | C1—H1 | 0.9499 |
N2—C20 | 1.358 (3) | C2—H2 | 0.9500 |
N3—C20 | 1.356 (3) | C4—H3 | 0.9500 |
C1—C2 | 1.385 (3) | C6—H4 | 0.9499 |
C1—C10 | 1.400 (3) | C6—H5 | 0.9500 |
C2—C3 | 1.390 (3) | C7—H6 | 0.9500 |
C3—C4 | 1.381 (3) | C7—H7 | 0.9500 |
C4—C5 | 1.394 (3) | C8—H8 | 0.9500 |
C5—C6 | 1.512 (3) | C9—H9 | 0.9500 |
C5—C10 | 1.400 (3) | C11—H10 | 0.9500 |
C6—C7 | 1.513 (3) | C11—H11 | 0.9501 |
C7—C8 | 1.519 (3) | C12—H12 | 0.9499 |
C8—C9 | 1.540 (3) | C12—H13 | 0.9500 |
C8—C14 | 1.515 (3) | C14—H14 | 0.9501 |
C9—C10 | 1.525 (3) | C15—H15 | 0.9499 |
C9—C11 | 1.540 (3) | C15—H16 | 0.9500 |
C11—C12 | 1.557 (3) | C18—H17 | 0.9500 |
C12—C13 | 1.531 (3) | C18—H18 | 0.9500 |
C13—C14 | 1.541 (3) | C18—H19 | 0.9500 |
C13—C17 | 1.523 (3) | C19—H20 | 0.9500 |
C13—C18 | 1.542 (3) | C21—H21 | 0.9499 |
C14—C15 | 1.544 (3) | C21—H22 | 0.9500 |
C15—C16 | 1.510 (3) | C21—H23 | 0.9499 |
O1—C3—C2 | 125.4 (2) | H25—N3—H24 | 129.9485 |
O1—C3—C4 | 115.4 (2) | C1—C2—H2 | 120.4231 |
C21—O1—C3 | 117.4 (2) | H1—C1—C2 | 118.7730 |
N2—C17—C13 | 126.6 (2) | H1—C1—C10 | 118.6300 |
N2—C17—C16 | 124.1 (2) | H2—C2—C3 | 120.2725 |
C20—N2—C17 | 114.4 (2) | C3—C4—H3 | 119.2854 |
N2—C20—N1 | 126.3 (2) | H3—C4—C5 | 119.2198 |
N2—C20—N3 | 117.4 (2) | C5—C6—H4 | 108.2917 |
N1—C19—C16 | 122.2 (2) | C5—C6—H5 | 108.1867 |
C20—N1—C19 | 116.8 (2) | H4—C6—C7 | 108.3790 |
N1—C20—N3 | 116.2 (2) | H5—C6—C7 | 108.1847 |
C1—C2—C3 | 119.3 (2) | C6—C7—H6 | 109.0701 |
C10—C1—C2 | 122.6 (2) | C6—C7—H7 | 109.2664 |
C1—C10—C5 | 117.2 (2) | H5—C6—H4 | 109.4631 |
C1—C10—C9 | 122.6 (2) | H6—C7—C8 | 108.9874 |
C2—C3—C4 | 119.2 (2) | H7—C7—C8 | 109.2436 |
C3—C4—C5 | 121.5 (2) | C7—C8—H8 | 109.0585 |
C4—C5—C10 | 120.2 (2) | H7—C7—H6 | 109.4672 |
C4—C5—C6 | 116.9 (2) | C8—C9—H9 | 106.6153 |
C10—C5—C6 | 122.9 (2) | H8—C8—C9 | 108.8839 |
C5—C6—C7 | 114.3 (2) | H8—C8—C14 | 108.9288 |
C5—C10—C9 | 120.2 (2) | C8—C14—H14 | 105.8929 |
C6—C7—C8 | 110.8 (2) | H9—C9—C10 | 106.6012 |
C7—C8—C9 | 109.3 (2) | H9—C9—C11 | 106.6114 |
C7—C8—C14 | 111.7 (2) | C9—C11—H10 | 108.5447 |
C8—C9—C10 | 109.4 (2) | C9—C11—H11 | 108.3389 |
C8—C9—C11 | 112.5 (2) | C11—C12—H12 | 109.2523 |
