Understanding the structure details when drying hydrate crystals of pharmaceuticals - interpretations from diffuse scattering and inter-modulation satellites of a partially dehydrated crystal

Simplified models for the crystal lattice of the sesquihydrate form of the hemi-sulfate salt of (5S,6S,9R)-5-amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl 4-(2-oxo-2,3-dihydro-1H-imidazol[4,5b]pyridin-1-yl)-1-piperidine carboxylate (BMS-927711, C₂₈H₂₉F₂N₆O₃⁺) are used to calculate diffuse diffraction features in order to develop a mechanistic understanding of the dehydration process with respect to disruption of the lattice, since a Bragg model cannot be established. The model demonstrates that what we observe when the water leaves the crystal is partial transformation from the parent form to a child form (a new form, less hydrated and structurally related to the parent). Yet this `dried' structure is not a pure phase. It consists of semi-random layers of both child, parent and an interfacial layer which has a modulated structure that represents a transitory phase. Understanding the fact that a single `dried' crystal can have the disordered layer structure described as well as understanding mechanistic relationships between the phases involved can have implications in understanding the effect of common large scale bulk drying procedures. During the development of BMS-927711, difficulties did arise during characterization of the dried bulk when using only routine solid-state analysis. The material is now better understood from this diffraction study. The diffraction experiments also reveal intermodulation satellites, which upon interpretation yield even more structural information about the crystal transformation. The model suggests the mechanism of transformation is laminar in which layers of the crystal are driven to approach a stable B-centered supercell phase of lower water content.

Computing details

Data collection: Bruker APEX2; cell refinement: Bruker SAINT; data reduction: Bruker SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: Bruker SHELXTL; software used to prepare material for publication: Bruker SHELXTL.

BMS-927711–0.5H2SO4 H1.5–1 sesquihydrate CGRP

Crystal data

C28H29F2N6O3^+·0.5(O4S^2^−)·1.5(H2O)	F(000) = 1280
Mr = 610.63	Dx = 1.423 Mg m^−3
Orthorhombic, P21212	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: P_2_2ab	Cell parameters from 7294 reflections
a = 10.9169 (9) Å	θ = 2.7–54.0°
b = 33.039 (3) Å	µ = 1.27 mm^−1
c = 7.9038 (6) Å	T = 296 K
V = 2850.8 (4) Å^3	Prism, colorless
Z = 4	0.26 × 0.22 × 0.18 mm

Data collection

Bruker APEX-II CCD diffractometer	3509 independent reflections
Radiation source: fine-focus sealed tube	3235 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.035
φ and ω scans	θmax = 55.1°, θmin = 2.7°
Absorption correction: multi-scan SADABS (Sheldrick, 1996)	h = −11→11
Tmin = 0.755, Tmax = 0.796	k = −35→34
18471 measured reflections	l = −8→8

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.038	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.100	w = 1/[σ^2(Fo^2) + (0.056P)^2 + 1.0338P] where P = (Fo^2 + 2Fc^2)/3
S = 1.04	(Δ/σ)max < 0.001
3509 reflections	Δρmax = 0.39 e Å^−3
399 parameters	Δρmin = −0.18 e Å^−3
5 restraints	Absolute structure: Flack H D (1983), Acta Cryst. A39, 876-881
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.01 (3)

