Crystal structure and Hirshfeld surface analysis of a salt of anti­neoplastic kinase inhibitor vandetanib

A salt of vandetanib, namely, 4-({4-[(4-bromo-2-fluoro­phen­yl)amino]-6-meth­oxy­quinazolin-7-yl}meth­oxy)-1-methyl­piperazin-1-ium 2-(butyl­amino)-4-phen­oxy-6-sulfamoylbenzoate aceto­nitrile monosolvate, C₂₂H₂₅BrFN₄O₂⁺·C₁₇H₁₉N₂O₅S⁻·C₂H₃N, com­posed of kinase inhibitor vandetanib and sulfamyl diuretic bumetanide in a 1:1 molar ratio, is reported. There is proton transfer between the piperidine ring of vandetanib and the carboxyl group of bumetanide to form the salt. In the vandetanib cation, the arene and pyrimidine rings are not coplanar, their planes subtending a dihedral angle of 60.47 (14)°. The roles of the inter­molecular inter­actions in the crystal packing were clarified using Hirshfeld surface analysis, and two-dimensional fingerprint plots indicate that the most important contributions to the crystal packing are from H...H (40.5%), O...H/H...C (20.7%), C...H/ H...C (18.8%) and N...C/C...N (9.0%) contacts.

Computing details

4-({4-[(4-Bromo-2-fluorophenyl)amino]-6-methoxyquinazolin-7-yl}methoxy)-1-methylpiperazin-1-ium 2-(butylamino)-4-phenoxy-6-sulfamoylbenzoate acetonitrile monosolvate

Crystal data

C22H25BrFN4O2^+·C17H19N2O5S^−·C2H3N	Z = 2
Mr = 880.82	F(000) = 916
Triclinic, P1	Dx = 1.410 Mg m^−3
a = 12.5755 (3) Å	Cu Kα radiation, λ = 1.54184 Å
b = 12.6649 (3) Å	Cell parameters from 10183 reflections
c = 14.4336 (2) Å	θ = 3.3–75.7°
α = 68.909 (2)°	µ = 2.34 mm^−1
β = 82.733 (2)°	T = 200 K
γ = 75.557 (2)°	Block, clear light colourless
V = 2075.30 (8) Å^3	0.15 × 0.13 × 0.11 mm

Data collection

XtaLAB Synergy R, DW system, HyPix diffractometer	8229 independent reflections
Mirror monochromator	6803 reflections with I > 2σ(I)
Detector resolution: 10.0000 pixels mm^-1	Rint = 0.041
ω scans	θmax = 76.5°, θmin = 3.3°
Absorption correction: multi-scan (CrysAlis PRO; Rigaku OD, 2022)	h = −13→15
Tmin = 0.650, Tmax = 1.000	k = −15→15
23536 measured reflections	l = −17→18

Refinement

Refinement on F^2	Primary atom site location: iterative
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.053	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.156	w = 1/[σ^2(Fo^2) + (0.0823P)^2 + 1.8341P] where P = (Fo^2 + 2Fc^2)/3
S = 1.05	(Δ/σ)max = 0.001
8229 reflections	Δρmax = 1.37 e Å^−3
539 parameters	Δρmin = −0.69 e Å^−3
0 restraints

Special details

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
Br1	0.67091 (4)	1.46322 (4)	0.55377 (3)	0.06337 (16)
