(+)-(3S,4R)-Norcisapride hydrogen (2R,3R)-tartrate monohydrate

The title compound, (+)-(3S,4R)-cis-4-amino-5-chloro-2-meth­oxy-N-(3-methoxy­piperidin-1-ium-4-yl)­benz­amidehydrogen (2R,3R)-di­hydroxy­butane­dioate monohydrate, C₁₄H₂₁ClN₃O₃⁺·C₄H₅O₆⁻·H₂O, is the (+)-tartrate salt of (+)-norcisapride. It has been found that (+)-norcisapride has both 5-HT3 antagonistic and 5-HT4 agonistic properties and is further substantially devoid of central nervous system effects. An intramolecular N—H...O hydrogen bond forces the amido group to be roughly coplanar with the substituted benzene ring. A three-dimensional network of hydrogen bonds is formed in the crystal. The absolute configuration of (+)-norcisapride is 3S,4R.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.004 Å
• R factor = 0.037
• wR factor = 0.107
• Data-to-parameter ratio = 8.0

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry


 Alert Level C:



ABSTM_02  Alert C The ratio of expected to reported Tmax/Tmin(RR') is < 0.90
          Tmin and Tmax reported:      0.325     0.593
          Tmin' and Tmax expected:      0.373     0.593
          RR' =      0.872
          Please check that your absorption correction is appropriate.

General Notes



REFLT_03
         From the CIF: _diffrn_reflns_theta_max           69.02
         From the CIF: _reflns_number_total               2350
         Count of symmetry unique reflns         2234
         Completeness (_total/calc)            105.19%
         TEST3: Check Friedels for noncentro structure
         Estimate of Friedel pairs measured       116
         Fraction of Friedel pairs measured     0.052
         Are heavy atom types Z>Si present          yes
          WARNING: Large fraction of Friedel related reflns may
                   be needed to determine absolute structure


 0 Alert Level A = Potentially serious problem

 0 Alert Level B = Potential problem

 1 Alert Level C = Please check

---

S1. Comment

The title compound, (I), is the (+)-tartrate salt of the (+)-enantiomer of norcisapride.

Racemic norcisapride is the principal metabolite of racemic cisapride, a widely used gastrokinetic drug (Meuldermans et al., 1988). The metabolization occurs mainly via the cytochrome P-450 isoenzyme CYP3A4 (Bohets et al., 2000). Certain therapeutic agents (e.g. ketoconazole) that inhibit the metabolic pathway of cisapride can give rise to undesirably high cisapride blood levels that may cause side effects.

It has been discovered that (-)-norcisapride is a potent drug for the treatment of gastro-esophageal reflux disease while substantially reducing adverse effects associated with the administration of racemic cisapride (McCullough & Aberg, 1998). It has also been found that (+)-norcisapride has both 5-HT3 antagonistic and 5-HT4 agonistic properties and is further substantially devoid of central nervous system effects (Heykants et al., 1999).

To contribute to a better understanding of the mechanism of action of the (-)- and (+)-norcisapride, the crystal structure and absolute configuration of the title compound was determined.

The absolute configuration of the (+)-norcisapride moiety is 3S,4R in view of the fact that the Flack (1983) parameter for this configuration is −0.01 (2) and that the known configuration 2R,3R for (+)-tartrate is obtained. As in the structures of cisapride (Collin et al., 1989) and cisapride tartrate (Peeters et al., 1997) an intramolecular hydrogen bond between the amidic N atom and the O atom of the o-methoxy substituent (Table 1) forces the amido moiety and the substituted benzene ring to be roughly coplanar [dihedral angle between the two least-squares planes: 10.8 (1)°]. The C atom chain of the hydrogen tartrate ion is in an extended conformation with the hydroxyl O atoms -sc with respect to one another. The hydrogen bonds listed in Table 2 form a three-dimensional network in the crystal.

S2. Experimental

The title compound was obtained from the Janssen Rechearch Foundation, Beerse, Belgium. The synthesis has been described by Heykants et al. (1999). Single crystals were grown by slow evaporation from a solution in methanol–water.