Special details

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.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
C1	0.7702 (3)	0.86785 (9)	0.5047 (4)	0.0448 (8)
C2	0.7665 (3)	0.83757 (9)	0.6299 (4)	0.0433 (8)
C3	0.9272 (3)	0.87905 (9)	0.6797 (4)	0.0435 (8)
C4	0.6025 (4)	0.84318 (13)	0.3770 (5)	0.0699 (11)
H4	0.5448	0.8444	0.2906	0.084*
C5	0.5920 (4)	0.81282 (13)	0.4927 (5)	0.0684 (11)
H5	0.5274	0.7946	0.4840	0.082*
C6	0.6764 (3)	0.80866 (11)	0.6238 (5)	0.0577 (9)
H6	0.6720	0.7877	0.7021	0.069*
C7	0.9084 (3)	0.82233 (9)	0.8839 (4)	0.0456 (8)
H7	0.9727	0.8389	0.9355	0.055*
C8	0.9695 (3)	0.78267 (10)	0.8327 (5)	0.0537 (9)
H8A	0.9099	0.7650	0.7791	0.064*
H8B	1.0345	0.7880	0.7520	0.064*
C9	1.0218 (3)	0.76215 (11)	0.9881 (5)	0.0632 (10)
H9A	1.0543	0.7359	0.9569	0.076*
H9B	1.0887	0.7783	1.0327	0.076*
C10	0.8686 (4)	0.79452 (10)	1.1700 (4)	0.0581 (9)
H10A	0.9281	0.8121	1.2238	0.070*
H10B	0.8047	0.7886	1.2517	0.070*
C11	0.8134 (3)	0.81586 (10)	1.0190 (4)	0.0527 (9)
H11A	0.7467	0.7998	0.9738	0.063*
H11B	0.7803	0.8418	1.0541	0.063*
C12	0.8697 (3)	0.72181 (9)	1.1470 (4)	0.0446 (8)
C13	0.7480 (3)	0.68155 (12)	0.6484 (5)	0.0633 (10)
H13	0.7567	0.7029	0.5727	0.076*
C14	0.6737 (4)	0.64982 (12)	0.6034 (5)	0.0665 (10)
H14	0.6353	0.6493	0.4984	0.080*
C15	0.6572 (3)	0.61860 (11)	0.7183 (5)	0.0560 (9)
H15	0.6064	0.5969	0.6916	0.067*
C16	0.7163 (3)	0.61982 (9)	0.8726 (4)	0.0450 (8)
C17	0.7940 (3)	0.65271 (9)	0.9039 (4)	0.0465 (8)
C18	0.7080 (3)	0.58701 (9)	1.0058 (4)	0.0466 (8)
H18	0.7040	0.6002	1.1167	0.056*
C19	0.8201 (3)	0.55907 (9)	1.0055 (4)	0.0482 (8)
H19	0.8075	0.5406	0.9102	0.058*
C20	0.9403 (3)	0.58149 (10)	0.9660 (5)	0.0539 (9)
H20A	1.0071	0.5626	0.9831	0.065*
H20B	0.9395	0.5884	0.8467	0.065*
C21	0.9708 (3)	0.62003 (10)	1.0646 (5)	0.0544 (9)
H21A	1.0450	0.6316	1.0175	0.065*
H21B	0.9882	0.6126	1.1809	0.065*
C22	0.8709 (3)	0.65265 (9)	1.0646 (4)	0.0467 (8)
H22	0.8173	0.6486	1.1626	0.056*
C23	0.8230 (3)	0.53227 (10)	1.1619 (4)	0.0488 (8)
C24	0.8222 (3)	0.49037 (11)	1.1444 (5)	0.0642 (10)
H24	0.8191	0.4792	1.0344	0.077*
C25	0.8278 (3)	0.46539 (15)	1.2797 (7)	0.0846 (14)
H25	0.8243	0.4381	1.2622	0.101*
C26	0.8326 (4)	0.47904 (17)	1.4381 (7)	0.0884 (14)
H26	0.8303	0.4613	1.5296	0.106*