F1	0.90103 (16)	1.06014 (18)	0.56148 (14)	0.0496 (5)
O6	0.9323 (2)	0.8108 (2)	0.17554 (16)	0.0459 (5)
O7	0.94456 (17)	0.59723 (18)	0.28619 (15)	0.0365 (4)
N3	0.7903 (2)	1.0507 (2)	0.40976 (17)	0.0320 (5)
H3	0.807061	1.069170	0.345666	0.038*
N4	0.76464 (19)	0.9065 (2)	0.55885 (17)	0.0328 (5)
N5	0.8055 (2)	0.7049 (2)	0.57422 (17)	0.0354 (5)
N6	0.95552 (19)	0.2753 (2)	0.14596 (18)	0.0300 (5)
H6	0.889 (4)	0.269 (4)	0.154 (3)	0.052 (11)*
C18	0.7067 (3)	1.3330 (3)	0.5111 (2)	0.0429 (7)
C19	0.6480 (3)	1.3332 (3)	0.4356 (2)	0.0409 (7)
H19	0.591302	1.397893	0.404936	0.049*
C20	0.6741 (2)	1.2371 (3)	0.4062 (2)	0.0358 (6)
H20	0.633732	1.235840	0.355338	0.043*
C21	0.7573 (2)	1.1427 (2)	0.44869 (19)	0.0317 (6)
C22	0.8149 (3)	1.1470 (3)	0.5229 (2)	0.0367 (6)
C23	0.7897 (3)	1.2409 (3)	0.5549 (2)	0.0434 (7)
H23	0.829240	1.241816	0.606359	0.052*
C24	0.7980 (2)	0.9368 (2)	0.46350 (19)	0.0284 (5)
C25	0.8389 (2)	0.8517 (2)	0.41621 (19)	0.0286 (5)
C26	0.8414 (2)	0.7361 (2)	0.4753 (2)	0.0305 (5)
C27	0.7704 (2)	0.7918 (3)	0.6073 (2)	0.0353 (6)
H27	0.745294	0.771358	0.675044	0.042*
C28	0.8724 (2)	0.8789 (2)	0.3139 (2)	0.0309 (6)
H28	0.872058	0.956977	0.273468	0.037*
C29	0.9052 (2)	0.7924 (3)	0.2739 (2)	0.0319 (6)
C30	0.9103 (2)	0.6745 (2)	0.3346 (2)	0.0313 (6)
C31	0.8797 (2)	0.6469 (2)	0.4339 (2)	0.0327 (6)
H31	0.884361	0.568131	0.474730	0.039*
C32	0.8885 (5)	0.9218 (4)	0.1080 (3)	0.0732 (14)
H32A	0.810501	0.945709	0.125215	0.110*
H32B	0.896514	0.919108	0.040431	0.110*
H32C	0.928208	0.977652	0.111551	0.110*
C33	0.9330 (2)	0.4798 (2)	0.3374 (2)	0.0329 (6)
H33A	0.855364	0.478224	0.359140	0.039*
H33B	0.978512	0.443442	0.396675	0.039*
C34	0.9713 (2)	0.4156 (2)	0.2642 (2)	0.0287 (5)
H34	1.049267	0.420449	0.242716	0.034*
C35	0.9031 (2)	0.4671 (3)	0.1723 (2)	0.0333 (6)
H35A	0.904744	0.550146	0.139879	0.040*
H35B	0.825777	0.461598	0.191882	0.040*
C36	0.9473 (2)	0.4033 (2)	0.0993 (2)	0.0315 (6)
H36A	0.898277	0.434511	0.042577	0.038*
H36B	1.020925	0.417766	0.073219	0.038*
C37	1.0150 (2)	0.2235 (2)	0.2405 (2)	0.0324 (6)
H37A	1.093516	0.226082	0.225712	0.039*
H37B	1.010312	0.141157	0.271879	0.039*
C38	0.9672 (2)	0.2877 (2)	0.3122 (2)	0.0321 (6)
H38A	1.009571	0.252661	0.373374	0.039*
H38B	0.890098	0.280650	0.330846	0.039*
C39	1.0067 (3)	0.2172 (3)	0.0731 (2)	0.0404 (7)
H39A	1.009036	0.133850	0.102893	0.061*
H39B	1.081577	0.229307	0.054918	0.061*
H39C	0.963133	0.250061	0.013543	0.061*
S1	0.69507 (5)	0.65651 (6)	0.97649 (5)	0.03338 (17)