S3. Refinement

The positions of the H atoms of the water molecule were obtained with the program HYDROGEN (Nardelli, 1999). Those of the OH and methyl groups were found from a circular difference Fourier synthesis. The remaining H atoms were calculated geometrically. All H atoms were included in the refinement, but constrained to ride on their parent atoms. The isotropic displacement parameters of the H atoms were fixed at 1.25U_eq of their parent atoms.

Computing details

Data collection: XSCANS (Siemens, 1996); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: DIAMOND (Bergerhoff, 1996); software used to prepare material for publication: PARST (Nardelli, 1983), PLATON (Spek, 1998) and WinGX (Farrugia, 1999).

Figures

Fig. 1. Perspective view of the title compound with the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.

(+)-(3S,4R)-cis-4-amino-5-chloro-2-methoxy-N-(3-methoxypiperidin-1-ium-4-yl) benzamide hydrogen (2R,3R)-dihydroxybutanedioate monohydrate

Crystal data

C14H21ClN3O3^+·C4H5O6^−·H2O	F(000) = 508
Mr = 481.89	Dx = 1.407 Mg m^−3
Monoclinic, P21	Cu Kα radiation, λ = 1.54178 Å
a = 7.6086 (4) Å	Cell parameters from 39 reflections
b = 10.664 (1) Å	θ = 10.8–28.0°
c = 14.0482 (6) Å	µ = 2.01 mm^−1
β = 93.980 (6)°	T = 293 K
V = 1137.1 (1) Å^3	Block, colourless
Z = 2	0.45 × 0.30 × 0.26 mm

Data collection

Siemens P4 four-circle diffractometer	Rint = 0.033
ω/2θ scans	θmax = 69.0°
Absorption correction: ψ scan (XEMP; Siemens, 1989)	h = −1→8
Tmin = 0.325, Tmax = 0.593	k = −1→12
2935 measured reflections	l = −17→17
2350 independent reflections	3 standard reflections every 100 reflections
2280 reflections with F^2 > 2σ(F^2)	intensity decay: none

Refinement

Refinement on F^2	w = 1/[σ^2(Fo^2) + (0.069P)^2 + 0.2043P] where P = (Fo^2 + 2Fc^2)/3
Least-squares matrix: full	(Δ/σ)max < 0.001
R[F^2 > 2σ(F^2)] = 0.037	Δρmax = 0.21 e Å^−3
wR(F^2) = 0.107	Δρmin = −0.26 e Å^−3
S = 1.06	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin((2θ)]^-1/4
2350 reflections	Extinction coefficient: 0.026 (2)
295 parameters	Absolute structure: Flack (1983), 220 Friedel pairs
H-atom parameters constrained	Absolute structure parameter: −0.01 (2)

