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Synthesis and X-ray structural investigations have been carried out for the two title compounds, viz. C20H30N2O3S, (I), and C18H28N2O3S, (II). In both mol­ecules, the cyclo­hexyl­oxy moiety and the conjugated cyclic system are located on opposite sides of the tetra­hydro­furan-2-one ring. In the crystal structure of (II), there are two types of inter­molecular hydrogen bonds, viz. C—H...S and N—H...O, and the mol­ecules form a three-dimensional supramolecular architecture via the hydrogen bonds.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270105007833/av1224sup1.cif
Contains datablocks global, I, II

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270105007833/av1224Isup2.hkl
Contains datablock I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270105007833/av1224IIsup3.hkl
Contains datablocks II, II, II

CCDC references: 275535; 275536

Comment top

The chemistry and biology of nucleoside analogues have been the subject of intensive study, since they possess many potent bioactivities, such as antiviral properties, for example against herpes simplex, AIDS-driven viral infections and the human immunodeficiency virus (Guillarme et al., 2003; Perbost et al., 1992; Wang et al., 2001; Remco et al., 2000). As part of our research work on nucleoside analogues, we synthesized the title compounds, (I) and (II), from 5-(R)-menthyloxy-2(5H)-furanone, (III), in order to evaluate their biological activity, and we report their structures here.

Compounds (I) and (II) are both composed of three sections, namely a cyclohexyloxy moiety, a tetrahydrofuran-2-one ring and a conjugated cyclic system, of which the first two almost have the same configuration in the two compounds, with similar bond distances and bond angles. Compounds (I) and (II) are not flat molecules (Figs. 1 and 2). The cyclohexyloxy section and the conjugated cyclic system are located on opposite sides of the tetrahydrofuran-2-one ring and the three rings are not coplanar with each other. In the cyclohexyloxy section, the six-membered ring adopts a chair conformation, with the isopropyl and methyl groups both located in the β-position, which is beneficial to the stability of the structure.

In the 4,6-dimethylpyrimidin-2-ylsulfanyl section of compound (I), all the non-H atoms of the group are coplanar, with a mean deviation of 0.013 (2) Å. The electrons of the ring are highly delocalized, with similar C—N and C—C bond distances (Table 1). The C15—S1 bond distance, which is shorter than C3—S1, arises from the conjugation of the electrons of atom S1 with the pyrimidinyl ring.

In the 4-methyl-1,3-thiazol-2-ylamino section of compound (II), all the non-H atoms of the group are coplanar, with a mean deviation of 0.009 (2) Å. The electrons on the ring are not as delocalized as those in (I). There are two obviously different C—N bond distances, C15—N2 and C16—N2. The C16—C17 bond distance is 1.332 (3) Å, characterizing a CC double bond (Table 2). The short bond distances of C17—S1 and C15—S1 result from the conjugation of the electrons of atom S1 with atoms C15 and C17. The N1—C15 bond distance is shorter than the single bond C3—N1, but longer than that of the double bond C15—N2 [1.291 (3) Å], which can be attributed to the conjugation of the electrons of atom N1 with atoms C15 and N2.

Compound (II) contains one S atom, two N atoms and three O atoms, which are potential hydrogen-bond acceptors. One of the two N atoms (atom N1 of the NH group) is also a strong hydrogen-bond donor. However, the present results show that only two sites, one S atom (S1) and one O atom (O2), act as hydrogen-bond acceptors, and one N atom (N1) and one C atom (C10) act as hydrogen-bond donors, forming two types of intermolecular hydrogen bonds, C—H···S and N—H···O (Table 3). The C—H, H···S and C···S distances and the C—H···S angle indicate a weak hydrogen bond, while the N—H, H···O and N···O distances and the N—H···O angle indicate a strong hydrogen bond. Each molecule is connected to four adjacent ones through four intermolecular hydrogen bonds, two C—H···S hydrogen bonds and two N—H···O hydrogen bonds (Fig. 3). Through the action of these two types of hydrogen bonds, compound (II) forms a three-dimensional supramolecular architecture.

The crystal analysis shows the configuration of C3 is R in which compound?.

Experimental top

For the preparation of (I), triethylamine (404 mg, 4 mmol) was added at 298 K under nitrogen to a stirred mixture of 4,6-dimethylpyrimidine-2-thiol (280 mg, 2 mmol) and (III) (476 mg, 2 mmol) (Hui Huang et al., 1999) in dimethylformamide (8 ml). The mixture was stirred at room temperature. The completion of the reaction was monitored using thin-layer chromatography. CH2Cl2 was added to the mixture, which was then filtered. The filtrate was washed with H2O, dried, and condensed in vacuo to give the crude product. Column chromatography gave colourless crystals of (I) (417 mg, 55%; m.p. 415.8–416.2 K). Recrystallization from petroleum–AcOEt (Ratio?) yielded crystals of (I) suitable for X-ray analysis. For the preparation of (II), to a mixture of 2-amino-4-methylthiazolyl (484 mg, 2 mmol), K2CO3 (1.11 g, 8 mmol) and tetrabutylammoniumbromide (322 mg, 1 mmol) was added CH3CN (6 ml) and (III) (476 mg, 2 mmol). The reaction solution was stirred at room temperature for 2 d. AcOEt was added and the resulting mixture was washed with water and condensed in vacuo to provide the crude product, which was purified by flash chromatography, giving (II) as a light-yellow crystals (359 mg, 51%; m.p.466.5–468 K). Recrystallization from petroleum–AcOEt (Ratio?) yielded crystals of (II).