O1	0.7221 (2)	0.7233 (2)	1.02794 (17)	0.0484 (6)
O2	0.78010 (16)	0.6105 (2)	0.91622 (18)	0.0454 (5)
O3	0.26954 (16)	0.68389 (18)	0.93466 (16)	0.0391 (5)
O4	0.21762 (15)	0.83186 (18)	0.79706 (14)	0.0341 (4)
O5	0.70675 (14)	0.87738 (16)	0.81418 (14)	0.0284 (4)
N1	0.6492 (2)	0.5500 (3)	1.0531 (2)	0.0413 (6)
H1A	0.667 (3)	0.486 (4)	1.041 (3)	0.045 (10)*
H1B	0.601 (4)	0.566 (4)	1.090 (4)	0.071 (15)*
N2	0.55352 (19)	1.0113 (2)	0.67886 (19)	0.0371 (5)
H2	0.622464	1.017569	0.671753	0.044*
C1	0.5861 (2)	0.7474 (2)	0.89793 (19)	0.0274 (5)
C2	0.4838 (2)	0.7193 (2)	0.90942 (19)	0.0276 (5)
H2A	0.470755	0.649943	0.959246	0.033*
C3	0.4009 (2)	0.7946 (2)	0.84654 (19)	0.0265 (5)
C4	0.4219 (2)	0.8931 (2)	0.77032 (19)	0.0279 (5)
H4	0.364685	0.943227	0.727626	0.033*
C5	0.5260 (2)	0.9198 (2)	0.75542 (19)	0.0279 (5)
C6	0.6053 (2)	0.8477 (2)	0.82435 (19)	0.0259 (5)
C7	0.2887 (2)	0.7672 (2)	0.8607 (2)	0.0281 (5)
C8	0.7085 (2)	0.9688 (2)	0.8463 (2)	0.0287 (5)
C9	0.6389 (3)	0.9926 (3)	0.9218 (3)	0.0435 (7)
H9	0.585001	0.948438	0.952434	0.052*
C10	0.6489 (3)	1.0820 (3)	0.9522 (3)	0.0507 (8)
H10	0.600481	1.099922	1.003214	0.061*
C11	0.7283 (3)	1.1451 (3)	0.9089 (3)	0.0481 (8)
H11	0.735241	1.205418	0.930707	0.058*
C12	0.7976 (3)	1.1199 (3)	0.8339 (3)	0.0451 (7)
H12	0.852416	1.162907	0.803943	0.054*
C13	0.7872 (2)	1.0316 (3)	0.8021 (2)	0.0350 (6)
H13	0.834396	1.014837	0.750001	0.042*
C14	0.4764 (3)	1.0987 (3)	0.6087 (2)	0.0405 (7)
H14A	0.428723	1.060725	0.587578	0.049*
H14B	0.517290	1.140348	0.549029	0.049*
C15	0.4046 (3)	1.1863 (3)	0.6551 (3)	0.0599 (10)
H15A	0.350000	1.241230	0.606449	0.072*
H15B	0.363528	1.143640	0.714063	0.072*
C16	0.4657 (4)	1.2545 (4)	0.6859 (4)	0.0672 (11)
H16A	0.505029	1.299949	0.627186	0.081*
H16B	0.520978	1.200671	0.734338	0.081*
C17	0.3891 (5)	1.3354 (5)	0.7321 (4)	0.0852 (15)
H17A	0.334052	1.388443	0.684379	0.128*
H17B	0.431030	1.380109	0.750309	0.128*
H17C	0.352130	1.290236	0.791745	0.128*
N7	0.5526 (5)	0.4934 (7)	0.8103 (6)	0.147 (3)
C40	0.7623 (5)	0.4550 (5)	0.7872 (4)	0.0795 (14)
H40A	0.794289	0.451720	0.847001	0.119*
H40B	0.783664	0.517287	0.729771	0.119*
H40C	0.789371	0.380741	0.776201	0.119*
C41	0.6450 (6)	0.4773 (6)	0.8000 (4)	0.0929 (19)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Br1	0.0945 (3)	0.0491 (2)	0.0617 (3)	−0.0288 (2)	0.0219 (2)	−0.0364 (2)
F1	0.0553 (11)	0.0514 (11)	0.0438 (10)	−0.0098 (9)	−0.0118 (8)	−0.0165 (9)
O6	0.0671 (15)	0.0393 (12)	0.0308 (10)	−0.0120 (11)	0.0130 (10)	−0.0163 (9)