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

	x	y	z	Uiso*/Ueq
N1	1.0233 (3)	0.8441 (3)	0.5720 (2)	0.0472 (8)*
C2	0.9115 (5)	0.9582 (4)	0.5754 (2)	0.052 (1)*
C3	0.8016 (4)	0.9525 (3)	0.6611 (2)	0.0445 (8)*
C4	0.6873 (4)	0.8348 (3)	0.6578 (2)	0.0443 (8)*
C5	0.7988 (4)	0.7178 (3)	0.6499 (2)	0.0472 (9)*
C6	0.9171 (4)	0.7267 (4)	0.5667 (2)	0.051 (1)*
O7	0.9111 (3)	0.9443 (2)	0.7472 (1)	0.0496 (6)*
C8	0.9896 (8)	1.0584 (5)	0.7775 (4)	0.094 (2)*
N9	0.5907 (3)	0.8322 (3)	0.7439 (2)	0.0509 (9)*
C10	0.4270 (4)	0.7920 (3)	0.7488 (2)	0.043 (1)*
O11	0.3413 (3)	0.7443 (2)	0.6784 (1)	0.0489 (6)*
C12	0.3447 (3)	0.8048 (3)	0.8414 (2)	0.0416 (9)*
C13	0.4104 (4)	0.8751 (3)	0.9209 (2)	0.0468 (9)*
C14	0.3177 (4)	0.8832 (4)	1.0018 (2)	0.0506 (9)*
C15	0.1554 (4)	0.8235 (3)	1.0080 (2)	0.0494 (9)*
C16	0.0901 (4)	0.7531 (3)	0.9287 (2)	0.0469 (9)*
C17	0.1846 (4)	0.7434 (3)	0.8483 (2)	0.0430 (8)*
O18	0.5680 (3)	0.9344 (3)	0.9141 (2)	0.0615 (8)*
C19	0.6417 (6)	1.0067 (6)	0.9924 (3)	0.083 (2)*
N20	0.0663 (5)	0.8328 (4)	1.0882 (2)	0.071 (1)*
Cl21	−0.1091 (1)	0.6751 (1)	0.93367 (7)	0.0695 (3)*
O22	0.7777 (4)	0.3019 (4)	0.5790 (2)	0.076 (1)*
O23	0.8168 (3)	0.4087 (3)	0.7152 (2)	0.0561 (8)*
C24	0.7273 (4)	0.3465 (4)	0.6541 (2)	0.0474 (9)*
C25	0.5358 (4)	0.3187 (3)	0.6734 (2)	0.0467 (9)*
O26	0.4549 (3)	0.2500 (3)	0.5963 (2)	0.0650 (9)*
C27	0.4360 (4)	0.4391 (3)	0.6895 (2)	0.0434 (9)*
O28	0.4358 (3)	0.5134 (2)	0.6063 (2)	0.0475 (7)*
C29	0.2509 (4)	0.4065 (3)	0.7192 (2)	0.047 (1)*
O30	0.1244 (3)	0.4570 (3)	0.6666 (2)	0.0628 (8)*
O31	0.2339 (3)	0.3397 (4)	0.7876 (2)	0.081 (1)*
O32	0.3290 (5)	0.0093 (4)	0.5658 (3)	0.109 (2)*
H1A	1.0982	0.8417	0.6244	0.059*
H1B	1.0877	0.8485	0.5207	0.059*
H2A	0.8349	0.9639	0.5174	0.065*
H2B	0.9857	1.0322	0.5795	0.065*
H3	0.7268	1.0272	0.6625	0.056*
H4	0.6027	0.8395	0.6020	0.055*
H5A	0.7224	0.6454	0.6411	0.059*
H5B	0.8714	0.7062	0.7088	0.059*
H6A	0.9954	0.6549	0.5678	0.064*
H6B	0.8449	0.7249	0.5070	0.064*
H8A	1.0636	1.0446	0.8347	0.117*
H8B	0.8994	1.1179	0.7901	0.117*
H8C	1.0592	1.0904	0.7286	0.117*
H9	0.6446	0.8589	0.7958	0.064*
H14	0.3645	0.9297	1.0536	0.063*
H17	0.1398	0.6945	0.7974	0.054*
H19A	0.7553	1.0375	0.9779	0.104*
H19B	0.6540	0.9551	1.0485	0.104*
H19C	0.5655	1.0761	1.0036	0.104*
H20A	0.1097	0.8759	1.1359	0.089*
H20B	−0.0334	0.7957	1.0912	0.089*
H25	0.5348	0.2672	0.7312	0.058*