C14—C8—C9 | 109.0 (2) | C11—C12—H13 | 109.5181 |
C8—C14—C13 | 112.8 (2) | H10—C11—C12 | 108.2864 |
C8—C14—C15 | 119.7 (2) | H11—C11—C12 | 108.3491 |
C11—C9—C10 | 114.6 (2) | H11—C11—H10 | 109.4626 |
C9—C11—C12 | 113.8 (2) | H12—C12—C13 | 109.2209 |
C11—C12—C13 | 110.1 (2) | H13—C12—C13 | 109.3073 |
C12—C13—C17 | 120.2 (2) | H13—C12—H12 | 109.4591 |
C12—C13—C18 | 110.4 (2) | C13—C14—H14 | 105.8954 |
C12—C13—C14 | 107.5 (2) | C13—C18—H17 | 109.2299 |
C17—C13—C14 | 99.7 (2) | C13—C18—H18 | 109.4164 |
C18—C13—C14 | 114.1 (2) | C13—C18—H19 | 109.7766 |
C13—C14—C15 | 105.6 (2) | H14—C14—C15 | 105.9498 |
C13—C17—C16 | 109.0 (2) | C14—C15—H15 | 111.9072 |
C18—C13—C17 | 104.8 (2) | C14—C15—H16 | 111.9685 |
C14—C15—C16 | 99.6 (2) | H15—C15—C16 | 111.7858 |
C15—C16—C17 | 111.6 (2) | H16—C15—C16 | 111.8937 |
C15—C16—C19 | 132.3 (2) | H16—C15—H15 | 109.4574 |
C19—C16—C17 | 116.1 (2) | C16—C19—H20 | 118.8644 |
O1—C21—H21 | 109.3545 | H18—C18—H17 | 109.4726 |
O1—C21—H22 | 109.6639 | H19—C18—H17 | 109.4680 |
O1—C21—H23 | 109.3960 | H19—C18—H18 | 109.4633 |
N1—C19—H20 | 118.9273 | H22—C21—H21 | 109.4703 |
H24—N3—C20 | 110.3702 | H23—C21—H21 | 109.4644 |
H25—N3—C20 | 116.5734 | H23—C21—H22 | 109.4780 |
C21—O1—C3—C2 | −16.1 (3) | C9—C8—C14—C15 | −174.7 (2) |
C21—O1—C3—C4 | 165.9 (2) | C8—C9—C10—C1 | 155.2 (2) |
C20—N1—C19—C16 | 1.9 (3) | C8—C9—C10—C5 | −26.6 (2) |
C19—N1—C20—N2 | −1.5 (3) | C11—C9—C10—C1 | 27.8 (3) |
C19—N1—C20—N3 | 177.3 (2) | C11—C9—C10—C5 | −154.0 (2) |
C20—N2—C17—C13 | 175.7 (2) | C8—C9—C11—C12 | 49.2 (2) |
C20—N2—C17—C16 | 2.2 (3) | C10—C9—C11—C12 | 174.9 (2) |
C17—N2—C20—N1 | −0.4 (3) | C9—C11—C12—C13 | −52.7 (2) |
C17—N2—C20—N3 | −179.3 (2) | C11—C12—C13—C14 | 57.6 (2) |
C10—C1—C2—C3 | −0.0 (3) | C11—C12—C13—C17 | 170.5 (2) |
C2—C1—C10—C5 | 1.1 (3) | C11—C12—C13—C18 | −67.4 (2) |
C2—C1—C10—C9 | 179.4 (2) | C12—C13—C14—C8 | −64.2 (2) |
C1—C2—C3—O1 | −178.9 (2) | C12—C13—C14—C15 | 163.3 (2) |
C1—C2—C3—C4 | −0.9 (3) | C17—C13—C14—C8 | 169.8 (2) |
O1—C3—C4—C5 | 178.9 (2) | C17—C13—C14—C15 | 37.2 (2) |
C2—C3—C4—C5 | 0.7 (3) | C18—C13—C14—C8 | 58.6 (2) |
C3—C4—C5—C6 | −179.4 (2) | C18—C13—C14—C15 | −73.9 (2) |