O7	0.0463 (11)	0.0309 (10)	0.0367 (10)	−0.0104 (9)	0.0051 (9)	−0.0176 (9)
N3	0.0442 (13)	0.0302 (12)	0.0245 (10)	−0.0100 (10)	0.0034 (9)	−0.0131 (9)
N4	0.0367 (12)	0.0346 (13)	0.0286 (11)	−0.0094 (10)	0.0027 (9)	−0.0130 (10)
N5	0.0458 (14)	0.0334 (13)	0.0282 (11)	−0.0108 (11)	−0.0003 (10)	−0.0108 (10)
N6	0.0234 (11)	0.0359 (13)	0.0374 (12)	−0.0104 (9)	0.0025 (9)	−0.0191 (10)
C18	0.061 (2)	0.0356 (16)	0.0392 (16)	−0.0231 (15)	0.0185 (14)	−0.0191 (13)
C19	0.0459 (17)	0.0356 (16)	0.0420 (16)	−0.0136 (13)	0.0108 (13)	−0.0151 (13)
C20	0.0416 (15)	0.0338 (15)	0.0346 (14)	−0.0144 (12)	0.0046 (12)	−0.0128 (12)
C21	0.0405 (15)	0.0319 (14)	0.0254 (12)	−0.0160 (12)	0.0070 (11)	−0.0103 (11)
C22	0.0472 (16)	0.0360 (15)	0.0289 (13)	−0.0162 (13)	0.0011 (12)	−0.0098 (12)
C23	0.061 (2)	0.0467 (18)	0.0312 (14)	−0.0247 (16)	0.0071 (13)	−0.0176 (13)
C24	0.0273 (12)	0.0316 (14)	0.0278 (12)	−0.0078 (10)	−0.0006 (10)	−0.0113 (11)
C25	0.0284 (12)	0.0328 (14)	0.0277 (12)	−0.0075 (11)	−0.0002 (10)	−0.0139 (11)
C26	0.0300 (13)	0.0329 (14)	0.0282 (13)	−0.0060 (11)	−0.0033 (10)	−0.0098 (11)
C27	0.0405 (15)	0.0360 (15)	0.0270 (13)	−0.0086 (12)	0.0018 (11)	−0.0089 (11)
C28	0.0352 (14)	0.0302 (14)	0.0291 (13)	−0.0119 (11)	0.0026 (11)	−0.0105 (11)
C29	0.0336 (14)	0.0366 (15)	0.0279 (13)	−0.0105 (12)	0.0027 (10)	−0.0132 (11)
C30	0.0307 (13)	0.0322 (14)	0.0364 (14)	−0.0071 (11)	−0.0003 (11)	−0.0185 (12)
C31	0.0372 (14)	0.0287 (14)	0.0331 (14)	−0.0063 (11)	−0.0044 (11)	−0.0112 (11)
C32	0.131 (4)	0.047 (2)	0.0298 (17)	−0.008 (2)	0.014 (2)	−0.0132 (16)
C33	0.0368 (14)	0.0295 (14)	0.0337 (14)	−0.0062 (11)	−0.0001 (11)	−0.0134 (11)
C34	0.0274 (12)	0.0291 (14)	0.0316 (13)	−0.0054 (10)	−0.0019 (10)	−0.0131 (11)
C35	0.0324 (14)	0.0308 (14)	0.0367 (14)	−0.0016 (11)	−0.0064 (11)	−0.0132 (12)
C36	0.0318 (13)	0.0335 (14)	0.0310 (13)	−0.0086 (11)	−0.0050 (11)	−0.0110 (11)
C37	0.0338 (14)	0.0290 (14)	0.0347 (14)	−0.0078 (11)	−0.0009 (11)	−0.0110 (11)
C38	0.0335 (14)	0.0318 (14)	0.0306 (13)	−0.0086 (11)	0.0016 (11)	−0.0102 (11)
C39	0.0385 (15)	0.0475 (18)	0.0434 (16)	−0.0118 (13)	0.0062 (13)	−0.0262 (14)
S1	0.0252 (3)	0.0334 (4)	0.0369 (3)	−0.0073 (3)	−0.0053 (2)	−0.0045 (3)
O1	0.0534 (13)	0.0492 (13)	0.0456 (12)	−0.0212 (11)	−0.0196 (10)	−0.0073 (10)
O2	0.0251 (10)	0.0432 (12)	0.0543 (13)	−0.0019 (9)	0.0035 (9)	−0.0060 (10)
O3	0.0309 (10)	0.0341 (11)	0.0458 (12)	−0.0141 (8)	−0.0005 (9)	−0.0015 (9)
O4	0.0276 (9)	0.0439 (12)	0.0308 (9)	−0.0135 (8)	−0.0028 (8)	−0.0085 (9)
O5	0.0225 (8)	0.0325 (10)	0.0349 (9)	−0.0116 (7)	0.0043 (7)	−0.0148 (8)