H26	0.5276	0.2355	0.5572	0.081*
H27	0.4983	0.4851	0.7420	0.054*
H28	0.4080	0.5855	0.6188	0.059*
H30	0.0299	0.4393	0.6880	0.078*
H32A	0.3552	0.0810	0.5891	0.137*
H32B	0.3534	0.0097	0.5077	0.137*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.035 (1)	0.068 (2)	0.040 (1)	−0.003 (1)	0.0108 (9)	0.001 (1)
C2	0.052 (2)	0.061 (2)	0.045 (2)	−0.001 (2)	0.009 (1)	0.009 (1)
C3	0.040 (2)	0.053 (2)	0.041 (1)	0.004 (1)	0.007 (1)	0.001 (1)
C4	0.031 (1)	0.068 (2)	0.035 (1)	−0.002 (1)	0.0071 (9)	−0.005 (1)
C5	0.044 (2)	0.054 (2)	0.045 (1)	−0.007 (1)	0.009 (1)	−0.005 (1)
C6	0.044 (2)	0.062 (2)	0.049 (2)	−0.002 (1)	0.014 (1)	−0.011 (1)
O7	0.049 (1)	0.056 (1)	0.043 (1)	−0.005 (1)	−0.0005 (8)	−0.005 (1)
C8	0.123 (4)	0.068 (3)	0.087 (3)	−0.026 (3)	−0.023 (3)	−0.016 (2)
N9	0.029 (1)	0.090 (2)	0.035 (1)	−0.006 (1)	0.0060 (8)	−0.010 (1)
C10	0.037 (2)	0.055 (2)	0.038 (1)	0.003 (1)	0.005 (1)	−0.004 (1)
O11	0.041 (1)	0.064 (1)	0.041 (1)	−0.003 (1)	0.0038 (7)	−0.010 (1)
C12	0.030 (1)	0.055 (2)	0.040 (1)	0.002 (1)	0.007 (1)	−0.003 (1)
C13	0.043 (2)	0.056 (2)	0.042 (1)	−0.002 (1)	0.007 (1)	−0.008 (1)
C14	0.048 (2)	0.063 (2)	0.042 (1)	−0.001 (2)	0.008 (1)	−0.008 (1)
C15	0.051 (2)	0.058 (2)	0.041 (1)	0.008 (1)	0.017 (1)	0.005 (1)
C16	0.035 (2)	0.059 (2)	0.047 (1)	0.003 (1)	0.011 (1)	0.008 (1)
C17	0.035 (2)	0.053 (2)	0.041 (1)	0.002 (1)	0.003 (1)	0.001 (1)
O18	0.048 (1)	0.087 (2)	0.050 (1)	−0.022 (1)	0.0130 (9)	−0.024 (1)
C19	0.074 (3)	0.110 (4)	0.066 (2)	−0.031 (3)	0.008 (2)	−0.035 (3)
N20	0.072 (2)	0.093 (2)	0.052 (1)	−0.006 (2)	0.032 (1)	−0.002 (2)
Cl21	0.0483 (5)	0.0927 (7)	0.0693 (5)	−0.0162 (4)	0.0172 (3)	0.0086 (5)
O22	0.057 (2)	0.111 (2)	0.064 (1)	−0.009 (2)	0.032 (1)	−0.015 (2)
O23	0.029 (1)	0.083 (2)	0.056 (1)	−0.003 (1)	0.0063 (8)	0.001 (1)
C24	0.030 (1)	0.065 (2)	0.047 (1)	0.003 (1)	0.011 (1)	0.006 (1)
C25	0.035 (2)	0.056 (2)	0.049 (2)	−0.004 (1)	0.008 (1)	0.001 (1)
O26	0.048 (1)	0.069 (2)	0.078 (2)	−0.007 (1)	0.004 (1)	−0.020 (1)
C27	0.031 (2)	0.061 (2)	0.039 (1)	−0.006 (1)	0.009 (1)	−0.005 (1)
O28	0.037 (1)	0.054 (1)	0.053 (1)	−0.0037 (9)	0.0135 (8)	−0.001 (1)
C29	0.028 (1)	0.072 (2)	0.043 (1)	−0.001 (1)	0.009 (1)	−0.001 (1)
O30	0.026 (1)	0.098 (2)	0.065 (1)	−0.002 (1)	0.0074 (9)	0.021 (1)
O31	0.042 (1)	0.136 (3)	0.067 (1)	0.005 (2)	0.019 (1)	0.039 (2)
O32	0.105 (3)	0.072 (2)	0.149 (3)	−0.017 (2)	0.000 (2)	0.003 (3)

