The preparation, characterization, structure and dissolution analysis of apremilast solvatomorphs

Apremilast (AP) {systematic name: (S)-2-[1-(3-eth­oxy-4-meth­oxy­phen­yl)-2-(methyl­sulfon­yl)eth­yl]-4-acetamido­isoindoline-1,3-dione} is an inhibitor of phospho­dieasterase-4 (PDE4) and is indicated for the treatment of adult patients with active psoriatic arthritis. The ability of AP to form solvates has been investigated and three solvatomorphs of AP, namely, the AP ethyl acetate hemisolvate, C₂₂H₂₄N₂O₇S·0.5C₄H₈O₂, the AP toluene hemisolvate, C₂₂H₂₄N₂O₇S·0.5C₇H₈, and the AP di­chloro­methane monosolvate, C₂₂H₂₄N₂O₇S·CH₂Cl₂, were obtained. The three AP solvatomorphs were characterized by X-ray powder diffraction, thermogravimetric analysis and differential scanning calorimetry. Single-crystal X-ray diffraction was used to analyze the structures, crystal symmetry, packing modes, stoichiometry and hydrogen-bonding inter­actions of the solvatomorphs. In addition, dissolution analyses were performed to study the dissolution rates of different AP solvatomorph tablets in vitro and to make comparisons with commercial apremilast tablets (produced by Celgene); all three solvatomorphs showed similar dissolution rates and similar values of the similarity factor f₂ in a comparison of their dissolution profiles.

Computing details

For all compounds, data collection: CAD-4 EXPRESS (Enraf–Nonius, 1989); cell refinement: CAD-4 EXPRESS (Enraf–Nonius, 1989); data reduction: XCAD4 (Harms & Wocadlo, 1995); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009) and PLATON (Spek, 2009).

(1) (S)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-4-acetamidoisoindoline-1,3-dione ethyl acetate hemisolvate

Crystal data

C22H24N2O7S·0.5C4H8O2	Dx = 1.327 Mg m^−3
Mr = 504.54	Mo Kα radiation, λ = 0.71073 Å
Tetragonal, P41212	Cell parameters from 25 reflections
a = 13.0307 (18) Å	θ = 9–12°
c = 29.754 (6) Å	µ = 0.18 mm^−1
V = 5052.2 (17) Å^3	T = 293 K
Z = 8	Block, colourless
F(000) = 2128	0.3 × 0.2 × 0.1 mm

Data collection

Enraf–Nonius CAD-4 diffractometer	θmax = 25.4°, θmin = 1.7°
ω/2θ scans	h = −15→15
7571 measured reflections	k = −15→0
4617 independent reflections	l = −35→0
2777 reflections with I > 2σ(I)	1 standard reflections every 60 reflections
Rint = 0.061	intensity decay: 1%

Refinement

Refinement on F^2	Hydrogen site location: mixed
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.058	w = 1/[σ^2(Fo^2) + (0.067P)^2] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.143	(Δ/σ)max = 0.001
S = 0.96	Δρmax = 0.17 e Å^−3
4617 reflections	Δρmin = −0.22 e Å^−3
345 parameters	Absolute structure: Flack x determined using 807 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
32 restraints	Absolute structure parameter: −0.03 (10)

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	Occ. (<1)
S1	0.84057 (12)	0.60020 (12)	0.53731 (5)	0.0522 (4)
O1	0.9254 (3)	0.5579 (3)	0.56191 (16)	0.0721 (13)
O2	0.7935 (3)	0.6922 (3)	0.55414 (14)	0.0679 (12)
O3	0.4666 (3)	0.2486 (3)	0.48318 (14)	0.0641 (12)
O4	0.4491 (3)	0.1140 (3)	0.54722 (15)	0.0705 (13)
O5	0.5361 (3)	0.6031 (3)	0.55366 (13)	0.0593 (11)
O6	0.7587 (3)	0.5242 (3)	0.66688 (13)	0.0544 (10)
O7	0.6748 (4)	0.8016 (3)	0.78838 (15)	0.0742 (13)
N1	0.6583 (3)	0.5423 (3)	0.60341 (14)	0.0415 (10)
N2	0.7012 (4)	0.6828 (4)	0.73425 (15)	0.0529 (13)
H2	0.7386	0.6305	0.7276	0.063*
C1	0.7060 (4)	0.4613 (4)	0.57588 (18)	0.0423 (13)
H1	0.7658	0.4360	0.5925	0.051*
C2	0.7453 (4)	0.5045 (4)	0.53158 (18)	0.0433 (12)
H2A	0.6878	0.5331	0.5151	0.052*
H2B	0.7732	0.4486	0.5138	0.052*
C3	0.8786 (6)	0.6213 (6)	0.4821 (2)	0.077 (2)
H3A	0.9283	0.6756	0.4813	0.116*
H3B	0.8200	0.6402	0.4644	0.116*
H3C	0.9084	0.5597	0.4702	0.116*
C4	0.6348 (4)	0.3698 (4)	0.56847 (18)	0.0427 (13)
C5	0.6225 (4)	0.3000 (4)	0.6021 (2)	0.0522 (15)
H5	0.6556	0.3103	0.6294	0.063*
C6	0.5610 (5)	0.2130 (4)	0.5963 (2)	0.0551 (16)
H6	0.5545	0.1655	0.6194	0.066*
C7	0.5103 (5)	0.1976 (4)	0.5565 (2)	0.0517 (15)
C8	0.5205 (4)	0.2690 (4)	0.5218 (2)	0.0510 (14)
C9	0.5818 (4)	0.3541 (4)	0.5282 (2)	0.0515 (15)
H9	0.5879	0.4021	0.5052	0.062*
C10	0.4688 (5)	0.3237 (5)	0.4481 (2)	0.0682 (19)
H10A	0.5383	0.3317	0.4371	0.082*
H10B	0.4457	0.3894	0.4596	0.082*
C11	0.4004 (7)	0.2898 (6)	0.4110 (3)	0.105 (3)
H11A	0.4035	0.3387	0.3868	0.158*
H11B	0.3311	0.2850	0.4218	0.158*
H11C	0.4224	0.2239	0.4003	0.158*
C12	0.4314 (7)	0.0455 (5)	0.5843 (3)	0.094 (3)
H12A	0.3892	−0.0107	0.5746	0.141*
H12B	0.3972	0.0818	0.6080	0.141*
H12C	0.4958	0.0196	0.5951	0.141*
C13	0.5795 (4)	0.6082 (4)	0.5895 (2)	0.0465 (14)
C14	0.5633 (4)	0.6827 (4)	0.62655 (19)	0.0458 (13)
C15	0.4952 (5)	0.7644 (4)	0.6297 (2)	0.0596 (16)
H15	0.4500	0.7810	0.6066	0.072*
C16	0.4988 (5)	0.8195 (5)	0.6693 (2)	0.0572 (16)
H16	0.4544	0.8748	0.6726	0.069*
C17	0.5642 (4)	0.7971 (4)	0.7039 (2)	0.0545 (15)
H17	0.5631	0.8369	0.7298	0.065*
C18	0.6331 (4)	0.7144 (4)	0.70054 (19)	0.0447 (13)
C19	0.6307 (4)	0.6579 (4)	0.66090 (18)	0.0413 (13)
C20	0.6915 (4)	0.5690 (4)	0.64645 (18)	0.0413 (12)
C21	0.7160 (5)	0.7227 (5)	0.7755 (2)	0.0548 (15)
C22	0.7870 (6)	0.6629 (6)	0.8051 (2)	0.077 (2)
H22A	0.8015	0.7018	0.8318	0.115*
H22B	0.8498	0.6494	0.7893	0.115*
H22C	0.7552	0.5991	0.8133	0.115*
O15	0.5512 (8)	0.4488 (8)	0.2500	0.157 (4)
C45	0.433 (4)	0.593 (5)	0.245 (3)	0.199 (14)	0.5
H45A	0.4890	0.6292	0.2320	0.298*	0.5
H45B	0.3981	0.6368	0.2663	0.298*	0.5
H45C	0.3855	0.5721	0.2222	0.298*	0.5
O16	0.464 (3)	0.462 (3)	0.3131 (11)	0.314 (15)	0.5
C46	0.473 (3)	0.497 (3)	0.2700 (13)	0.187 (10)	0.5
C47	0.596 (2)	0.371 (2)	0.2723 (10)	0.172 (9)	0.5
H47A	0.5479	0.3145	0.2769	0.207*	0.5
H47B	0.6225	0.3929	0.3011	0.207*	0.5
C48	0.683 (5)	0.340 (5)	0.239 (2)	0.247 (16)	0.5
H48A	0.7057	0.2717	0.2459	0.371*	0.5
H48B	0.7398	0.3868	0.2429	0.371*	0.5
H48C	0.6584	0.3434	0.2090	0.371*	0.5