C27	0.8409 (4)	0.51975 (18)	1.4617 (6)	0.0867 (14)
C28	0.8331 (4)	0.54614 (13)	1.3244 (5)	0.0716 (12)
N1	0.8644 (2)	0.84509 (7)	0.7370 (3)	0.0446 (6)
N2	0.8677 (2)	0.89196 (7)	0.5375 (3)	0.0476 (7)
H2	0.8891	0.9125	0.4774	0.057*
N3	0.6912 (3)	0.87166 (9)	0.3793 (4)	0.0600 (8)
N4	0.9279 (3)	0.75706 (8)	1.1190 (4)	0.0532 (7)
N5	0.8091 (3)	0.68348 (8)	0.7965 (4)	0.0543 (7)
N6	0.5959 (2)	0.56172 (8)	0.9862 (4)	0.0534 (7)
H6A	0.6054	0.5449	0.8992	0.080*
H6B	0.5316	0.5777	0.9675	0.080*
H6C	0.5836	0.5475	1.0803	0.080*
O1	1.0190 (2)	0.89331 (7)	0.7438 (3)	0.0618 (6)
O2	0.7746 (2)	0.71789 (7)	1.2241 (3)	0.0616 (6)
O3	0.9356 (2)	0.69038 (6)	1.0833 (3)	0.0509 (6)
O4	0.3908 (2)	0.49846 (8)	0.7592 (3)	0.0659 (7)
O5	0.4930 (3)	0.53644 (7)	0.5467 (3)	0.0749 (8)
S1	0.5000	0.5000	0.64941 (14)	0.0455 (3)
O1S	0.5000	0.5000	0.2134 (5)	0.0820 (11)
H1SA	0.4864	0.5219	0.2659	0.123*
O2S	0.3401 (3)	0.57842 (8)	0.8737 (4)	0.0800 (8)
H2SA	0.3380	0.5533	0.8525	0.120*
H2SB	0.2905	0.5909	0.8107	0.120*
F1	0.8437 (3)	0.58440 (8)	1.3581 (3)	0.0868 (11)	0.817 (5)
F2	0.8604 (4)	0.53426 (12)	1.6124 (4)	0.1079 (13)	0.817 (5)
F1A	0.8206 (8)	0.4781 (5)	0.9853 (10)	0.114 (6)*	0.183 (5)
F2A	0.8316 (9)	0.4256 (2)	1.266 (3)	0.159 (8)*	0.183 (5)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.045 (2)	0.0464 (18)	0.0433 (19)	0.0033 (15)	0.0001 (18)	−0.0055 (15)
C2	0.0402 (19)	0.0449 (17)	0.0449 (18)	−0.0008 (15)	−0.0003 (17)	−0.0031 (16)
C3	0.046 (2)	0.0419 (18)	0.042 (2)	−0.0034 (16)	−0.0003 (17)	−0.0005 (15)
C4	0.054 (2)	0.093 (3)	0.063 (3)	−0.010 (2)	−0.020 (2)	0.004 (2)
C5	0.052 (2)	0.083 (3)	0.070 (3)	−0.024 (2)	−0.008 (2)	−0.003 (2)
C6	0.056 (2)	0.064 (2)	0.053 (2)	−0.0154 (18)	−0.005 (2)	0.0046 (17)
C7	0.0461 (19)	0.0446 (17)	0.046 (2)	−0.0073 (14)	−0.0118 (17)	0.0078 (15)
C8	0.050 (2)	0.054 (2)	0.057 (2)	−0.0021 (16)	0.0121 (18)	0.0117 (17)
C9	0.048 (2)	0.057 (2)	0.084 (3)	−0.0025 (17)	0.005 (2)	0.020 (2)
C10	0.075 (2)	0.0475 (19)	0.052 (2)	−0.0057 (19)	−0.004 (2)	0.0002 (16)
C11	0.064 (2)	0.0449 (18)	0.049 (2)	0.0024 (16)	0.0021 (19)	−0.0034 (15)
C12	0.046 (2)	0.051 (2)	0.0369 (18)	−0.0023 (17)	−0.0115 (18)	0.0056 (16)
C13	0.060 (2)	0.067 (2)	0.062 (3)	0.0022 (19)	0.001 (2)	0.010 (2)