Geometric parameters (Å, º)

N1—H1A	0.900	C14—H14	0.930
N1—H1B	0.900	C14—C15	1.398 (5)
N1—C2	1.487 (5)	C15—C16	1.404 (4)
N1—C6	1.489 (5)	C15—N20	1.358 (5)
C2—H2A	0.970	C16—C17	1.384 (4)
C2—H2B	0.970	C16—Cl21	1.735 (3)
C2—C3	1.513 (4)	C17—H17	0.930
C3—H3	0.980	O18—C19	1.427 (5)
C3—C4	1.526 (5)	C19—H19A	0.960
C3—O7	1.423 (3)	C19—H19B	0.960
C4—H4	0.980	C19—H19C	0.960
C4—C5	1.517 (5)	N20—H20A	0.860
C4—N9	1.459 (4)	N20—H20B	0.860
C5—H5A	0.970	O22—C24	1.242 (4)
C5—H5B	0.970	O23—C24	1.249 (4)
C5—C6	1.527 (5)	C24—C25	1.529 (4)
C6—H6A	0.970	C25—H25	0.980
C6—H6B	0.970	C25—O26	1.413 (4)
O7—C8	1.408 (6)	C25—C27	1.517 (5)
C8—H8A	0.960	O26—H26	0.820
C8—H8B	0.960	C27—H27	0.980
C8—H8C	0.960	C27—O28	1.412 (4)
N9—H9	0.860	C27—C29	1.536 (4)
N9—C10	1.323 (4)	O28—H28	0.820
C10—O11	1.254 (3)	C29—O30	1.290 (4)
C10—C12	1.488 (4)	C29—O31	1.210 (5)
C12—C13	1.408 (4)	O30—H30	0.820
C12—C17	1.392 (4)	O32—H32A	0.850
C13—C14	1.382 (4)	O32—H32B	0.850
C13—O18	1.364 (4)
H1A—N1—H1B	107.9	C10—C12—C17	116.2 (2)
H1A—N1—C2	109.1	C13—C12—C17	117.3 (3)
H1A—N1—C6	109.1	C12—C13—C14	120.9 (3)
H1B—N1—C2	109.1	C12—C13—O18	117.2 (3)
H1B—N1—C6	109.1	C14—C13—O18	122.0 (3)
C2—N1—C6	112.3 (3)	C13—C14—H14	119.1
N1—C2—H2A	109.7	C13—C14—C15	121.7 (3)
N1—C2—H2B	109.7	H14—C14—C15	119.1
N1—C2—C3	110.0 (3)	C14—C15—C16	117.4 (3)
H2A—C2—H2B	108.2	C14—C15—N20	120.8 (3)
H2A—C2—C3	109.7	C16—C15—N20	121.9 (3)
H2B—C2—C3	109.7	C15—C16—C17	120.8 (3)
C2—C3—H3	109.8	C15—C16—Cl21	119.1 (2)
C2—C3—C4	110.8 (3)	C17—C16—Cl21	120.1 (2)
C2—C3—O7	110.8 (2)	C12—C17—C16	121.9 (3)
H3—C3—C4	109.8	C12—C17—H17	119.1
H3—C3—O7	109.8	C16—C17—H17	119.0
C4—C3—O7	105.9 (2)	C13—O18—C19	119.8 (3)
C3—C4—H4	108.9	O18—C19—H19A	109.5
C3—C4—C5	111.0 (3)	O18—C19—H19B	109.5
C3—C4—N9	108.0 (2)	O18—C19—H19C	109.5
H4—C4—C5	108.9	H19A—C19—H19B	109.5
H4—C4—N9	108.9	H19A—C19—H19C	109.5
C5—C4—N9	111.2 (2)	H19B—C19—H19C	109.5
C4—C5—H5A	109.3	C15—N20—H20A	120.0
C4—C5—H5B	109.3	C15—N20—H20B	120.0
C4—C5—C6	111.5 (3)	H20A—N20—H20B	120.0
H5A—C5—H5B	108.0	O22—C24—O23	127.0 (3)
H5A—C5—C6	109.3	O22—C24—C25	115.5 (3)
H5B—C5—C6	109.3	O23—C24—C25	117.5 (3)