Refinement top

H atoms were generated goemetrically and allowed to ride on their parent C atoms, with C—H distances of 0.96 (CH3), 0.97 (CH2), 0.98 Å (CH) or 0.93 Å (unsaturated CH), and N—H distances of 0.86°, and with Uico(H) = 1.2Ueq(C,N). Please check added text. The absolute structure was set by reference to the known chirality of the cyclohexyloxy moiety.

Computing details top

For both compounds, data collection: SMART (Bruker, 1999); cell refinement: SMART; data reduction: SAINT (Bruker, 1999); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1997); software used to prepare material for publication: SHELXTL.

Figures top
[Figure 1] Fig. 1. The structure of (I), showing 30% probability displacement ellipsoids and the atom-numbering scheme.
[Figure 2] Fig. 2. The structure of (II), showing 30% probability displacement ellipsoids and the atom-numbering scheme.
[Figure 3] Fig. 3. A packing view for (II), showing the hydrogen bonding. Atoms labelled with the suffixes AE are at the symmetry positions (x, y, z) (1/2 + x, 1/2 − y, −z), (x − 1/2, 1/2 − y, −z), (−x, −1/2 + y, 1/2 − z) and (−x, y − 1/2, 1/2 − z), respectively.
(I) (4R,5R)-4-(4,6-dimethylpyrimidin-2-ylsulfanyl)-5-[(2S,5R)-2-isopropyl- 5-methylcyclohexyloxy]-2,3,4,5-tetrahydrofuran-2-one top
Crystal data top
C20H30N2O3SDx = 1.162 Mg m3
Mr = 378.52Melting point = 415.8–416.2 K
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 956 reflections
a = 8.825 (4) Åθ = 2.7–25.5°
b = 14.401 (6) ŵ = 0.17 mm1
c = 17.033 (7) ÅT = 293 K
V = 2164.5 (15) Å3Prism, colourless
Z = 40.42 × 0.32 × 0.26 mm
F(000) = 816
Data collection top
Bruker SMART CCD area-detector
diffractometer
4425 independent reflections
Radiation source: fine-focus sealed tube3686 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.029
ϕ and ω scansθmax = 26.5°, θmin = 2.4°
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)
h = 1110
Tmin = 0.977, Tmax = 0.996k = 1717
12564 measured reflectionsl = 2110
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.037 w = 1/[σ2(Fo2) + (0.0476P)2 + 0.2336P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.097(Δ/σ)max = 0.001
S = 1.06Δρmax = 0.15 e Å3
4425 reflectionsΔρmin = 0.15 e Å3
242 parametersExtinction correction: SHELXL97 (Sheldrick, 1997), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 restraintsExtinction coefficient: 0.033 (2)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack (1983), with how many Friedel pairs
Secondary atom site location: difference Fourier mapAbsolute structure parameter: 0.00 (7)
Crystal data top
C20H30N2O3SV = 2164.5 (15) Å3
Mr = 378.52Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 8.825 (4) ŵ = 0.17 mm1
b = 14.401 (6) ÅT = 293 K
c = 17.033 (7) Å0.42 × 0.32 × 0.26 mm
Data collection top
Bruker SMART CCD area-detector
diffractometer
4425 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)
3686 reflections with I > 2σ(I)
Tmin = 0.977, Tmax = 0.996Rint = 0.029
12564 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.037H-atom parameters constrained
wR(F2) = 0.097Δρmax = 0.15 e Å3
S = 1.06Δρmin = 0.15 e Å3
4425 reflectionsAbsolute structure: Flack (1983), with how many Friedel pairs
242 parametersAbsolute structure parameter: 0.00 (7)
0 restraints
Special details top

Experimental. 1H NMR (500 MHz, CDCl3, δ, p.p.m.): 0.81 (3H, d, J = 6.9 Hz, H12), 0.92 (3H, d, J = 7.1 Hz, H14), 0.94 (3H, d, J = 6.6 Hz, H15), 0.97 (2H, m, H10), 1.01 (1H, m, H13), 1.29 (2H, m, H9), 1.69 (2H, m, H7), 2.13 (2H, m, H8, H11), 2.44 (6H, s, H8', H7'), 2.62 (1H, dd, J = 18.4, 2.6 Hz, H3), 3.26 (1H, dd, J = 18.4 and 9.0 Hz, H3), 3.56 (1H, dt, J = 10.7 and 4.1 Hz, H6), 4.15 (1H, dd, J = 8.8 and 1.0 Hz, H4), 5.73 (1H, s, H5), 6.79 (1H, s, H5'); 13C NMR (135DEPT, 125 MHz, CDCl3, δ, p.p.m.): 15.6 (C15), 20.9 (C14), 22.2 (C12), 3.1 (C10), 23.8 (C7',8'), 25.5 (t, C13), 31.3 (C8), 33.6 (C9), 34.3 (C3), 40.2 (C7), 44.4 (C11), 47.8 (C4), 77.6 (C6), 104.6 (C5), 116.6 (C5'), 167.6 (C4',6'), 169.1 (C2'), 175.0 (C2); IR (KBr, cm−1): ν 1778(C=O).