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0539 (9)	0.0522 (9)	0.0503 (9)	−0.0110 (7)	0.0039 (8)	−0.0052 (8)
O1	0.054 (2)	0.075 (3)	0.087 (3)	−0.008 (2)	−0.021 (2)	0.001 (3)
O2	0.083 (3)	0.052 (2)	0.069 (3)	−0.003 (2)	0.008 (2)	−0.011 (2)
O3	0.081 (3)	0.055 (2)	0.056 (3)	−0.021 (2)	−0.023 (2)	0.008 (2)
O4	0.080 (3)	0.051 (2)	0.080 (3)	−0.022 (2)	−0.001 (2)	0.008 (2)
O5	0.059 (2)	0.073 (3)	0.046 (2)	0.001 (2)	−0.015 (2)	0.007 (2)
O6	0.062 (3)	0.056 (3)	0.046 (2)	0.0124 (19)	−0.013 (2)	0.0011 (19)
O7	0.094 (3)	0.071 (3)	0.058 (3)	0.010 (3)	0.003 (2)	−0.020 (2)
N1	0.042 (2)	0.045 (2)	0.039 (3)	0.003 (2)	−0.006 (2)	0.001 (2)
N2	0.064 (3)	0.053 (3)	0.042 (3)	0.012 (3)	−0.009 (2)	−0.007 (2)
C1	0.043 (3)	0.051 (3)	0.033 (3)	−0.002 (3)	−0.003 (3)	0.002 (3)
C2	0.045 (3)	0.047 (3)	0.037 (3)	−0.005 (2)	0.000 (3)	−0.005 (3)
C3	0.089 (5)	0.087 (5)	0.055 (4)	−0.020 (4)	0.020 (4)	0.006 (4)
C4	0.046 (3)	0.047 (3)	0.036 (3)	−0.001 (3)	−0.002 (3)	0.003 (3)
C5	0.062 (4)	0.054 (4)	0.041 (3)	−0.001 (3)	−0.001 (3)	0.007 (3)
C6	0.068 (4)	0.044 (3)	0.053 (4)	−0.008 (3)	0.004 (3)	0.012 (3)
C7	0.060 (4)	0.042 (3)	0.054 (4)	−0.008 (3)	0.004 (3)	0.005 (3)
C8	0.056 (4)	0.044 (3)	0.054 (4)	−0.004 (3)	−0.005 (3)	−0.002 (3)
C9	0.056 (4)	0.041 (3)	0.058 (4)	−0.005 (3)	0.000 (3)	0.009 (3)
C10	0.086 (5)	0.054 (4)	0.064 (4)	−0.006 (4)	−0.020 (4)	0.002 (3)
C11	0.141 (8)	0.096 (6)	0.080 (6)	−0.020 (6)	−0.048 (6)	0.010 (5)
C12	0.140 (7)	0.061 (4)	0.080 (6)	−0.040 (5)	0.023 (5)	0.006 (4)
C13	0.046 (3)	0.051 (3)	0.043 (3)	−0.004 (3)	−0.007 (3)	0.010 (3)
C14	0.042 (3)	0.048 (3)	0.048 (3)	0.001 (3)	−0.007 (3)	0.006 (3)
C15	0.048 (3)	0.060 (4)	0.070 (4)	0.009 (3)	−0.010 (3)	0.007 (4)
C16	0.052 (3)	0.049 (4)	0.071 (5)	0.016 (3)	−0.007 (3)	−0.005 (3)
C17	0.052 (3)	0.049 (3)	0.063 (4)	−0.002 (3)	0.003 (3)	−0.004 (3)
C18	0.044 (3)	0.043 (3)	0.047 (4)	−0.003 (2)	0.004 (3)	−0.003 (3)
C19	0.043 (3)	0.042 (3)	0.040 (3)	−0.004 (2)	0.000 (3)	0.007 (3)
C20	0.044 (3)	0.044 (3)	0.036 (3)	−0.005 (3)	−0.006 (3)	0.007 (3)
C21	0.056 (4)	0.066 (4)	0.042 (4)	0.002 (3)	−0.001 (3)	−0.005 (3)
C22	0.090 (5)	0.079 (5)	0.061 (4)	0.005 (4)	−0.019 (4)	−0.002 (4)
O15	0.129 (5)	0.129 (5)	0.213 (12)	0.008 (7)	−0.052 (6)	−0.052 (6)
C45	0.12 (3)	0.17 (3)	0.31 (3)	0.01 (2)	−0.05 (2)	−0.060 (18)
O16	0.29 (3)	0.36 (4)	0.29 (2)	0.04 (3)	0.001 (18)	−0.01 (2)
C46	0.139 (14)	0.155 (19)	0.27 (2)	0.004 (12)	−0.041 (15)	−0.074 (16)
C47	0.143 (19)	0.118 (13)	0.26 (2)	0.016 (12)	−0.084 (15)	−0.086 (13)
C48	0.17 (2)	0.24 (5)	0.33 (5)	0.03 (3)	−0.06 (3)	−0.15 (3)

Geometric parameters (Å, º)