N1—C6—C5	111.1 (3)	C24—C25—H25	108.5
N1—C6—H6A	109.4	C24—C25—O26	109.5 (2)
N1—C6—H6B	109.4	C24—C25—C27	110.8 (2)
C5—C6—H6A	109.4	H25—C25—O26	108.5
C5—C6—H6B	109.4	H25—C25—C27	108.5
H6A—C6—H6B	108.0	O26—C25—C27	110.9 (3)
C3—O7—C8	114.6 (3)	C25—O26—H26	109.5
O7—C8—H8A	109.5	C25—C27—H27	108.3
O7—C8—H8B	109.5	C25—C27—O28	108.9 (3)
O7—C8—H8C	109.5	C25—C27—C29	109.1 (2)
H8A—C8—H8B	109.5	H27—C27—O28	108.3
H8A—C8—H8C	109.5	H27—C27—C29	108.3
H8B—C8—H8C	109.5	O28—C27—C29	113.8 (2)
C4—N9—H9	117.3	C27—O28—H28	109.5
C4—N9—C10	125.4 (2)	C27—C29—O30	114.3 (2)
H9—N9—C10	117.3	C27—C29—O31	120.0 (3)
N9—C10—O11	122.0 (3)	O30—C29—O31	125.7 (3)
N9—C10—C12	118.0 (2)	C29—O30—H30	109.5
O11—C10—C12	120.0 (2)	H32A—O32—H32B	107.7
C10—C12—C13	126.5 (2)
H1A—N1—C2—H2A	176.9	H9—N9—C10—O11	−175.6
H1A—N1—C2—H2B	58.2	H9—N9—C10—C12	4.4
H1A—N1—C2—C3	−62.5	N9—C10—C12—C13	12.0 (4)
H1B—N1—C2—H2A	59.2	N9—C10—C12—C17	−169.8 (3)
H1B—N1—C2—H2B	−59.4	O11—C10—C12—C13	−168.0 (3)
H1B—N1—C2—C3	179.9	O11—C10—C12—C17	10.2 (4)
C6—N1—C2—H2A	−62.0	C10—C12—C13—C14	177.6 (3)
C6—N1—C2—H2B	179.4	C10—C12—C13—O18	−2.3 (4)
C6—N1—C2—C3	58.7 (3)	C17—C12—C13—C14	−0.6 (4)
H1A—N1—C6—C5	64.9	C17—C12—C13—O18	179.5 (3)
H1A—N1—C6—H6A	−56.0	C10—C12—C17—C16	−176.6 (3)
H1A—N1—C6—H6B	−174.1	C10—C12—C17—H17	3.3
H1B—N1—C6—C5	−177.4	C13—C12—C17—C16	1.7 (4)
H1B—N1—C6—H6A	61.7	C13—C12—C17—H17	−178.3
H1B—N1—C6—H6B	−56.5	C12—C13—C14—H14	179.4
C2—N1—C6—C5	−56.3 (3)	C12—C13—C14—C15	−0.6 (5)
C2—N1—C6—H6A	−177.2	O18—C13—C14—H14	−0.7
C2—N1—C6—H6B	64.7	O18—C13—C14—C15	179.3 (3)
N1—C2—C3—H3	−179.1	C12—C13—O18—C19	−179.8 (3)
N1—C2—C3—C4	−57.7 (3)	C14—C13—O18—C19	0.3 (5)
N1—C2—C3—O7	59.5 (3)	C13—C14—C15—C16	0.7 (5)
H2A—C2—C3—H3	−58.5	C13—C14—C15—N20	−179.9 (3)
H2A—C2—C3—C4	62.9	H14—C14—C15—C16	−179.3
H2A—C2—C3—O7	−179.9	H14—C14—C15—N20	0.1
H2B—C2—C3—H3	60.2	C14—C15—C16—C17	0.4 (5)
H2B—C2—C3—C4	−178.4	C14—C15—C16—Cl21	178.9 (3)
H2B—C2—C3—O7	−61.2	N20—C15—C16—C17	−179.0 (3)
C2—C3—C4—H4	−64.3	N20—C15—C16—Cl21	−0.5 (4)
C2—C3—C4—C5	55.5 (3)	C14—C15—N20—H20A	0.0
C2—C3—C4—N9	177.6 (3)	C14—C15—N20—H20B	180.0
H3—C3—C4—H4	57.1	C16—C15—N20—H20A	179.4