N1	0.0384 (14)	0.0341 (15)	0.0422 (15)	−0.0066 (11)	−0.0002 (12)	−0.0036 (12)
N2	0.0269 (11)	0.0375 (13)	0.0381 (13)	−0.0115 (10)	0.0014 (9)	−0.0007 (11)
C1	0.0251 (12)	0.0278 (13)	0.0295 (12)	−0.0052 (10)	−0.0011 (10)	−0.0106 (10)
C2	0.0274 (12)	0.0264 (13)	0.0302 (13)	−0.0108 (10)	0.0020 (10)	−0.0088 (10)
C3	0.0266 (12)	0.0287 (13)	0.0283 (12)	−0.0107 (10)	0.0018 (10)	−0.0127 (11)
C4	0.0274 (12)	0.0297 (13)	0.0277 (12)	−0.0081 (10)	−0.0039 (10)	−0.0090 (11)
C5	0.0287 (13)	0.0269 (13)	0.0278 (12)	−0.0093 (10)	0.0031 (10)	−0.0082 (10)
C6	0.0218 (11)	0.0279 (13)	0.0314 (12)	−0.0081 (10)	0.0023 (9)	−0.0134 (11)
C7	0.0289 (13)	0.0286 (13)	0.0308 (13)	−0.0099 (10)	0.0012 (10)	−0.0134 (11)
C8	0.0246 (12)	0.0298 (13)	0.0328 (13)	−0.0064 (10)	−0.0028 (10)	−0.0113 (11)
C9	0.0417 (16)	0.0490 (19)	0.0491 (17)	−0.0189 (14)	0.0113 (14)	−0.0262 (15)
C10	0.059 (2)	0.057 (2)	0.0525 (19)	−0.0261 (17)	0.0132 (16)	−0.0343 (17)
C11	0.062 (2)	0.0420 (18)	0.0505 (19)	−0.0193 (16)	−0.0032 (16)	−0.0225 (15)
C12	0.0514 (18)	0.0367 (16)	0.0500 (18)	−0.0213 (14)	−0.0023 (14)	−0.0101 (14)
C13	0.0357 (14)	0.0327 (15)	0.0364 (14)	−0.0149 (12)	0.0041 (11)	−0.0086 (12)
C14	0.0371 (15)	0.0423 (17)	0.0351 (15)	−0.0154 (13)	−0.0049 (12)	0.0006 (13)
C15	0.0454 (19)	0.045 (2)	0.079 (3)	−0.0088 (16)	−0.0128 (18)	−0.0069 (19)
C16	0.065 (3)	0.062 (3)	0.075 (3)	−0.018 (2)	−0.004 (2)	−0.022 (2)
C17	0.114 (4)	0.067 (3)	0.076 (3)	−0.018 (3)	0.017 (3)	−0.033 (3)
N7	0.114 (4)	0.238 (8)	0.178 (6)	−0.108 (5)	0.087 (4)	−0.161 (6)
C40	0.103 (4)	0.088 (4)	0.066 (3)	−0.056 (3)	0.007 (3)	−0.027 (3)
C41	0.120 (5)	0.121 (5)	0.082 (3)	−0.083 (4)	0.049 (3)	−0.068 (3)

Geometric parameters (Å, º)

Br1—C18	1.896 (3)	C38—H38B	0.9900
F1—C22	1.346 (4)	C39—H39A	0.9800
O6—C29	1.366 (3)	C39—H39B	0.9800
O6—C32	1.412 (5)	C39—H39C	0.9800
O7—C30	1.355 (3)	S1—O1	1.429 (2)
O7—C33	1.438 (3)	S1—O2	1.435 (2)
N3—H3	0.8800	S1—N1	1.591 (3)
N3—C21	1.419 (3)	S1—C1	1.777 (3)
N3—C24	1.355 (4)	O3—C7	1.250 (3)
N4—C24	1.331 (3)	O4—C7	1.271 (3)
N4—C27	1.355 (4)	O5—C6	1.394 (3)
N5—C26	1.385 (4)	O5—C8	1.400 (3)
N5—C27	1.310 (4)	N1—H1A	0.86 (4)
N6—H6	0.85 (4)	N1—H1B	0.79 (5)
N6—C36	1.497 (4)	N2—H2	0.8800
N6—C37	1.490 (4)	N2—C5	1.367 (3)
N6—C39	1.487 (4)	N2—C14	1.448 (4)
C18—C19	1.391 (5)	C1—C2	1.394 (4)
C18—C23	1.370 (5)	C1—C6	1.384 (4)
C19—H19	0.9500	C2—H2A	0.9500
C19—C20	1.380 (4)	C2—C3	1.392 (4)
C20—H20	0.9500	C3—C4	1.392 (4)
C20—C21	1.383 (4)	C3—C7	1.508 (3)
C21—C22	1.390 (4)	C4—H4	0.9500