S1—O1	1.436 (5)	C10—C11	1.487 (9)
S1—O2	1.437 (4)	C11—H11A	0.9600
S1—C2	1.768 (5)	C11—H11B	0.9600
S1—C3	1.737 (6)	C11—H11C	0.9600
O3—C8	1.373 (7)	C12—H12A	0.9600
O3—C10	1.431 (7)	C12—H12B	0.9600
O4—C7	1.379 (7)	C12—H12C	0.9600
O4—C12	1.438 (7)	C13—C14	1.484 (8)
O5—C13	1.208 (6)	C14—C15	1.390 (8)
O6—C20	1.216 (6)	C14—C19	1.386 (7)
O7—C21	1.222 (7)	C15—H15	0.9300
N1—C1	1.474 (6)	C15—C16	1.380 (9)
N1—C13	1.402 (7)	C16—H16	0.9300
N1—C20	1.396 (7)	C16—C17	1.369 (8)
N2—H2	0.8597	C17—H17	0.9300
N2—C18	1.401 (7)	C17—C18	1.406 (7)
N2—C21	1.346 (7)	C18—C19	1.391 (7)
C1—H1	0.9800	C19—C20	1.468 (7)
C1—C2	1.522 (7)	C21—C22	1.496 (8)
C1—C4	1.526 (7)	C22—H22A	0.9600
C2—H2A	0.9700	C22—H22B	0.9600
C2—H2B	0.9700	C22—H22C	0.9600
C3—H3A	0.9600	O15—C46	1.34 (3)
C3—H3B	0.9600	O15—C47	1.34 (2)
C3—H3C	0.9600	C45—H45A	0.9600
C4—C5	1.361 (7)	C45—H45B	0.9600
C4—C9	1.399 (8)	C45—H45C	0.9600
C5—H5	0.9300	C45—C46	1.54 (2)
C5—C6	1.399 (8)	O16—C46	1.37 (4)
C6—H6	0.9300	C47—H47A	0.9700
C6—C7	1.369 (8)	C47—H47B	0.9700
C7—C8	1.398 (8)	C47—C48	1.56 (2)
C8—C9	1.379 (7)	C48—H48A	0.9600
C9—H9	0.9300	C48—H48B	0.9600
C10—H10A	0.9700	C48—H48C	0.9600
C10—H10B	0.9700
O1—S1—O2	118.1 (3)	O4—C12—H12A	109.5
O1—S1—C2	108.6 (3)	O4—C12—H12B	109.5
O1—S1—C3	108.8 (3)	O4—C12—H12C	109.5
O2—S1—C2	108.8 (3)	H12A—C12—H12B	109.5
O2—S1—C3	108.6 (3)	H12A—C12—H12C	109.5
C3—S1—C2	102.8 (3)	H12B—C12—H12C	109.5
C8—O3—C10	117.8 (4)	O5—C13—N1	124.7 (5)
C7—O4—C12	115.4 (5)	O5—C13—C14	128.7 (5)
C13—N1—C1	125.7 (4)	N1—C13—C14	106.6 (5)
C20—N1—C1	123.9 (4)	C15—C14—C13	129.9 (5)
C20—N1—C13	110.2 (4)	C19—C14—C13	107.8 (5)
C18—N2—H2	115.3	C19—C14—C15	122.3 (6)
C21—N2—H2	115.6	C14—C15—H15	122.1
C21—N2—C18	129.0 (5)	C16—C15—C14	115.7 (6)
N1—C1—H1	107.1	C16—C15—H15	122.1
N1—C1—C2	111.0 (4)	C15—C16—H16	118.2
N1—C1—C4	112.5 (4)	C17—C16—C15	123.6 (5)
C2—C1—H1	107.1	C17—C16—H16	118.2
C2—C1—C4	111.6 (4)	C16—C17—H17	119.7
C4—C1—H1	107.1	C16—C17—C18	120.5 (6)
S1—C2—H2A	108.6	C18—C17—H17	119.7
S1—C2—H2B	108.6	N2—C18—C17	125.3 (5)
C1—C2—S1	114.4 (4)	C19—C18—N2	117.8 (5)
C1—C2—H2A	108.6	C19—C18—C17	116.9 (5)
C1—C2—H2B	108.6	C14—C19—C18	121.1 (5)
H2A—C2—H2B	107.6	C14—C19—C20	108.1 (5)
S1—C3—H3A	109.5	C18—C19—C20	130.9 (5)
S1—C3—H3B	109.5	O6—C20—N1	124.2 (5)
S1—C3—H3C	109.5	O6—C20—C19	128.4 (5)
H3A—C3—H3B	109.5	N1—C20—C19	107.4 (4)
H3A—C3—H3C	109.5	O7—C21—N2	123.2 (6)
H3B—C3—H3C	109.5	O7—C21—C22	121.7 (6)
C5—C4—C1	119.2 (5)	N2—C21—C22	115.1 (6)
C5—C4—C9	118.3 (5)	C21—C22—H22A	109.5
C9—C4—C1	122.6 (5)	C21—C22—H22B	109.5
C4—C5—H5	119.4	C21—C22—H22C	109.5
C4—C5—C6	121.2 (5)	H22A—C22—H22B	109.5
C6—C5—H5	119.4	H22A—C22—H22C	109.5
C5—C6—H6	119.9	H22B—C22—H22C	109.5
C7—C6—C5	120.1 (5)	C46—O15—C47	118 (2)
C7—C6—H6	119.9	H45A—C45—H45B	109.5
O4—C7—C8	115.6 (5)	H45A—C45—H45C	109.5
C6—C7—O4	124.6 (5)	H45B—C45—H45C	109.5
C6—C7—C8	119.7 (5)	C46—C45—H45A	109.5
O3—C8—C7	116.2 (5)	C46—C45—H45B	109.5
O3—C8—C9	124.6 (5)	C46—C45—H45C	109.5
C9—C8—C7	119.3 (6)	O15—C46—C45	116 (3)
C4—C9—H9	119.3	O15—C46—O16	109 (3)
C8—C9—C4	121.4 (5)	O16—C46—C45	133 (4)
C8—C9—H9	119.3	O15—C47—H47A	111.5
O3—C10—H10A	109.9	O15—C47—H47B	111.5
O3—C10—H10B	109.9	O15—C47—C48	101 (2)
O3—C10—C11	109.1 (5)	H47A—C47—H47B	109.3
H10A—C10—H10B	108.3	C48—C47—H47A	111.5
C11—C10—H10A	109.9	C48—C47—H47B	111.5
C11—C10—H10B	109.9	C47—C48—H48A	109.5
C10—C11—H11A	109.5	C47—C48—H48B	109.5
C10—C11—H11B	109.5	C47—C48—H48C	109.5
C10—C11—H11C	109.5	H48A—C48—H48B	109.5
H11A—C11—H11B	109.5	H48A—C48—H48C	109.5
H11A—C11—H11C	109.5	H48B—C48—H48C	109.5
H11B—C11—H11C	109.5
O1—S1—C2—C1	58.1 (5)	C10—O3—C8—C9	−4.0 (8)
O2—S1—C2—C1	−71.7 (5)	C12—O4—C7—C6	6.5 (9)
O3—C8—C9—C4	−179.9 (5)	C12—O4—C7—C8	−174.7 (6)
O4—C7—C8—O3	1.6 (8)	C13—N1—C1—C2	54.0 (6)
O4—C7—C8—C9	−179.0 (5)	C13—N1—C1—C4	−71.9 (6)
O5—C13—C14—C15	−0.1 (10)	C13—N1—C20—O6	179.6 (5)
O5—C13—C14—C19	179.8 (6)	C13—N1—C20—C19	−0.4 (6)
N1—C1—C2—S1	61.0 (5)	C13—C14—C15—C16	179.8 (6)
N1—C1—C4—C5	−78.2 (6)	C13—C14—C19—C18	−179.7 (5)
N1—C1—C4—C9	102.4 (6)	C13—C14—C19—C20	0.6 (6)
N1—C13—C14—C15	179.3 (6)	C14—C15—C16—C17	0.0 (9)
N1—C13—C14—C19	−0.8 (6)	C14—C19—C20—O6	179.9 (5)
N2—C18—C19—C14	178.1 (5)	C14—C19—C20—N1	−0.2 (6)
N2—C18—C19—C20	−2.3 (9)	C15—C14—C19—C18	0.1 (8)
C1—N1—C13—O5	4.6 (8)	C15—C14—C19—C20	−179.5 (5)
C1—N1—C13—C14	−174.8 (5)	C15—C16—C17—C18	0.1 (10)
C1—N1—C20—O6	−4.8 (8)	C16—C17—C18—N2	−178.1 (6)
C1—N1—C20—C19	175.2 (4)	C16—C17—C18—C19	−0.1 (8)
C1—C4—C5—C6	−177.7 (5)	C17—C18—C19—C14	0.0 (8)
C1—C4—C9—C8	177.8 (5)	C17—C18—C19—C20	179.5 (5)
C2—C1—C4—C5	156.3 (5)	C18—N2—C21—O7	−6.1 (10)
C2—C1—C4—C9	−23.2 (7)	C18—N2—C21—C22	173.5 (6)
C3—S1—C2—C1	173.3 (4)	C18—C19—C20—O6	0.3 (10)
C4—C1—C2—S1	−172.6 (4)	C18—C19—C20—N1	−179.8 (5)
C4—C5—C6—C7	−1.2 (9)	C19—C14—C15—C16	−0.1 (9)
C5—C4—C9—C8	−1.7 (8)	C20—N1—C1—C2	−120.9 (5)
C5—C6—C7—O4	179.0 (5)	C20—N1—C1—C4	113.2 (5)
C5—C6—C7—C8	0.2 (9)	C20—N1—C13—O5	−179.8 (5)
C6—C7—C8—O3	−179.4 (5)	C20—N1—C13—C14	0.7 (6)
C6—C7—C8—C9	−0.1 (9)	C21—N2—C18—C17	−0.4 (9)
C7—C8—C9—C4	0.8 (8)	C21—N2—C18—C19	−178.4 (6)
C8—O3—C10—C11	−176.3 (6)	C46—O15—C47—C48	−177 (4)
C9—C4—C5—C6	1.9 (8)	C47—O15—C46—C45	174 (5)
C10—O3—C8—C7	175.3 (5)	C47—O15—C46—O16	7 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O6	0.86	2.29	2.974 (6)	136
C2—H2A···O5^i	0.97	2.33	3.171 (7)	145
C2—H2A···O5	0.97	2.46	3.087 (7)	122
C2—H2B···O7^ii	0.97	2.56	3.524 (7)	173
C3—H3A···O6^iii	0.96	2.44	3.132 (7)	129
C3—H3B···O2^i	0.96	2.65	3.476 (9)	145
C6—H6···O1^ii	0.93	2.49	3.403 (8)	167
C9—H9···O5^i	0.93	2.48	3.408 (7)	177
C12—H12A···O7^iv	0.96	2.65	3.595 (9)	169
C17—H17···O7	0.93	2.31	2.896 (8)	120

Symmetry codes: (i) y, x, −z+1; (ii) −x+3/2, y−1/2, −z+5/4; (iii) y+1/2, −x+3/2, z−1/4; (iv) y−1/2, −x+1/2, z−1/4.

(2) (S)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-4-acetamidoisoindoline-1,3-dione toluene hemisolvate

Crystal data

C22H24N2O7S·0.5C7H8	Dx = 1.343 Mg m^−3
Mr = 506.56	Mo Kα radiation, λ = 0.71073 Å
Tetragonal, P41212	Cell parameters from 25 reflections
a = 12.980 (3) Å	θ = 9–12°
c = 29.734 (6) Å	µ = 0.18 mm^−1
V = 5010 (3) Å^3	T = 293 K
Z = 8	Block, colourless
F(000) = 2136	0.2 × 0.1 × 0.1 mm

Data collection

Enraf–Nonius CAD-4 diffractometer	θmax = 25.0°, θmin = 1.7°
ω/2θ scans	h = −15→15
7337 measured reflections	k = −15→0
4433 independent reflections	l = −35→0
1916 reflections with I > 2σ(I)	1 standard reflections every 60 reflections
Rint = 0.099	intensity decay: 1%

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.099	w = 1/[σ^2(Fo^2) + (0.0625P)^2] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.224	(Δ/σ)max < 0.001
S = 1.01	Δρmax = 0.27 e Å^−3
4433 reflections	Δρmin = −0.26 e Å^−3
321 parameters	Absolute structure: Flack x determined using 403 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
87 restraints	Absolute structure parameter: −0.1 (2)
Primary atom site location: dual

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.