C14	0.063 (2)	0.076 (3)	0.060 (2)	0.003 (2)	−0.013 (2)	0.001 (2)
C15	0.049 (2)	0.058 (2)	0.061 (2)	−0.0013 (17)	−0.0095 (19)	−0.0097 (19)
C16	0.0386 (17)	0.0463 (17)	0.050 (2)	0.0023 (15)	0.0017 (17)	−0.0073 (16)
C17	0.0385 (18)	0.0491 (19)	0.052 (2)	−0.0004 (15)	0.0042 (17)	−0.0041 (16)
C18	0.0412 (18)	0.0478 (17)	0.051 (2)	−0.0102 (15)	0.0080 (17)	−0.0130 (15)
C19	0.051 (2)	0.0475 (18)	0.0460 (19)	0.0009 (15)	0.0094 (17)	−0.0116 (15)
C20	0.0462 (19)	0.057 (2)	0.059 (2)	0.0048 (16)	0.0067 (18)	0.0009 (18)
C21	0.0451 (19)	0.0560 (19)	0.062 (2)	−0.0024 (16)	0.0018 (17)	0.0081 (17)
C22	0.0437 (18)	0.0449 (18)	0.052 (2)	−0.0085 (15)	−0.0006 (17)	−0.0011 (15)
C23	0.0395 (18)	0.058 (2)	0.049 (2)	−0.0014 (15)	0.0070 (17)	−0.0001 (17)
C24	0.060 (2)	0.064 (2)	0.068 (2)	0.0067 (18)	0.006 (2)	0.018 (2)
C25	0.079 (3)	0.081 (3)	0.094 (4)	0.014 (2)	0.035 (3)	0.014 (3)
C26	0.079 (3)	0.098 (4)	0.089 (4)	−0.002 (3)	0.014 (3)	0.031 (3)
C27	0.084 (3)	0.133 (4)	0.044 (3)	−0.037 (3)	0.004 (2)	−0.002 (3)
C28	0.085 (3)	0.081 (3)	0.049 (2)	−0.028 (2)	0.014 (2)	−0.009 (2)
N1	0.0444 (15)	0.0418 (14)	0.0474 (16)	−0.0098 (12)	−0.0088 (15)	0.0067 (12)
N2	0.0526 (16)	0.0432 (14)	0.0469 (16)	−0.0066 (13)	−0.0029 (15)	0.0051 (12)
N3	0.0532 (18)	0.074 (2)	0.0528 (18)	−0.0002 (16)	−0.0116 (17)	0.0042 (15)
N4	0.0537 (16)	0.0484 (16)	0.0575 (18)	−0.0059 (13)	−0.0013 (16)	0.0124 (14)
N5	0.0511 (17)	0.0587 (17)	0.0532 (18)	−0.0016 (14)	−0.0042 (15)	0.0046 (14)
N6	0.0520 (17)	0.0488 (15)	0.0594 (18)	−0.0053 (13)	0.0091 (15)	−0.0119 (14)
O1	0.0610 (16)	0.0610 (14)	0.0633 (15)	−0.0266 (12)	−0.0119 (15)	0.0071 (12)
O2	0.0555 (15)	0.0637 (15)	0.0657 (16)	−0.0076 (12)	0.0118 (14)	0.0056 (13)
O3	0.0451 (12)	0.0477 (12)	0.0600 (15)	−0.0097 (11)	−0.0033 (11)	0.0008 (11)
O4	0.0544 (14)	0.0680 (15)	0.0752 (16)	0.0066 (12)	0.0120 (13)	0.0230 (15)
O5	0.102 (2)	0.0499 (13)	0.0729 (17)	0.0152 (14)	0.0111 (18)	0.0209 (12)
S1	0.0573 (7)	0.0355 (6)	0.0436 (6)	−0.0002 (5)	0.000	0.000
O1S	0.106 (3)	0.079 (2)	0.061 (2)	−0.004 (2)	0.000	0.000
O2S	0.0904 (19)	0.0647 (15)	0.0848 (19)	0.0085 (14)	−0.0066 (17)	0.0017 (14)
F1	0.129 (3)	0.0764 (19)	0.0553 (16)	−0.0257 (17)	0.0149 (18)	−0.0219 (14)
F2	0.131 (3)	0.145 (3)	0.0477 (18)	−0.045 (2)	0.0083 (19)	−0.0040 (18)