C22—C23	1.377 (4)	C4—C5	1.403 (4)
C23—H23	0.9500	C5—C6	1.401 (4)
C24—C25	1.434 (4)	C8—C9	1.380 (4)
C25—C26	1.399 (4)	C8—C13	1.373 (4)
C25—C28	1.423 (4)	C9—H9	0.9500
C26—C31	1.416 (4)	C9—C10	1.391 (5)
C27—H27	0.9500	C10—H10	0.9500
C28—H28	0.9500	C10—C11	1.381 (5)
C28—C29	1.368 (4)	C11—H11	0.9500
C29—C30	1.424 (4)	C11—C12	1.380 (5)
C30—C31	1.375 (4)	C12—H12	0.9500
C31—H31	0.9500	C12—C13	1.391 (4)
C32—H32A	0.9800	C13—H13	0.9500
C32—H32B	0.9800	C14—H14A	0.9900
C32—H32C	0.9800	C14—H14B	0.9900
C33—H33A	0.9900	C14—C15	1.542 (6)
C33—H33B	0.9900	C15—H15A	0.9900
C33—C34	1.518 (4)	C15—H15B	0.9900
C34—H34	1.0000	C15—C16	1.492 (6)
C34—C35	1.519 (4)	C16—H16A	0.9900
C34—C38	1.527 (4)	C16—H16B	0.9900
C35—H35A	0.9900	C16—C17	1.502 (7)
C35—H35B	0.9900	C17—H17A	0.9800
C35—C36	1.520 (4)	C17—H17B	0.9800
C36—H36A	0.9900	C17—H17C	0.9800
C36—H36B	0.9900	N7—C41	1.129 (8)
C37—H37A	0.9900	C40—H40A	0.9800
C37—H37B	0.9900	C40—H40B	0.9800
C37—C38	1.516 (4)	C40—H40C	0.9800
C38—H38A	0.9900	C40—C41	1.432 (8)
C29—O6—C32	116.7 (2)	C37—C38—C34	110.1 (2)
C30—O7—C33	118.1 (2)	C37—C38—H38A	109.6
C21—N3—H3	117.4	C37—C38—H38B	109.6
C24—N3—H3	117.4	H38A—C38—H38B	108.1
C24—N3—C21	125.1 (2)	N6—C39—H39A	109.5
C24—N4—C27	116.2 (2)	N6—C39—H39B	109.5
C27—N5—C26	114.7 (2)	N6—C39—H39C	109.5
C36—N6—H6	103 (3)	H39A—C39—H39B	109.5
C37—N6—H6	113 (3)	H39A—C39—H39C	109.5
C37—N6—C36	112.9 (2)	H39B—C39—H39C	109.5
C39—N6—H6	106 (3)	O1—S1—O2	117.84 (15)
C39—N6—C36	109.7 (2)	O1—S1—N1	110.14 (16)
C39—N6—C37	111.6 (2)	O1—S1—C1	106.95 (13)
C19—C18—Br1	119.1 (3)	O2—S1—N1	106.94 (16)
C23—C18—Br1	119.6 (3)	O2—S1—C1	107.57 (13)
C23—C18—C19	121.4 (3)	N1—S1—C1	106.90 (14)
C18—C19—H19	120.8	C6—O5—C8	115.58 (19)
C20—C19—C18	118.4 (3)	S1—N1—H1A	117 (3)
C20—C19—H19	120.8	S1—N1—H1B	115 (4)
C19—C20—H20	119.1	H1A—N1—H1B	126 (4)
C19—C20—C21	121.8 (3)	C5—N2—H2	117.9
C21—C20—H20	119.1	C5—N2—C14	124.1 (2)
C20—C21—N3	120.5 (3)	C14—N2—H2	117.9
C20—C21—C22	117.8 (3)	C2—C1—S1	121.3 (2)
C22—C21—N3	121.3 (3)	C6—C1—S1	118.17 (19)
F1—C22—C21	119.5 (3)	C6—C1—C2	120.5 (2)
F1—C22—C23	118.7 (3)	C1—C2—H2A	120.6
C23—C22—C21	121.7 (3)	C3—C2—C1	118.8 (2)
C18—C23—C22	118.9 (3)	C3—C2—H2A	120.6
C18—C23—H23	120.6	C2—C3—C7	119.2 (2)
C22—C23—H23	120.6	C4—C3—C2	120.5 (2)
N3—C24—C25	119.6 (2)	C4—C3—C7	120.3 (2)
N4—C24—N3	119.1 (2)	C3—C4—H4	119.4
N4—C24—C25	121.3 (3)	C3—C4—C5	121.2 (2)
C26—C25—C24	116.6 (2)	C5—C4—H4	119.4
C26—C25—C28	119.4 (2)	N2—C5—C4	124.0 (2)
C28—C25—C24	124.0 (3)	N2—C5—C6	118.7 (2)
N5—C26—C25	122.0 (2)	C6—C5—C4	117.2 (2)