Refinement. 1. Fixed Uiso At 1.2 times of: All C(H) groups, All C(H,H) groups, All N(H) groups At 1.5 times of: All C(H,H,H) groups 2. Uiso/Uaniso restraints and constraints Uanis(C48) ~Ueq, Uanis(C45) ~Ueq, Uanis(C46) ~Ueq, Uanis(C50) ~Ueq, Uanis(C47) ~Ueq, Uanis(C49) ~Ueq, Uanis(C51) ~Ueq: with sigma of 0.01 and sigma for terminal atoms of 0.02 3. Rigid body (RIGU) restrains C45, C46, C47, C48, C49, C50, C51 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004 4. Others Fixed Sof: C45(0.5) H45(0.5) C46(0.5) H46(0.5) C47(0.5) H47(0.5) C48(0.5) H48(0.5) C49(0.5) H49(0.5) C50(0.5) C51(0.5) H51A(0.5) H51B(0.5) H51C(0.5) 5.a Ternary CH refined with riding coordinates: C1(H1) 5.b Secondary CH2 refined with riding coordinates: C2(H2A,H2B), C10(H10A,H10B) 5.c Aromatic/amide H refined with riding coordinates: N2(H2), C5(H5), C8(H8), C9(H9), C15(H15), C16(H16), C17(H17), C45(H45), C46(H46), C47(H47), C48(H48), C49(H49) 5.d Fitted hexagon refined as free rotating group: C4(C5,C6,C7,C8,C9), C14(C15,C16,C17,C18,C19), C45(C46,C47,C48,C49,C50) 5.e Idealised Me refined as rotating group: C3(H3A,H3B,H3C), C11(H11A,H11B,H11C), C12(H12A,H12B,H12C), C22(H22A,H22B, H22C), C51(H51A,H51B,H51C)

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
S1	0.1605 (2)	0.5996 (2)	0.71358 (10)	0.0541 (7)
O1	0.2073 (5)	0.6918 (5)	0.6956 (2)	0.069 (2)
O2	0.0732 (5)	0.5572 (5)	0.6882 (3)	0.070 (2)
O3	0.5370 (5)	0.2469 (5)	0.7659 (2)	0.069 (2)
O4	0.5544 (5)	0.1111 (5)	0.7012 (3)	0.077 (2)
O5	0.4666 (5)	0.6011 (6)	0.6956 (2)	0.063 (2)
O6	0.2364 (5)	0.5239 (5)	0.5839 (2)	0.056 (2)
O7	0.3242 (5)	0.7975 (5)	0.4604 (3)	0.072 (2)
N1	0.3419 (5)	0.5391 (6)	0.6464 (3)	0.041 (2)
N2	0.2963 (6)	0.6819 (6)	0.5156 (3)	0.054 (2)
H2	0.2590	0.6293	0.5223	0.065*
C1	0.2935 (7)	0.4604 (7)	0.6750 (4)	0.054 (3)
H1	0.2328	0.4347	0.6589	0.064*
C2	0.2560 (7)	0.5033 (7)	0.7203 (3)	0.053 (3)
H2A	0.3142	0.5321	0.7365	0.063*
H2B	0.2282	0.4474	0.7382	0.063*
C3	0.1219 (9)	0.6235 (8)	0.7696 (4)	0.085 (4)
H3A	0.1816	0.6369	0.7877	0.128*
H3B	0.0862	0.5644	0.7811	0.128*
H3C	0.0770	0.6823	0.7703	0.128*
C4	0.3668 (3)	0.3676 (3)	0.68242 (18)	0.042 (2)
C5	0.4197 (4)	0.3525 (4)	0.72254 (17)	0.049 (3)
H5	0.4129	0.3999	0.7458	0.058*
C6	0.4827 (5)	0.2668 (4)	0.72783 (19)	0.052 (3)
C7	0.4929 (4)	0.1961 (3)	0.6930 (2)	0.051 (3)
C8	0.4400 (5)	0.2111 (4)	0.6529 (2)	0.058 (3)
H8	0.4468	0.1638	0.6296	0.070*
C9	0.3770 (4)	0.2968 (4)	0.64759 (16)	0.055 (3)
H9	0.3416	0.3069	0.6208	0.066*
C10	0.5370 (8)	0.3212 (8)	0.8012 (4)	0.073 (4)
H10A	0.4688	0.3254	0.8145	0.087*
H10B	0.5544	0.3884	0.7892	0.087*
C11	0.6137 (10)	0.2914 (9)	0.8365 (4)	0.104 (5)
H11A	0.6797	0.2806	0.8228	0.155*
H11B	0.5916	0.2291	0.8510	0.155*
H11C	0.6188	0.3455	0.8584	0.155*
C12	0.5718 (11)	0.0421 (9)	0.6639 (4)	0.106 (5)
H12A	0.6046	0.0789	0.6398	0.160*
H12B	0.5071	0.0151	0.6536	0.160*
H12C	0.6153	−0.0136	0.6734	0.160*
C13	0.4202 (7)	0.6045 (8)	0.6600 (4)	0.055 (3)
C14	0.4363 (4)	0.6793 (4)	0.62356 (17)	0.049 (3)
C15	0.5047 (4)	0.7609 (4)	0.6183 (2)	0.064 (3)
H15	0.5510	0.7768	0.6411	0.077*
C16	0.5038 (4)	0.8185 (4)	0.5789 (2)	0.068 (4)
H16	0.5495	0.8731	0.5753	0.082*
C17	0.4346 (5)	0.7946 (5)	0.54477 (19)	0.060 (3)
H17	0.4340	0.8332	0.5184	0.071*
C18	0.3662 (4)	0.7131 (5)	0.55005 (18)	0.049 (3)
C19	0.3671 (4)	0.6554 (4)	0.58945 (19)	0.044 (3)
C20	0.3052 (7)	0.5686 (7)	0.6042 (3)	0.043 (2)
C21	0.2791 (7)	0.7213 (8)	0.4743 (4)	0.059 (3)
C22	0.2084 (8)	0.6592 (8)	0.4454 (4)	0.074 (4)
H22A	0.1902	0.6983	0.4192	0.110*
H22B	0.1472	0.6425	0.4620	0.110*
H22C	0.2424	0.5968	0.4364	0.110*
C45	0.5776 (13)	0.5377 (13)	0.5355 (7)	0.091 (5)	0.5
H45	0.6262	0.5619	0.5560	0.110*	0.5
C46	0.5124 (16)	0.4572 (14)	0.5474 (7)	0.097 (6)	0.5
H46	0.5173	0.4276	0.5758	0.117*	0.5
C47	0.440 (2)	0.421 (2)	0.5168 (8)	0.089 (6)	0.5
H47	0.3962	0.3673	0.5248	0.107*	0.5
C48	0.4325 (19)	0.465 (2)	0.4744 (8)	0.103 (6)	0.5
H48	0.3840	0.4413	0.4540	0.124*	0.5
C49	0.4978 (17)	0.5459 (17)	0.4625 (7)	0.110 (6)	0.5
H49	0.4929	0.5756	0.4342	0.132*	0.5
C50	0.5703 (15)	0.5820 (14)	0.4931 (8)	0.096 (5)	0.5
C51	0.630 (2)	0.669 (2)	0.4782 (10)	0.148 (9)	0.5
H51A	0.6307	0.7207	0.5011	0.222*	0.5
H51B	0.6006	0.6964	0.4512	0.222*	0.5
H51C	0.6997	0.6469	0.4722	0.222*	0.5

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0502 (15)	0.0470 (14)	0.0652 (17)	0.0127 (13)	0.0022 (15)	0.0027 (15)
O1	0.080 (5)	0.052 (4)	0.075 (6)	0.003 (4)	0.012 (4)	0.020 (4)
O2	0.040 (4)	0.075 (5)	0.096 (6)	−0.002 (4)	−0.010 (4)	0.015 (4)
O3	0.076 (5)	0.055 (4)	0.075 (5)	0.009 (4)	−0.025 (4)	−0.008 (4)
O4	0.074 (5)	0.056 (4)	0.100 (7)	0.018 (4)	−0.008 (5)	−0.008 (5)
O5	0.049 (4)	0.076 (5)	0.065 (5)	−0.012 (4)	0.000 (4)	−0.015 (4)
O6	0.054 (4)	0.052 (4)	0.062 (5)	−0.008 (3)	−0.014 (4)	0.001 (4)
O7	0.069 (5)	0.074 (5)	0.071 (5)	−0.011 (4)	−0.008 (4)	0.024 (4)
N1	0.030 (4)	0.039 (4)	0.054 (5)	−0.003 (3)	−0.006 (4)	−0.005 (4)
N2	0.045 (5)	0.059 (5)	0.058 (6)	−0.007 (4)	−0.011 (4)	0.007 (4)
C1	0.045 (6)	0.047 (6)	0.069 (7)	−0.010 (5)	−0.008 (6)	0.002 (6)
C2	0.052 (6)	0.034 (5)	0.072 (7)	0.013 (4)	−0.004 (6)	0.009 (5)
C3	0.122 (10)	0.068 (8)	0.065 (8)	0.032 (7)	0.026 (7)	−0.006 (6)
C4	0.043 (6)	0.028 (5)	0.056 (6)	−0.005 (4)	−0.002 (5)	−0.005 (4)
C5	0.046 (6)	0.035 (5)	0.065 (7)	0.000 (4)	0.000 (5)	−0.009 (5)
C6	0.060 (7)	0.042 (6)	0.054 (7)	−0.004 (5)	−0.006 (5)	−0.005 (5)
C7	0.065 (6)	0.023 (5)	0.065 (7)	−0.011 (5)	−0.013 (6)	−0.001 (5)
C8	0.051 (6)	0.047 (6)	0.076 (8)	−0.001 (5)	0.017 (6)	−0.014 (6)
C9	0.060 (7)	0.027 (5)	0.077 (8)	0.007 (5)	−0.007 (6)	0.002 (5)
C10	0.084 (8)	0.068 (7)	0.067 (8)	−0.005 (7)	−0.028 (7)	−0.015 (7)
C11	0.139 (12)	0.077 (9)	0.094 (10)	0.012 (9)	−0.047 (9)	−0.021 (8)
C12	0.152 (12)	0.068 (8)	0.099 (11)	0.058 (8)	0.032 (9)	−0.027 (7)
C13	0.037 (6)	0.055 (6)	0.072 (8)	−0.003 (5)	−0.008 (5)	−0.016 (6)
C14	0.050 (6)	0.038 (6)	0.058 (7)	−0.001 (5)	0.005 (5)	−0.002 (5)
C15	0.047 (6)	0.051 (6)	0.094 (9)	−0.007 (6)	0.003 (6)	−0.002 (6)
C16	0.040 (6)	0.059 (7)	0.105 (10)	−0.011 (6)	−0.005 (6)	0.000 (7)
C17	0.046 (6)	0.046 (6)	0.087 (9)	−0.010 (5)	0.011 (6)	0.019 (6)
C18	0.036 (5)	0.049 (6)	0.062 (7)	0.005 (5)	0.007 (5)	0.014 (5)
C19	0.038 (5)	0.031 (5)	0.064 (7)	−0.005 (4)	0.013 (5)	0.002 (5)
C20	0.045 (5)	0.039 (5)	0.046 (6)	0.012 (5)	−0.005 (5)	−0.005 (5)
C21	0.038 (6)	0.064 (7)	0.074 (8)	0.001 (5)	0.007 (6)	0.000 (6)
C22	0.067 (7)	0.068 (7)	0.086 (9)	0.004 (6)	−0.011 (7)	−0.003 (7)
C45	0.081 (9)	0.083 (8)	0.110 (8)	0.015 (7)	0.021 (6)	−0.017 (6)
C46	0.089 (9)	0.094 (9)	0.109 (9)	0.007 (7)	0.009 (7)	−0.010 (7)
C47	0.080 (9)	0.087 (9)	0.100 (8)	0.017 (7)	0.012 (6)	−0.016 (6)
C48	0.102 (10)	0.101 (9)	0.107 (8)	0.015 (7)	0.011 (7)	−0.010 (7)
C49	0.109 (9)	0.104 (9)	0.118 (9)	0.013 (7)	0.016 (7)	−0.012 (7)
C50	0.093 (8)	0.090 (8)	0.104 (8)	0.020 (6)	0.023 (6)	−0.018 (6)
C51	0.158 (15)	0.125 (12)	0.161 (17)	−0.012 (10)	0.034 (12)	−0.002 (10)