Geometric parameters (Å, º)

C1—N3	1.320 (4)	C16—C18	1.514 (5)
C1—N2	1.355 (4)	C17—N5	1.335 (4)
C1—C2	1.408 (5)	C17—C22	1.523 (5)
C2—C6	1.372 (5)	C18—N6	1.491 (4)
C2—N1	1.386 (4)	C18—C19	1.533 (5)
C3—O1	1.217 (4)	C18—H18	0.9800
C3—N2	1.366 (4)	C19—C23	1.521 (5)
C3—N1	1.391 (4)	C19—C20	1.539 (5)
C4—N3	1.350 (5)	C19—H19	0.9800
C4—C5	1.362 (6)	C20—C21	1.530 (5)
C4—H4	0.9300	C20—H20A	0.9700
C5—C6	1.394 (5)	C20—H20B	0.9700
C5—H5	0.9300	C21—C22	1.533 (4)
C6—H6	0.9300	C21—H21A	0.9700
C7—N1	1.464 (4)	C21—H21B	0.9700
C7—C11	1.504 (5)	C22—O3	1.440 (4)
C7—C8	1.525 (5)	C22—H22	0.9800
C7—H7	0.9800	C23—C28	1.368 (5)
C8—C9	1.515 (5)	C23—C24	1.391 (5)
C8—H8A	0.9700	C24—C25	1.352 (6)
C8—H8B	0.9700	C24—H24	0.9451
C9—N4	1.466 (5)	C25—C26	1.332 (7)
C9—H9A	0.9700	C25—H25	0.9133
C9—H9B	0.9700	C26—C27	1.361 (7)
C10—N4	1.454 (4)	C26—H26	0.9300
C10—C11	1.511 (5)	C27—F2	1.302 (5)
C10—H10A	0.9700	C27—C28	1.395 (6)
C10—H10B	0.9700	C28—F1	1.297 (5)
C11—H11A	0.9700	N2—H2	0.8600
C11—H11B	0.9700	N6—H6A	0.8900
C12—O2	1.211 (4)	N6—H6B	0.8900
C12—N4	1.345 (4)	N6—H6C	0.8900
C12—O3	1.360 (4)	O4—S1	1.476 (2)
C13—N5	1.349 (5)	O5—S1	1.454 (2)
C13—C14	1.372 (5)	S1—O5^i	1.454 (2)
C13—H13	0.9300	S1—O4^i	1.476 (2)
C14—C15	1.386 (5)	O1S—H1SA	0.8461
C14—H14	0.9300	O2S—H2SA	0.8481
C15—C16	1.380 (5)	O2S—H2SB	0.8439
C15—H15	0.9300	F1A—H24	0.3905
C16—C17	1.401 (4)	F2A—H25	0.4225
N3—C1—N2	127.0 (3)	C16—C18—H18	107.8
N3—C1—C2	125.2 (3)	C19—C18—H18	107.8
N2—C1—C2	107.8 (3)	C23—C19—C18	111.5 (3)
C6—C2—N1	134.4 (3)	C23—C19—C20	115.3 (3)
C6—C2—C1	119.4 (3)	C18—C19—C20	113.0 (3)
N1—C2—C1	106.2 (3)	C23—C19—H19	105.3
O1—C3—N2	127.8 (3)	C18—C19—H19	105.3
O1—C3—N1	125.6 (3)	C20—C19—H19	105.3
N2—C3—N1	106.6 (3)	C21—C20—C19	118.9 (3)
N3—C4—C5	124.4 (4)	C21—C20—H20A	107.6
N3—C4—H4	117.8	C19—C20—H20A	107.6
C5—C4—H4	117.8	C21—C20—H20B	107.6
C4—C5—C6	121.1 (3)	C19—C20—H20B	107.6
C4—C5—H5	119.5	H20A—C20—H20B	107.0
C6—C5—H5	119.5	C20—C21—C22	115.5 (3)
C2—C6—C5	115.6 (3)	C20—C21—H21A	108.4
C2—C6—H6	122.2	C22—C21—H21A	108.4
C5—C6—H6	122.2	C20—C21—H21B	108.4