N5—C26—C31	117.9 (3)	O5—C6—C5	117.9 (2)
C25—C26—C31	120.1 (2)	C1—C6—O5	120.6 (2)
N4—C27—H27	115.4	C1—C6—C5	121.5 (2)
N5—C27—N4	129.3 (3)	O3—C7—O4	123.3 (2)
N5—C27—H27	115.4	O3—C7—C3	118.9 (2)
C25—C28—H28	120.0	O4—C7—C3	117.8 (2)
C29—C28—C25	120.0 (3)	C9—C8—O5	122.5 (2)
C29—C28—H28	120.0	C13—C8—O5	116.6 (2)
O6—C29—C28	124.2 (3)	C13—C8—C9	120.9 (3)
O6—C29—C30	115.2 (2)	C8—C9—H9	120.5
C28—C29—C30	120.6 (2)	C8—C9—C10	119.0 (3)
O7—C30—C29	114.8 (2)	C10—C9—H9	120.5
O7—C30—C31	125.2 (3)	C9—C10—H10	119.6
C31—C30—C29	120.0 (2)	C11—C10—C9	120.7 (3)
C26—C31—H31	120.0	C11—C10—H10	119.6
C30—C31—C26	119.9 (3)	C10—C11—H11	120.2
C30—C31—H31	120.0	C12—C11—C10	119.5 (3)
O6—C32—H32A	109.5	C12—C11—H11	120.2
O6—C32—H32B	109.5	C11—C12—H12	119.9
O6—C32—H32C	109.5	C11—C12—C13	120.2 (3)
H32A—C32—H32B	109.5	C13—C12—H12	119.9
H32A—C32—H32C	109.5	C8—C13—C12	119.8 (3)
H32B—C32—H32C	109.5	C8—C13—H13	120.1
O7—C33—H33A	110.4	C12—C13—H13	120.1
O7—C33—H33B	110.4	N2—C14—H14A	109.4
O7—C33—C34	106.6 (2)	N2—C14—H14B	109.4
H33A—C33—H33B	108.6	N2—C14—C15	111.1 (3)
C34—C33—H33A	110.4	H14A—C14—H14B	108.0
C34—C33—H33B	110.4	C15—C14—H14A	109.4
C33—C34—H34	108.3	C15—C14—H14B	109.4
C33—C34—C35	112.5 (2)	C14—C15—H15A	108.5
C33—C34—C38	111.2 (2)	C14—C15—H15B	108.5
C35—C34—H34	108.3	H15A—C15—H15B	107.5
C35—C34—C38	108.2 (2)	C16—C15—C14	115.2 (3)
C38—C34—H34	108.3	C16—C15—H15A	108.5
C34—C35—H35A	109.5	C16—C15—H15B	108.5
C34—C35—H35B	109.5	C15—C16—H16A	109.4
C34—C35—C36	110.7 (2)	C15—C16—H16B	109.4
H35A—C35—H35B	108.1	C15—C16—C17	111.2 (4)
C36—C35—H35A	109.5	H16A—C16—H16B	108.0
C36—C35—H35B	109.5	C17—C16—H16A	109.4
N6—C36—C35	112.4 (2)	C17—C16—H16B	109.4
N6—C36—H36A	109.1	C16—C17—H17A	109.5
N6—C36—H36B	109.1	C16—C17—H17B	109.5
C35—C36—H36A	109.1	C16—C17—H17C	109.5
C35—C36—H36B	109.1	H17A—C17—H17B	109.5
H36A—C36—H36B	107.9	H17A—C17—H17C	109.5
N6—C37—H37A	109.3	H17B—C17—H17C	109.5
N6—C37—H37B	109.3	H40A—C40—H40B	109.5
N6—C37—C38	111.5 (2)	H40A—C40—H40C	109.5
H37A—C37—H37B	108.0	H40B—C40—H40C	109.5
C38—C37—H37A	109.3	C41—C40—H40A	109.5
C38—C37—H37B	109.3	C41—C40—H40B	109.5
C34—C38—H38A	109.6	C41—C40—H40C	109.5
C34—C38—H38B	109.6	N7—C41—C40	179.0 (6)
Br1—C18—C19—C20	−179.2 (2)	C33—C34—C38—C37	−175.1 (2)
Br1—C18—C23—C22	−179.9 (2)	C34—C35—C36—N6	54.6 (3)
F1—C22—C23—C18	175.7 (3)	C35—C34—C38—C37	60.8 (3)
O6—C29—C30—O7	1.9 (4)	C36—N6—C37—C38	52.4 (3)
O6—C29—C30—C31	−177.0 (3)	C37—N6—C36—C35	−50.8 (3)
O7—C30—C31—C26	−177.6 (2)	C38—C34—C35—C36	−59.1 (3)
O7—C33—C34—C35	−60.8 (3)	C39—N6—C36—C35	−175.9 (2)