Geometric parameters (Å, º)

S1—O1	1.445 (7)	C11—H11A	0.9600
S1—O2	1.468 (7)	C11—H11B	0.9600
S1—C2	1.772 (9)	C11—H11C	0.9600
S1—C3	1.766 (11)	C12—H12A	0.9600
O3—C6	1.359 (8)	C12—H12B	0.9600
O3—C10	1.425 (11)	C12—H12C	0.9600
O4—C7	1.384 (8)	C13—C14	1.470 (12)
O4—C12	1.443 (12)	C14—C15	1.3900
O5—C13	1.219 (11)	C14—C19	1.3900
O6—C20	1.225 (10)	C15—H15	0.9300
O7—C21	1.222 (11)	C15—C16	1.3900
N1—C1	1.469 (12)	C16—H16	0.9300
N1—C13	1.386 (11)	C16—C17	1.3900
N1—C20	1.395 (11)	C17—H17	0.9300
N2—H2	0.8600	C17—C18	1.3900
N2—C18	1.427 (9)	C18—C19	1.3900
N2—C21	1.348 (12)	C19—C20	1.451 (10)
C1—H1	0.9800	C21—C22	1.494 (13)
C1—C2	1.539 (13)	C22—H22A	0.9600
C1—C4	1.552 (10)	C22—H22B	0.9600
C2—H2A	0.9700	C22—H22C	0.9600
C2—H2B	0.9700	C45—H45	0.9300
C3—H3A	0.9600	C45—C46	1.3900
C3—H3B	0.9600	C45—C50	1.3900
C3—H3C	0.9600	C46—H46	0.9300
C4—C5	1.3900	C46—C47	1.3900
C4—C9	1.3900	C47—H47	0.9300
C5—H5	0.9300	C47—C48	1.3900
C5—C6	1.3900	C48—H48	0.9300
C6—C7	1.3900	C48—C49	1.3900
C7—C8	1.3900	C49—H49	0.9300
C8—H8	0.9300	C49—C50	1.3900
C8—C9	1.3900	C50—C51	1.44 (3)
C9—H9	0.9300	C51—H51A	0.9600
C10—H10A	0.9700	C51—H51B	0.9600
C10—H10B	0.9700	C51—H51C	0.9600
C10—C11	1.497 (14)
O1—S1—O2	116.4 (4)	O4—C12—H12B	109.5
O1—S1—C2	109.4 (4)	O4—C12—H12C	109.5
O1—S1—C3	108.8 (5)	H12A—C12—H12B	109.5
O2—S1—C2	109.6 (4)	H12A—C12—H12C	109.5
O2—S1—C3	109.4 (5)	H12B—C12—H12C	109.5
C3—S1—C2	102.4 (5)	O5—C13—N1	126.5 (10)
C6—O3—C10	119.1 (7)	O5—C13—C14	126.5 (9)
C7—O4—C12	116.8 (8)	N1—C13—C14	107.1 (8)
C13—N1—C1	124.7 (8)	C15—C14—C13	132.6 (5)
C13—N1—C20	110.2 (8)	C15—C14—C19	120.0
C20—N1—C1	124.4 (7)	C19—C14—C13	107.4 (5)
C18—N2—H2	114.7	C14—C15—H15	120.0
C21—N2—H2	114.7	C16—C15—C14	120.0
C21—N2—C18	130.6 (8)	C16—C15—H15	120.0
N1—C1—H1	107.3	C15—C16—H16	120.0
N1—C1—C2	113.1 (8)	C15—C16—C17	120.0
N1—C1—C4	111.1 (7)	C17—C16—H16	120.0
C2—C1—H1	107.3	C16—C17—H17	120.0
C2—C1—C4	110.4 (7)	C18—C17—C16	120.0
C4—C1—H1	107.3	C18—C17—H17	120.0
S1—C2—H2A	109.2	C17—C18—N2	122.7 (5)
S1—C2—H2B	109.2	C19—C18—N2	117.2 (5)
C1—C2—S1	112.1 (7)	C19—C18—C17	120.0
C1—C2—H2A	109.2	C14—C19—C20	108.1 (5)
C1—C2—H2B	109.2	C18—C19—C14	120.0
H2A—C2—H2B	107.9	C18—C19—C20	131.9 (5)
S1—C3—H3A	109.5	O6—C20—N1	124.2 (8)
S1—C3—H3B	109.5	O6—C20—C19	128.5 (8)
S1—C3—H3C	109.5	N1—C20—C19	107.2 (7)
H3A—C3—H3B	109.5	O7—C21—N2	122.4 (10)
H3A—C3—H3C	109.5	O7—C21—C22	122.4 (10)
H3B—C3—H3C	109.5	N2—C21—C22	114.9 (9)
C5—C4—C1	122.3 (5)	C21—C22—H22A	109.5
C5—C4—C9	120.0	C21—C22—H22B	109.5
C9—C4—C1	117.7 (5)	C21—C22—H22C	109.5
C4—C5—H5	120.0	H22A—C22—H22B	109.5
C6—C5—C4	120.0	H22A—C22—H22C	109.5
C6—C5—H5	120.0	H22B—C22—H22C	109.5
O3—C6—C5	123.5 (5)	C46—C45—H45	120.0
O3—C6—C7	116.5 (5)	C46—C45—C50	120.0
C5—C6—C7	120.0	C50—C45—H45	120.0
O4—C7—C6	116.8 (5)	C45—C46—H46	120.0
O4—C7—C8	123.2 (5)	C47—C46—C45	120.0
C8—C7—C6	120.0	C47—C46—H46	120.0
C7—C8—H8	120.0	C46—C47—H47	120.0
C7—C8—C9	120.0	C48—C47—C46	120.0
C9—C8—H8	120.0	C48—C47—H47	120.0
C4—C9—H9	120.0	C47—C48—H48	120.0
C8—C9—C4	120.0	C47—C48—C49	120.0
C8—C9—H9	120.0	C49—C48—H48	120.0
O3—C10—H10A	109.7	C48—C49—H49	120.0
O3—C10—H10B	109.7	C48—C49—C50	120.0
O3—C10—C11	110.0 (9)	C50—C49—H49	120.0
H10A—C10—H10B	108.2	C45—C50—C51	124.5 (17)
C11—C10—H10A	109.7	C49—C50—C45	120.0
C11—C10—H10B	109.7	C49—C50—C51	115.4 (17)
C10—C11—H11A	109.5	C50—C51—H51A	109.5
C10—C11—H11B	109.5	C50—C51—H51B	109.5
C10—C11—H11C	109.5	C50—C51—H51C	109.5
H11A—C11—H11B	109.5	H51A—C51—H51B	109.5
H11A—C11—H11C	109.5	H51A—C51—H51C	109.5
H11B—C11—H11C	109.5	H51B—C51—H51C	109.5
O4—C12—H12A	109.5
O1—S1—C2—C1	−71.1 (8)	C13—N1—C1—C2	51.6 (12)
O2—S1—C2—C1	57.6 (8)	C13—N1—C1—C4	−73.3 (11)
O3—C6—C7—O4	2.1 (6)	C13—N1—C20—O6	179.5 (9)
O3—C6—C7—C8	−179.9 (6)	C13—N1—C20—C19	2.5 (10)
O4—C7—C8—C9	177.9 (6)	C13—C14—C15—C16	178.6 (7)
O5—C13—C14—C15	1.5 (14)	C13—C14—C19—C18	−178.9 (5)
O5—C13—C14—C19	−179.7 (9)	C13—C14—C19—C20	1.7 (6)
N1—C1—C2—S1	61.7 (9)	C14—C15—C16—C17	0.0
N1—C1—C4—C5	104.0 (7)	C14—C19—C20—O6	−179.4 (8)
N1—C1—C4—C9	−77.4 (8)	C14—C19—C20—N1	−2.6 (7)
N1—C13—C14—C15	−178.9 (5)	C15—C14—C19—C18	0.0
N1—C13—C14—C19	−0.2 (8)	C15—C14—C19—C20	−179.4 (5)
N2—C18—C19—C14	177.4 (6)	C15—C16—C17—C18	0.0
N2—C18—C19—C20	−3.3 (7)	C16—C17—C18—N2	−177.3 (6)
C1—N1—C13—O5	7.0 (16)	C16—C17—C18—C19	0.0
C1—N1—C13—C14	−172.6 (7)	C17—C18—C19—C14	0.0
C1—N1—C20—O6	−9.3 (14)	C17—C18—C19—C20	179.2 (7)
C1—N1—C20—C19	173.6 (7)	C18—N2—C21—O7	−1.8 (16)
C1—C4—C5—C6	178.6 (5)	C18—N2—C21—C22	172.6 (8)
C1—C4—C9—C8	−178.7 (5)	C18—C19—C20—O6	1.2 (13)
C2—C1—C4—C5	−22.3 (9)	C18—C19—C20—N1	178.1 (5)
C2—C1—C4—C9	156.3 (6)	C19—C14—C15—C16	0.0
C3—S1—C2—C1	173.6 (7)	C20—N1—C1—C2	−118.3 (9)
C4—C1—C2—S1	−173.1 (5)	C20—N1—C1—C4	116.9 (9)
C4—C5—C6—O3	179.9 (7)	C20—N1—C13—O5	178.1 (10)
C4—C5—C6—C7	0.0	C20—N1—C13—C14	−1.5 (10)
C5—C4—C9—C8	0.0	C21—N2—C18—C17	−1.9 (12)
C5—C6—C7—O4	−178.1 (6)	C21—N2—C18—C19	−179.2 (8)
C5—C6—C7—C8	0.0	C45—C46—C47—C48	0.0
C6—O3—C10—C11	−171.3 (9)	C46—C45—C50—C49	0.0
C6—C7—C8—C9	0.0	C46—C45—C50—C51	177 (3)
C7—C8—C9—C4	0.0	C46—C47—C48—C49	0.0
C9—C4—C5—C6	0.0	C47—C48—C49—C50	0.0
C10—O3—C6—C5	−5.5 (10)	C48—C49—C50—C45	0.0
C10—O3—C6—C7	174.4 (7)	C48—C49—C50—C51	−177 (2)
C12—O4—C7—C6	−175.0 (7)	C50—C45—C46—C47	0.0
C12—O4—C7—C8	7.0 (10)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O6	0.86	2.30	2.988 (10)	137
C2—H2A···O5^i	0.97	2.30	3.135 (12)	144
C2—H2A···O5	0.97	2.49	3.101 (12)	121
C2—H2B···O7^ii	0.97	2.56	3.530 (12)	173
C3—H3A···O1^i	0.96	2.65	3.427 (14)	138
C3—H3C···O6^iii	0.96	2.40	3.063 (12)	126
C5—H5···O5^i	0.93	2.46	3.392 (8)	177
C8—H8···O2^ii	0.93	2.46	3.370 (9)	167
C12—H12C···O7^iv	0.96	2.63	3.576 (13)	168
C17—H17···O7	0.93	2.28	2.889 (9)	122