C3—C4—C5—C10 | 0.5 (3) | C12—C13—C17—N2 | 43.7 (3) |
C4—C5—C6—C7 | 174.8 (2) | C12—C13—C17—C16 | −142.0 (2) |
C10—C5—C6—C7 | −5.2 (3) | C14—C13—C17—N2 | 160.5 (2) |
C4—C5—C10—C1 | −1.4 (3) | C14—C13—C17—C16 | −25.1 (2) |
C4—C5—C10—C9 | −179.7 (2) | C18—C13—C17—N2 | −81.2 (2) |
C6—C5—C10—C1 | 178.6 (2) | C18—C13—C17—C16 | 93.2 (2) |
C6—C5—C10—C9 | 0.2 (3) | C8—C14—C15—C16 | −163.6 (2) |
C5—C6—C7—C8 | 37.0 (2) | C13—C14—C15—C16 | −35.1 (2) |
C6—C7—C8—C9 | −64.7 (2) | C14—C15—C16—C17 | 19.6 (2) |
C6—C7—C8—C14 | 174.7 (2) | C14—C15—C16—C19 | −160.5 (2) |
C7—C8—C9—C10 | 58.1 (2) | C15—C16—C17—N2 | 178.1 (2) |
C7—C8—C9—C11 | −173.3 (2) | C15—C16—C17—C13 | 3.6 (2) |
C14—C8—C9—C10 | −179.6 (2) | C19—C16—C17—N2 | −1.9 (3) |
C14—C8—C9—C11 | −51.1 (2) | C19—C16—C17—C13 | −176.4 (2) |
C7—C8—C14—C13 | −179.0 (2) | C15—C16—C19—N1 | 179.7 (2) |
C7—C8—C14—C15 | −53.9 (2) | C17—C16—C19—N1 | −0.3 (3) |
C9—C8—C14—C13 | 60.1 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H24···N1i | 1.00 | 2.05 | 3.019 (3) | 164 |
N3—H25···N2ii | 0.94 | 2.48 | 3.409 (3) | 169 |
Symmetry codes: (i) x−1/2, −y+3/2, −z; (ii) x+1/2, −y+3/2, −z. |
Experimental details
Crystal data | |
Chemical formula | C21H25N3O |
Mr | 335.45 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 123 |
a, b, c (Å) | 8.198 (2), 9.303 (2), 22.644 (5) |
V (Å3) | 1727.0 (6) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.08 |
Crystal size (mm) | 0.12 × 0.10 × 0.08 |
Data collection | |
Diffractometer | Rigaku Saturn diffractometer |
Absorption correction | Multi-scan (Jacobson, 1998) |
Tmin, Tmax | 0.919, 0.994 |
No. of measured, independent and observed [F2 > 2σ(F2)] reflections | 14004, 3850, 2690 |
Rint | 0.038 |
(sin θ/λ)max (Å−1) | 0.649 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.041, 0.112, 1.01 |
No. of reflections | 3850 |
No. of parameters | 253 |
No. of restraints | ? |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.64, −0.58 |
Computer programs: CrystalClear (Rigaku, 1999), CrystalClear, CrystalStructure (Rigaku/MSC, 2004), SIR97 (Altomare et al., 1999), CRYSTALS (Watkin et al., 1996), PLATON (Spek, 2003), CrystalStructure.