O7—C33—C34—C38	177.6 (2)	C39—N6—C37—C38	176.4 (2)
N3—C21—C22—F1	−2.6 (4)	S1—C1—C2—C3	179.1 (2)
N3—C21—C22—C23	174.0 (3)	S1—C1—C6—O5	−1.5 (3)
N3—C24—C25—C26	−178.0 (2)	S1—C1—C6—C5	175.7 (2)
N3—C24—C25—C28	−0.3 (4)	O1—S1—C1—C2	−118.4 (2)
N4—C24—C25—C26	0.2 (4)	O1—S1—C1—C6	61.7 (2)
N4—C24—C25—C28	177.9 (3)	O2—S1—C1—C2	114.1 (2)
N5—C26—C31—C30	176.3 (3)	O2—S1—C1—C6	−65.8 (2)
N6—C37—C38—C34	−57.8 (3)	O5—C8—C9—C10	177.4 (3)
C18—C19—C20—C21	−1.0 (4)	O5—C8—C13—C12	−176.7 (3)
C19—C18—C23—C22	−0.1 (5)	N1—S1—C1—C2	−0.4 (3)
C19—C20—C21—N3	−173.1 (3)	N1—S1—C1—C6	179.6 (2)
C19—C20—C21—C22	0.0 (4)	N2—C5—C6—O5	3.6 (4)
C20—C21—C22—F1	−175.7 (2)	N2—C5—C6—C1	−173.8 (3)
C20—C21—C22—C23	0.9 (4)	N2—C14—C15—C16	61.9 (4)
C21—N3—C24—N4	5.5 (4)	C1—C2—C3—C4	3.3 (4)
C21—N3—C24—C25	−176.2 (2)	C1—C2—C3—C7	−177.8 (2)
C21—C22—C23—C18	−0.9 (4)	C2—C1—C6—O5	178.5 (2)
C23—C18—C19—C20	1.0 (4)	C2—C1—C6—C5	−4.2 (4)
C24—N3—C21—C20	−127.7 (3)	C2—C3—C4—C5	−0.7 (4)
C24—N3—C21—C22	59.4 (4)	C2—C3—C7—O3	7.2 (4)
C24—N4—C27—N5	0.9 (5)	C2—C3—C7—O4	−174.0 (2)
C24—C25—C26—N5	0.5 (4)	C3—C4—C5—N2	176.2 (3)
C24—C25—C26—C31	179.5 (2)	C3—C4—C5—C6	−4.3 (4)
C24—C25—C28—C29	−176.7 (3)	C4—C3—C7—O3	−174.0 (3)
C25—C26—C31—C30	−2.7 (4)	C4—C3—C7—O4	4.8 (4)
C25—C28—C29—O6	175.8 (3)	C4—C5—C6—O5	−176.0 (2)
C25—C28—C29—C30	−2.5 (4)	C4—C5—C6—C1	6.7 (4)
C26—N5—C27—N4	−0.2 (5)	C5—N2—C14—C15	77.1 (4)
C26—C25—C28—C29	0.9 (4)	C6—O5—C8—C9	29.6 (4)
C27—N4—C24—N3	177.4 (2)	C6—O5—C8—C13	−153.5 (2)
C27—N4—C24—C25	−0.8 (4)	C6—C1—C2—C3	−0.9 (4)
C27—N5—C26—C25	−0.5 (4)	C7—C3—C4—C5	−179.5 (2)
C27—N5—C26—C31	−179.5 (3)	C8—O5—C6—C1	−106.0 (3)
C28—C25—C26—N5	−177.3 (2)	C8—O5—C6—C5	76.6 (3)
C28—C25—C26—C31	1.7 (4)	C8—C9—C10—C11	−1.1 (6)
C28—C29—C30—O7	−179.6 (2)	C9—C8—C13—C12	0.4 (5)
C28—C29—C30—C31	1.5 (4)	C9—C10—C11—C12	0.8 (6)
C29—C30—C31—C26	1.1 (4)	C10—C11—C12—C13	0.1 (5)
C30—O7—C33—C34	176.8 (2)	C11—C12—C13—C8	−0.7 (5)
C32—O6—C29—C28	−22.9 (5)	C13—C8—C9—C10	0.5 (5)
C32—O6—C29—C30	155.5 (3)	C14—N2—C5—C4	6.0 (5)
C33—O7—C30—C29	−168.9 (2)	C14—N2—C5—C6	−173.5 (3)
C33—O7—C30—C31	9.9 (4)	C14—C15—C16—C17	−178.8 (4)
C33—C34—C35—C36	177.6 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O3^i	0.86 (4)	2.02 (5)	2.830 (4)	158 (4)
N1—H1B···N7^i	0.79 (5)	2.37 (5)	3.046 (8)	144 (5)
N3—H3···O4^ii	0.88	2..01	2.818 (3)	153
N6—H6···O3^iii	0.85 (5)	2.34 (5)	3.050 (3)	142 (4)
N6—H6···O4^iii	0.85 (5)	1.97 (5)	2.734 (3)	149 (5)

Symmetry codes: (i) −x+1, −y+1, −z+2; (ii) −x+1, −y+2, −z+1; (iii) −x+1, −y+1, −z+1.