Symmetry codes: (i) −y+1, −x+1, −z+3/2; (ii) −x+1/2, y−1/2, −z+5/4; (iii) −y+1/2, x+1/2, z+1/4; (iv) −y+3/2, x−1/2, z+1/4.

(3) (S)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-4-acetamidoisoindoline-1,3-dione dichloromethane monosolvate

Crystal data

C22H24N2O7S·CH2Cl2	Dx = 1.415 Mg m^−3
Mr = 545.42	Mo Kα radiation, λ = 0.71073 Å
Tetragonal, P41212	Cell parameters from 25 reflections
a = 13.171 (3) Å	θ = 9–13°
c = 29.524 (6) Å	µ = 0.38 mm^−1
V = 5122 (3) Å^3	T = 293 K
Z = 8	Block, colourless
F(000) = 2272	0.3 × 0.2 × 0.1 mm

Data collection

Nonius CAD4 diffractometer	θmax = 25.4°, θmin = 1.7°
ω/2θ scans	h = −15→15
7753 measured reflections	k = 0→15
4697 independent reflections	l = 0→35
2736 reflections with I > 2σ(I)	1 standard reflections every 60 reflections
Rint = 0.051	intensity decay: 1%

Refinement

Refinement on F^2	Hydrogen site location: mixed
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.057	w = 1/[σ^2(Fo^2) + (0.0529P)^2] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.135	(Δ/σ)max < 0.001
S = 1.00	Δρmax = 0.20 e Å^−3
4697 reflections	Δρmin = −0.25 e Å^−3
321 parameters	Absolute structure: Flack x determined using 830 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
0 restraints	Absolute structure parameter: 0.17 (8)

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.

Refinement. 1. Fixed Uiso At 1.2 times of: All C(H) groups, All C(H,H) groups, All N(H) groups At 1.5 times of: All C(H,H,H) groups 2. Others Fixed Sof: H1A(0.5) H1B(0.5) H2A(0.5) H2B(0.5) 3.a Riding coordinates: N2(H2) 3.b Ternary CH refined with riding coordinates: C4(H4) 3.c Secondary CH2 refined with riding coordinates: C3(H3A,H3B), C18(H18A,H18B), C1(H1A,H1B), C2(H2A,H2B) 3.d Aromatic/amide H refined with riding coordinates: C10(H10), C11(H11), C12(H12), C16(H16), C22(H22), C23(H23) 3.e Idealised Me refined as rotating group: C9(H9A,H9B,H9C), C19(H19A,H19B,H19C), C21(H21A,H21B,H21C), C24(H24A,H24B,H24C)