N1—C7—C11	114.2 (3)	C22—C21—H21B	108.4
N1—C7—C8	112.0 (3)	H21A—C21—H21B	107.5
C11—C7—C8	111.6 (3)	O3—C22—C17	110.8 (3)
N1—C7—H7	106.1	O3—C22—C21	105.0 (2)
C11—C7—H7	106.1	C17—C22—C21	113.1 (3)
C8—C7—H7	106.1	O3—C22—H22	109.3
C9—C8—C7	109.5 (3)	C17—C22—H22	109.3
C9—C8—H8A	109.8	C21—C22—H22	109.3
C7—C8—H8A	109.8	C28—C23—C24	115.3 (4)
C9—C8—H8B	109.8	C28—C23—C19	124.7 (3)
C7—C8—H8B	109.8	C24—C23—C19	119.9 (3)
H8A—C8—H8B	108.2	C25—C24—C23	121.9 (4)
N4—C9—C8	111.1 (3)	C25—C24—H24	119.4
N4—C9—H9A	109.4	C23—C24—H24	118.7
C8—C9—H9A	109.4	C26—C25—C24	122.6 (5)
N4—C9—H9B	109.4	C26—C25—H25	118.6
C8—C9—H9B	109.4	C24—C25—H25	118.8
H9A—C9—H9B	108.0	C25—C26—C27	117.8 (5)
N4—C10—C11	110.8 (3)	C25—C26—H26	121.1
N4—C10—H10A	109.5	C27—C26—H26	121.1
C11—C10—H10A	109.5	F2—C27—C26	120.0 (5)
N4—C10—H10B	109.5	F2—C27—C28	119.5 (5)
C11—C10—H10B	109.5	C26—C27—C28	120.5 (5)
H10A—C10—H10B	108.1	F1—C28—C23	121.8 (4)
C7—C11—C10	110.6 (3)	F1—C28—C27	116.3 (4)
C7—C11—H11A	109.5	C23—C28—C27	121.7 (4)
C10—C11—H11A	109.5	C2—N1—C3	109.0 (3)
C7—C11—H11B	109.5	C2—N1—C7	130.2 (2)
C10—C11—H11B	109.5	C3—N1—C7	120.7 (3)
H11A—C11—H11B	108.1	C1—N2—C3	110.3 (3)
O2—C12—N4	125.5 (3)	C1—N2—H2	124.8
O2—C12—O3	124.0 (3)	C3—N2—H2	124.8
N4—C12—O3	110.5 (3)	C1—N3—C4	114.3 (3)
N5—C13—C14	123.6 (4)	C12—N4—C10	118.7 (3)
N5—C13—H13	118.2	C12—N4—C9	123.1 (3)
C14—C13—H13	118.2	C10—N4—C9	114.2 (3)
C13—C14—C15	118.4 (4)	C17—N5—C13	117.1 (3)
C13—C14—H14	120.8	C18—N6—H6A	109.5
C15—C14—H14	120.8	C18—N6—H6B	109.5
C16—C15—C14	119.7 (3)	H6A—N6—H6B	109.5
C16—C15—H15	120.1	C18—N6—H6C	109.5
C14—C15—H15	120.1	H6A—N6—H6C	109.5
C15—C16—C17	117.5 (3)	H6B—N6—H6C	109.5
C15—C16—C18	124.5 (3)	C12—O3—C22	116.0 (2)
C17—C16—C18	117.9 (3)	O5—S1—O5^i	112.1 (2)
N5—C17—C16	123.6 (3)	O5—S1—O4^i	110.02 (16)
N5—C17—C22	117.6 (3)	O5^i—S1—O4^i	108.34 (15)
C16—C17—C22	118.7 (3)	O5—S1—O4	108.34 (15)
N6—C18—C16	112.2 (3)	O5^i—S1—O4	110.02 (16)
N6—C18—C19	108.5 (2)	O4^i—S1—O4	107.9 (2)
C16—C18—C19	112.5 (3)	H2SA—O2S—H2SB	110.2
N6—C18—H18	107.8

Symmetry code: (i) −x+1, −y+1, z.