H3—C3—C4—C5	176.9	C16—C15—N20—H20B	−0.6
H3—C3—C4—N9	−61.0	C15—C16—C17—C12	−1.6 (5)
O7—C3—C4—H4	175.5	C15—C16—C17—H17	178.4
O7—C3—C4—C5	−64.7 (3)	Cl21—C16—C17—C12	179.9 (2)
O7—C3—C4—N9	57.4 (3)	Cl21—C16—C17—H17	−0.2
C2—C3—O7—C8	77.3 (4)	C13—O18—C19—H19A	176.4
H3—C3—O7—C8	−44.1	C13—O18—C19—H19B	56.4
C4—C3—O7—C8	−162.6 (3)	C13—O18—C19—H19C	−63.6
C3—C4—C5—H5A	−173.9	O22—C24—C25—H25	115.9
C3—C4—C5—H5B	68.1	O22—C24—C25—O26	−2.4 (4)
C3—C4—C5—C6	−52.9 (3)	O22—C24—C25—C27	−125.1 (3)
H4—C4—C5—H5A	−54.1	O23—C24—C25—H25	−62.9
H4—C4—C5—H5B	−172.1	O23—C24—C25—O26	178.8 (3)
H4—C4—C5—C6	66.9	O23—C24—C25—C27	56.1 (4)
N9—C4—C5—H5A	65.8	C24—C25—O26—H26	2.6
N9—C4—C5—H5B	−52.1	H25—C25—O26—H26	−115.7
N9—C4—C5—C6	−173.1 (3)	C27—C25—O26—H26	125.3
C3—C4—N9—H9	−36.7	C24—C25—C27—H27	−56.2
C3—C4—N9—C10	143.3 (3)	C24—C25—C27—O28	61.4 (3)
H4—C4—N9—H9	−154.7	C24—C25—C27—C29	−173.9 (3)
H4—C4—N9—C10	25.3	H25—C25—C27—H27	62.8
C5—C4—N9—H9	85.3	H25—C25—C27—O28	−179.6
C5—C4—N9—C10	−94.7 (3)	H25—C25—C27—C29	−54.9
C4—C5—C6—N1	53.0 (3)	O26—C25—C27—H27	−178.1
C4—C5—C6—H6A	173.9	O26—C25—C27—O28	−60.5 (3)
C4—C5—C6—H6B	−67.9	O26—C25—C27—C29	64.2 (3)
H5A—C5—C6—N1	174.0	C25—C27—O28—H28	−164.0
H5A—C5—C6—H6A	−65.1	H27—C27—O28—H28	−46.4
H5A—C5—C6—H6B	53.1	C29—C27—O28—H28	74.2
H5B—C5—C6—N1	−68.0	C25—C27—C29—O30	−125.1 (3)
H5B—C5—C6—H6A	52.9	C25—C27—C29—O31	55.8 (4)
H5B—C5—C6—H6B	171.0	H27—C27—C29—O30	117.2
C3—O7—C8—H8A	−178.4	H27—C27—C29—O31	−61.9
C3—O7—C8—H8B	61.6	O28—C27—C29—O30	−3.3 (4)
C3—O7—C8—H8C	−58.4	O28—C27—C29—O31	177.6 (3)
C4—N9—C10—O11	4.3 (5)	C27—C29—O30—H30	−176.7
C4—N9—C10—C12	−175.6 (3)	O31—C29—O30—H30	2.3

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N9—H9···O18	0.86	1.97	2.643 (3)	134
O26—H26···O22	0.82	2.03	2.545 (4)	120
O28—H28···O11	0.82	1.97	2.776 (3)	167
O32—H32A···O26	0.85	1.96	2.764 (5)	158
N1—H1A···O11^i	0.90	2.21	2.953 (3)	140
N1—H1B···O22^ii	0.90	1.86	2.728 (4)	161
N20—H20A···O23^iii	0.86	2.16	2.955 (4)	155
N20—H20B···O31^iv	0.86	2.41	2.970 (4)	123
O30—H30···O23^v	0.82	1.72	2.535 (3)	171
O32—H32B···O28^vi	0.85	2.34	3.107 (5)	150

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