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
S1	0.39269 (12)	0.15616 (12)	0.46154 (6)	0.0543 (4)
O1	0.4345 (3)	0.0717 (3)	0.43754 (16)	0.0723 (13)
O2	0.3043 (3)	0.2042 (3)	0.44290 (14)	0.0662 (12)
O3	0.4667 (3)	0.2359 (3)	0.33258 (14)	0.0544 (11)
O4	0.1944 (4)	0.3254 (4)	0.20964 (15)	0.0800 (14)
O5	0.3921 (3)	0.4565 (3)	0.44678 (14)	0.0596 (12)
O6	0.7385 (3)	0.5276 (3)	0.51867 (14)	0.0623 (12)
O7	0.8730 (3)	0.5441 (3)	0.45520 (15)	0.0666 (13)
N1	0.4514 (3)	0.3376 (3)	0.39610 (16)	0.0424 (11)
N2	0.3115 (4)	0.2972 (4)	0.26482 (16)	0.0525 (13)
H2	0.3637	0.2605	0.2710	0.063*
C3	0.4881 (4)	0.2491 (4)	0.4687 (2)	0.0460 (14)
H3A	0.4602	0.3054	0.4858	0.055*
H3B	0.5430	0.2201	0.4863	0.055*
C4	0.5314 (4)	0.2898 (4)	0.42417 (19)	0.0439 (14)
H4	0.5572	0.2313	0.4072	0.053*
C5	0.4243 (4)	0.3038 (4)	0.35334 (19)	0.0421 (13)
C6	0.3362 (4)	0.3651 (4)	0.3388 (2)	0.0435 (14)
C7	0.2816 (4)	0.3646 (4)	0.2989 (2)	0.0453 (14)
C8	0.2709 (5)	0.2823 (5)	0.2225 (2)	0.0574 (16)
C9	0.3289 (5)	0.2122 (5)	0.1929 (2)	0.0712 (19)
H9A	0.3408	0.1496	0.2086	0.107*
H9B	0.3927	0.2427	0.1850	0.107*
H9C	0.2906	0.1989	0.1658	0.107*
C10	0.2003 (4)	0.4329 (4)	0.2954 (2)	0.0557 (16)
H10	0.1618	0.4350	0.2691	0.067*
C11	0.1774 (5)	0.4966 (5)	0.3307 (3)	0.0630 (18)
H11	0.1221	0.5400	0.3278	0.076*
C12	0.2328 (4)	0.4993 (5)	0.3706 (2)	0.0588 (17)
H12	0.2173	0.5438	0.3940	0.071*
C13	0.3126 (4)	0.4316 (4)	0.37335 (19)	0.0451 (14)
C14	0.3859 (5)	0.4141 (4)	0.4104 (2)	0.0494 (15)
C15	0.6208 (4)	0.3604 (4)	0.4324 (2)	0.0453 (14)
C16	0.6344 (4)	0.4129 (4)	0.4729 (2)	0.0500 (15)
H16	0.5859	0.4067	0.4956	0.060*
C17	0.7186 (4)	0.4741 (4)	0.4801 (2)	0.0469 (14)
C18	0.6667 (5)	0.5196 (5)	0.5547 (2)	0.0628 (19)
H18A	0.6590	0.4492	0.5637	0.075*
H18B	0.6011	0.5449	0.5450	0.075*
C19	0.7052 (6)	0.5811 (7)	0.5937 (3)	0.101 (3)
H19A	0.6598	0.5741	0.6189	0.152*
H19B	0.7090	0.6512	0.5850	0.152*
H19C	0.7715	0.5575	0.6021	0.152*
C20	0.7910 (4)	0.4842 (4)	0.4452 (2)	0.0503 (15)
C21	0.9460 (5)	0.5585 (6)	0.4200 (2)	0.077 (2)
H21A	0.9996	0.6017	0.4307	0.116*
H21B	0.9137	0.5895	0.3943	0.116*
H21C	0.9737	0.4940	0.4113	0.116*
C22	0.7766 (4)	0.4332 (5)	0.4049 (2)	0.0533 (16)
H22	0.8241	0.4400	0.3818	0.064*
C23	0.6917 (4)	0.3715 (4)	0.3985 (2)	0.0512 (16)
H23	0.6830	0.3376	0.3711	0.061*
C24	0.3660 (6)	0.1209 (6)	0.5174 (2)	0.081 (2)
H24A	0.3401	0.1784	0.5336	0.122*
H24B	0.4270	0.0972	0.5317	0.122*
H24C	0.3163	0.0676	0.5174	0.122*
Cl1	0.8600 (2)	0.81065 (19)	0.45348 (11)	0.1396 (11)
C1	0.7849 (7)	0.7849 (7)	0.5000	0.129 (5)
H1A	0.7940	0.7143	0.5084	0.155*	0.5
H1B	0.7143	0.7940	0.4916	0.155*	0.5
Cl2	0.5832 (2)	0.4681 (3)	0.29535 (14)	0.1914 (18)
C2	0.5070 (6)	0.4930 (6)	0.2500	0.104 (4)
H2A	0.4366	0.4841	0.2589	0.125*	0.5
H2B	0.5159	0.5634	0.2411	0.125*	0.5

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0577 (10)	0.0520 (9)	0.0532 (10)	−0.0112 (8)	−0.0024 (8)	0.0031 (8)
O1	0.080 (3)	0.058 (3)	0.079 (3)	−0.008 (2)	0.002 (3)	−0.013 (3)
O2	0.048 (2)	0.081 (3)	0.069 (3)	−0.010 (2)	−0.014 (2)	0.010 (3)
O3	0.055 (3)	0.057 (3)	0.051 (3)	0.004 (2)	0.002 (2)	−0.014 (2)
O4	0.085 (3)	0.098 (4)	0.058 (3)	0.006 (3)	−0.026 (3)	0.001 (3)
O5	0.069 (3)	0.063 (3)	0.046 (3)	0.004 (2)	0.001 (2)	−0.013 (2)
O6	0.059 (3)	0.073 (3)	0.055 (3)	−0.017 (2)	0.008 (2)	−0.017 (2)
O7	0.053 (3)	0.075 (3)	0.071 (3)	−0.019 (2)	0.008 (2)	−0.004 (2)
N1	0.044 (3)	0.042 (3)	0.041 (3)	0.000 (2)	0.001 (2)	−0.006 (2)
N2	0.052 (3)	0.060 (3)	0.045 (3)	0.000 (3)	−0.009 (3)	−0.001 (3)
C3	0.046 (3)	0.049 (3)	0.042 (4)	−0.001 (3)	−0.002 (3)	−0.003 (3)
C4	0.045 (3)	0.046 (3)	0.041 (4)	−0.004 (3)	−0.002 (3)	0.000 (3)
C5	0.042 (3)	0.043 (3)	0.040 (4)	−0.005 (3)	0.002 (3)	0.000 (3)
C6	0.044 (3)	0.043 (3)	0.044 (4)	−0.005 (3)	0.006 (3)	0.001 (3)
C7	0.046 (3)	0.043 (3)	0.047 (4)	−0.004 (3)	0.004 (3)	0.000 (3)
C8	0.061 (4)	0.065 (4)	0.046 (4)	−0.011 (4)	−0.006 (3)	−0.001 (3)
C9	0.085 (5)	0.077 (5)	0.052 (4)	−0.013 (4)	0.001 (4)	−0.009 (4)
C10	0.046 (3)	0.052 (4)	0.069 (5)	−0.006 (3)	−0.014 (3)	0.001 (4)
C11	0.049 (4)	0.056 (4)	0.084 (5)	0.010 (3)	−0.005 (4)	−0.004 (4)
C12	0.056 (4)	0.054 (4)	0.067 (5)	0.008 (3)	0.001 (4)	−0.006 (3)
C13	0.045 (3)	0.046 (3)	0.045 (4)	−0.005 (3)	0.002 (3)	−0.003 (3)
C14	0.056 (4)	0.040 (3)	0.053 (4)	−0.009 (3)	0.006 (3)	−0.004 (3)
C15	0.040 (3)	0.052 (4)	0.044 (4)	0.002 (3)	0.005 (3)	0.004 (3)
C16	0.049 (4)	0.048 (3)	0.053 (4)	−0.004 (3)	0.008 (3)	−0.004 (3)
C17	0.048 (3)	0.043 (3)	0.049 (4)	−0.003 (3)	−0.002 (3)	−0.004 (3)
C18	0.054 (4)	0.072 (4)	0.062 (5)	−0.002 (3)	−0.001 (4)	−0.019 (4)
C19	0.104 (6)	0.129 (7)	0.071 (6)	−0.023 (5)	0.010 (5)	−0.036 (5)
C20	0.036 (3)	0.049 (3)	0.066 (5)	−0.005 (3)	0.001 (3)	0.004 (3)
C21	0.050 (4)	0.101 (6)	0.080 (6)	−0.016 (4)	0.012 (4)	0.001 (4)
C22	0.049 (4)	0.062 (4)	0.049 (4)	0.001 (3)	0.006 (3)	−0.004 (3)
C23	0.050 (4)	0.057 (4)	0.047 (4)	0.000 (3)	0.000 (3)	−0.008 (3)
C24	0.089 (6)	0.089 (5)	0.066 (5)	−0.020 (4)	0.005 (4)	0.029 (4)
Cl1	0.143 (2)	0.0998 (18)	0.176 (3)	0.0013 (17)	0.000 (2)	0.0064 (19)
C1	0.130 (8)	0.130 (8)	0.129 (13)	−0.038 (10)	−0.012 (8)	0.012 (8)
Cl2	0.141 (2)	0.201 (3)	0.233 (4)	−0.062 (2)	−0.057 (3)	0.117 (3)
C2	0.081 (5)	0.081 (5)	0.150 (13)	0.004 (7)	0.028 (6)	0.028 (6)

Geometric parameters (Å, º)