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H24···N1i | 1.00 | 2.05 | 3.019 (3) | 164 |
N3—H25···N2ii | 0.94 | 2.48 | 3.409 (3) | 169 |
Symmetry codes: (i) x−1/2, −y+3/2, −z; (ii) x+1/2, −y+3/2, −z. |
Over the years, several steroidal derivatives with an additional ring (E) fused at either the C2,3 or the C16,17 positions have been prepared (Siddiqui et al., 1995; Camoutsis, 1996; Singh & Singh, 1999). These compounds exhibit a variety of biological properties, such as steroidal receptor antagonistic activity and/or antiinflammatory activity. The title compound, (I), was synthesized in order to study the influence of ring annelation of aminopyrimidine to the oestrane framework on the binding affinity to the oestrogen receptor (ERα). Furthermore, a number of tripeptides have been linked to the amine group as potential ligands for 99m-technetium or 186-rhenium and 188-rhenium radionuclides (Matsumoto et al., 2003). These compounds are to be assayed as potential radiodiagnostics, e.g. for minimal oestrogen positive breast cancer. \sch
In order to investigate the conformation of (I) as the steroid component of these oestrane-tripeptide hybrids, an X-ray structural analysis was carried out. There is one independent molecule per asymmetric unit (Fig. 1). Ring A shows little distortion from planarity, as is evident in other oestrones and oestradiols for which X-ray crystal structural analyses have been carried out. Ring C, with trans fusion to rings B and D, has a chair conformation. As a cyclohexene, ring B in oestranes is usually conformationally more flexible (Bucourt & Hainault, 1967; Yamamoto et al., 2004). In (I), ring B has an envelope conformation, as characterized by the Cremer & Pople (1975) puckering parameters Q = 0.533 (2) Å, θ = 52.0 (3)° and ϕ = 172.1 (3)° [for a perfect envelope conformation, θ = 54.7° and ϕ = k × 60°; for a perfect half-chair conformation (the next closest conformation), θ = 50.8° and ϕ = k × 60° + 30° (Boeyens, 1978)]. This configuration is also in accordance with the relative signs of the endocyclic torsion angles within ring B (see Boeyens, 1978).
Ring D has an envelope conformation [Q = 0.378 (2) Å and ϕ = 211.0 (3)°], with atom C14 as the flap, a pseudorotation angle Δ = 12.8 (2)° and a maximum torsion angle ϕm = 38.2 (1)° (Rao et al., 1981) for the atom sequence C13—C17. The aminopyrimidine ring shows a minor distortion from planarity [C16—C19—N1···N3 torsion angle 4.7 (4)°], which may be due to the hydrogen bonding involving both atom N1 and one of the H atoms on N3 (see below). While the C19—N1 [1.335 (3) Å] and C17—N2 [1.326 (3) Å] bond distances, as well as the N1—C20 [1.350 (3) Å] and N2—C20 [1.358 (3) Å] bond distances, are similar to one another and to the corresponding bond lengths found in the parent compound 2-aminopyrimidine (Furberg et al., 1979), the C16—C17 bond length [1.404 (3) Å] is longer than both the corresponding bond length in 2-aminopyrimidine (Furberg et al., 1979) and the corresponding typical bond lengths found in 16,17-unsaturated steroids, e.g., in 5α-androst-16-en-3-one (1.302 Å; Cox & Turner, 1984) and in 17-(3-oxazolin-4-yl)androsta-4,16-dien-3-one (1.342 Å; Meetsma et al., 1993). These differences may be rationalized by taking into account that a hydrogen bond to N1 as donor favours the iminodiazacyclohexadiene ring having a single bond at C16—C17 over other resonance forms for the aminopyrimidine unit.
In the crystal structure (Fig. 2), molecules of (I) pack in chains of two rows of molecules, where parallel chains are arranged in a stepwise fashion. Another arrangement of parallel chains, tilted by 81.02 (7)°, is also ordered in a stepwise fashion. The governing factor is the hydrogen bond formed by the amine group of the aminopyrimidine moiety with one of the pyrimidine N atoms of a neighbouring molecule. It is clear from the X-ray data that only one H atom of the amine group bound to atom C20 forms a strong hydrogen bond with one adjacent atom, N1 (Table 1). The N3—H25···N2ii interaction is weaker, with an H25···N2 distance of 2.48 Å (Table 1).
From an AM1 calculation of the pyrimidine fragment of I1), it is evident that the electrostatic potential at atom N1 (−0.310) is higher than that at the other N atoms, especially at atom N2 (−0.273 for N2 and −0.235 for the NH2 N atom). This result strongly suggests that any protic interaction will take place predominantely at atom N1. This fact is not only important in evaluating the crystal structure of (I), but can also be used to argue the possible conformations of (I)-tripeptide hybrids.
The arrangement of molecules of (I) in the crystal forces neighbouring molecules on the same side of the chain to lie close together, as shown by the intermolecular contacts (Table 1).