S1—O1	1.429 (5)	C11—C12	1.386 (9)
S1—O2	1.435 (4)	C12—H12	0.9300
S1—C3	1.767 (5)	C12—C13	1.381 (8)
S1—C24	1.748 (6)	C13—C14	1.477 (8)
O3—C5	1.220 (6)	C15—C16	1.393 (8)
O4—C8	1.217 (7)	C15—C23	1.376 (7)
O5—C14	1.213 (7)	C16—H16	0.9300
O6—C17	1.365 (7)	C16—C17	1.388 (7)
O6—C18	1.427 (7)	C17—C20	1.409 (8)
O7—C20	1.370 (6)	C18—H18A	0.9700
O7—C21	1.428 (7)	C18—H18B	0.9700
N1—C4	1.481 (7)	C18—C19	1.496 (8)
N1—C5	1.386 (6)	C19—H19A	0.9600
N1—C14	1.392 (7)	C19—H19B	0.9600
N2—H2	0.8597	C19—H19C	0.9600
N2—C7	1.398 (7)	C20—C22	1.379 (8)
N2—C8	1.374 (8)	C21—H21A	0.9600
C3—H3A	0.9700	C21—H21B	0.9600
C3—H3B	0.9700	C21—H21C	0.9600
C3—C4	1.529 (7)	C22—H22	0.9300
C4—H4	0.9800	C22—C23	1.395 (8)
C4—C15	1.520 (8)	C23—H23	0.9300
C5—C6	1.478 (8)	C24—H24A	0.9600
C6—C7	1.379 (8)	C24—H24B	0.9600
C6—C13	1.380 (7)	C24—H24C	0.9600
C7—C10	1.402 (8)	Cl1—C1	1.726 (8)
C8—C9	1.484 (9)	C1—Cl1^i	1.726 (8)
C9—H9A	0.9600	C1—H1A	0.9700
C9—H9B	0.9600	C1—H1B	0.9700
C9—H9C	0.9600	Cl2—C2	1.706 (7)
C10—H10	0.9300	C2—Cl2^ii	1.706 (7)
C10—C11	1.371 (9)	C2—H2A	0.9700
C11—H11	0.9300	C2—H2B	0.9700
O1—S1—O2	117.7 (3)	O5—C14—C13	128.9 (6)
O1—S1—C3	108.9 (3)	N1—C14—C13	107.1 (5)
O1—S1—C24	109.8 (3)	C16—C15—C4	122.7 (5)
O2—S1—C3	108.5 (3)	C23—C15—C4	118.4 (5)
O2—S1—C24	108.4 (3)	C23—C15—C16	119.0 (5)
C24—S1—C3	102.4 (3)	C15—C16—H16	119.2
C17—O6—C18	117.2 (4)	C17—C16—C15	121.5 (5)
C20—O7—C21	116.8 (5)	C17—C16—H16	119.2
C5—N1—C4	123.8 (5)	O6—C17—C16	125.5 (5)
C5—N1—C14	110.4 (5)	O6—C17—C20	115.5 (5)
C14—N1—C4	125.4 (5)	C16—C17—C20	118.9 (6)
C7—N2—H2	115.5	O6—C18—H18A	110.1
C8—N2—H2	115.1	O6—C18—H18B	110.1
C8—N2—C7	129.4 (6)	O6—C18—C19	108.0 (5)
S1—C3—H3A	108.8	H18A—C18—H18B	108.4
S1—C3—H3B	108.8	C19—C18—H18A	110.1
H3A—C3—H3B	107.7	C19—C18—H18B	110.1
C4—C3—S1	113.9 (4)	C18—C19—H19A	109.5
C4—C3—H3A	108.8	C18—C19—H19B	109.5
C4—C3—H3B	108.8	C18—C19—H19C	109.5
N1—C4—C3	111.4 (4)	H19A—C19—H19B	109.5
N1—C4—H4	107.1	H19A—C19—H19C	109.5
N1—C4—C15	112.3 (4)	H19B—C19—H19C	109.5
C3—C4—H4	107.1	O7—C20—C17	115.5 (6)
C15—C4—C3	111.5 (5)	O7—C20—C22	125.0 (6)
C15—C4—H4	107.1	C22—C20—C17	119.4 (5)
O3—C5—N1	125.1 (5)	O7—C21—H21A	109.5
O3—C5—C6	127.9 (5)	O7—C21—H21B	109.5
N1—C5—C6	107.0 (5)	O7—C21—H21C	109.5
C7—C6—C5	130.9 (5)	H21A—C21—H21B	109.5
C7—C6—C13	121.1 (5)	H21A—C21—H21C	109.5
C13—C6—C5	107.9 (5)	H21B—C21—H21C	109.5
N2—C7—C10	124.8 (6)	C20—C22—H22	119.6
C6—C7—N2	118.0 (5)	C20—C22—C23	120.7 (6)
C6—C7—C10	117.2 (6)	C23—C22—H22	119.6
O4—C8—N2	122.7 (6)	C15—C23—C22	120.4 (6)
O4—C8—C9	122.2 (6)	C15—C23—H23	119.8
N2—C8—C9	115.1 (6)	C22—C23—H23	119.8
C8—C9—H9A	109.5	S1—C24—H24A	109.5
C8—C9—H9B	109.5	S1—C24—H24B	109.5
C8—C9—H9C	109.5	S1—C24—H24C	109.5
H9A—C9—H9B	109.5	H24A—C24—H24B	109.5
H9A—C9—H9C	109.5	H24A—C24—H24C	109.5
H9B—C9—H9C	109.5	H24B—C24—H24C	109.5
C7—C10—H10	119.8	Cl1—C1—Cl1^i	114.1 (8)
C11—C10—C7	120.3 (6)	Cl1^i—C1—H1A	108.7
C11—C10—H10	119.8	Cl1—C1—H1A	108.7
C10—C11—H11	118.5	Cl1—C1—H1B	108.7
C10—C11—C12	123.1 (6)	Cl1^i—C1—H1B	108.7
C12—C11—H11	118.5	H1A—C1—H1B	107.6
C11—C12—H12	122.1	Cl2^ii—C2—Cl2	112.9 (7)
C13—C12—C11	115.7 (6)	Cl2^ii—C2—H2A	109.0
C13—C12—H12	122.1	Cl2—C2—H2A	109.0
C6—C13—C12	122.5 (6)	Cl2^ii—C2—H2B	109.0
C6—C13—C14	107.6 (5)	Cl2—C2—H2B	109.0
C12—C13—C14	129.9 (6)	H2A—C2—H2B	107.8
O5—C14—N1	124.1 (6)
S1—C3—C4—N1	60.0 (5)	C7—N2—C8—O4	−4.8 (10)
S1—C3—C4—C15	−173.7 (4)	C7—N2—C8—C9	173.4 (5)
O1—S1—C3—C4	60.3 (5)	C7—C6—C13—C12	1.3 (9)
O2—S1—C3—C4	−69.0 (5)	C7—C6—C13—C14	−178.9 (5)
O3—C5—C6—C7	−2.0 (10)	C7—C10—C11—C12	1.5 (10)
O3—C5—C6—C13	178.8 (5)	C8—N2—C7—C6	−179.6 (6)
O6—C17—C20—O7	1.8 (8)	C8—N2—C7—C10	−0.2 (9)
O6—C17—C20—C22	−179.6 (5)	C10—C11—C12—C13	−1.3 (10)
O7—C20—C22—C23	178.1 (5)	C11—C12—C13—C6	−0.1 (9)
N1—C4—C15—C16	101.6 (6)	C11—C12—C13—C14	−179.7 (6)
N1—C4—C15—C23	−79.5 (6)	C12—C13—C14—O5	−0.5 (10)
N1—C5—C6—C7	178.1 (6)	C12—C13—C14—N1	−179.8 (6)
N1—C5—C6—C13	−1.2 (6)	C13—C6—C7—N2	178.2 (5)
N2—C7—C10—C11	−179.6 (5)	C13—C6—C7—C10	−1.2 (8)
C3—C4—C15—C16	−24.2 (8)	C14—N1—C4—C3	53.7 (7)
C3—C4—C15—C23	154.7 (5)	C14—N1—C4—C15	−72.2 (7)
C4—N1—C5—O3	−5.2 (8)	C14—N1—C5—O3	−178.5 (5)
C4—N1—C5—C6	174.8 (4)	C14—N1—C5—C6	1.5 (6)
C4—N1—C14—O5	6.2 (9)	C15—C16—C17—O6	−179.6 (5)
C4—N1—C14—C13	−174.4 (5)	C15—C16—C17—C20	0.9 (8)
C4—C15—C16—C17	177.6 (5)	C16—C15—C23—C22	0.8 (9)
C4—C15—C23—C22	−178.1 (5)	C16—C17—C20—O7	−178.7 (5)
C5—N1—C4—C3	−118.6 (6)	C16—C17—C20—C22	−0.1 (8)
C5—N1—C4—C15	115.5 (5)	C17—O6—C18—C19	178.2 (6)
C5—N1—C14—O5	179.4 (5)	C17—C20—C22—C23	−0.3 (9)
C5—N1—C14—C13	−1.3 (6)	C18—O6—C17—C16	0.3 (8)
C5—C6—C7—N2	−0.9 (9)	C18—O6—C17—C20	179.8 (5)
C5—C6—C7—C10	179.7 (5)	C20—C22—C23—C15	0.0 (9)
C5—C6—C13—C12	−179.4 (5)	C21—O7—C20—C17	−178.0 (5)
C5—C6—C13—C14	0.4 (6)	C21—O7—C20—C22	3.5 (9)
C6—C7—C10—C11	−0.2 (8)	C23—C15—C16—C17	−1.3 (9)
C6—C13—C14—O5	179.8 (6)	C24—S1—C3—C4	176.5 (4)
C6—C13—C14—N1	0.5 (6)

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

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O3	0.86	2.29	2.970 (6)	136
C3—H3A···O5^i	0.97	2.29	3.155 (7)	147
C3—H3A···O5	0.97	2.47	3.080 (7)	121
C3—H3B···O4^iii	0.97	2.62	3.581 (8)	170
C10—H10···O4	0.93	2.31	2.904 (8)	121
C16—H16···O5^i	0.93	2.42	3.345 (7)	179
C22—H22···O1^iii	0.93	2.52	3.432 (8)	169
C24—H24A···O2^i	0.96	2.53	3.429 (9)	156
C24—H24C···O3^iv	0.96	2.44	3.103 (7)	126

Symmetry codes: (i) y, x, −z+1; (iii) x+1/2, −y+1/2, −z+3/4; (iv) −y+1/2, x−1/2, z+1/4.