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 (Å2) top
xyzUiso*/Ueq
S10.62843 (5)0.48529 (3)0.98734 (3)0.05309 (16)
N10.33120 (17)0.48972 (11)0.96069 (10)0.0516 (4)
N20.46554 (18)0.63351 (11)0.96853 (10)0.0533 (4)
O10.69087 (15)0.32620 (10)0.84871 (8)0.0520 (3)
O20.90826 (17)0.26210 (14)0.88812 (12)0.0808 (5)
O30.45180 (15)0.27066 (9)0.87819 (7)0.0470 (3)
C10.7869 (2)0.29372 (14)0.90440 (13)0.0527 (5)
C20.7177 (2)0.30465 (14)0.98371 (12)0.0525 (5)
H2A0.78770.33471.01950.063*
H2B0.68900.24481.00530.063*
C30.57801 (19)0.36530 (13)0.96988 (11)0.0426 (4)
H30.49300.34591.00310.051*
C40.54515 (19)0.34749 (13)0.88331 (11)0.0405 (4)
H40.49880.40190.85840.049*
C50.3968 (3)0.25032 (15)0.79984 (12)0.0563 (6)
H50.47580.26600.76160.068*
C60.3671 (4)0.14551 (19)0.79691 (13)0.0776 (8)
H60.28800.13260.83580.093*
C70.2994 (5)0.1228 (3)0.71627 (19)0.1120 (13)
H7A0.37520.13390.67610.134*
H7B0.27270.05750.71460.134*
C80.1606 (5)0.1802 (3)0.69856 (19)0.1225 (15)
H8A0.08140.16420.73570.147*
H8B0.12440.16470.64640.147*
C90.1900 (4)0.2841 (3)0.70275 (16)0.0994 (10)
H90.26520.29970.66250.119*
C100.2582 (3)0.3074 (2)0.78310 (13)0.0701 (7)
H10A0.28470.37270.78460.084*
H10B0.18320.29610.82360.084*
C110.5040 (5)0.08683 (19)0.81967 (18)0.0943 (10)
H110.54190.11120.86960.113*
C120.6343 (4)0.0926 (2)0.7608 (2)0.1152 (12)
H12A0.60490.06290.71270.173*
H12B0.72180.06200.78200.173*
H12C0.65790.15660.75070.173*
C130.4601 (6)0.0152 (2)0.8338 (2)0.1445 (18)
H13A0.38910.01870.87640.217*
H13B0.54920.05030.84660.217*
H13C0.41470.04010.78710.217*
C140.0495 (4)0.3430 (4)0.6878 (2)0.1458 (18)
H14A0.00960.32910.63670.219*
H14B0.07610.40760.69040.219*
H14C0.02560.32950.72690.219*
C150.4544 (2)0.54139 (13)0.97053 (11)0.0457 (4)
C160.2026 (2)0.53660 (16)0.94678 (14)0.0582 (5)
C170.2028 (2)0.63179 (17)0.94293 (15)0.0647 (6)
H170.11360.66410.93310.078*
C180.3372 (3)0.67880 (15)0.95390 (13)0.0595 (5)
C190.0622 (3)0.4795 (2)0.9355 (2)0.0914 (9)
H19A0.05450.46110.88150.137*
H19B0.02510.51560.94960.137*
H19C0.06730.42520.96810.137*
C200.3451 (4)0.78280 (18)0.9474 (2)0.0960 (9)
H20A0.44910.80230.94870.144*
H20B0.29140.81040.99060.144*
H20C0.29980.80220.89890.144*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0396 (2)0.0484 (3)0.0713 (3)0.0008 (2)0.0143 (2)0.0077 (2)
N10.0377 (8)0.0481 (9)0.0691 (11)0.0005 (7)0.0016 (7)0.0031 (8)
N20.0527 (10)0.0451 (9)0.0622 (11)0.0009 (8)0.0056 (8)0.0057 (8)
O10.0449 (7)0.0633 (9)0.0479 (8)0.0031 (7)0.0055 (6)0.0076 (6)
O20.0498 (9)0.0977 (14)0.0949 (13)0.0181 (9)0.0091 (9)0.0041 (10)
O30.0532 (8)0.0495 (7)0.0385 (7)0.0144 (6)0.0019 (6)0.0005 (6)
C10.0438 (11)0.0499 (11)0.0644 (14)0.0011 (9)0.0006 (10)0.0066 (10)
C20.0541 (11)0.0511 (11)0.0522 (11)0.0065 (9)0.0086 (10)0.0074 (9)
C30.0387 (9)0.0438 (9)0.0453 (10)0.0013 (7)0.0050 (8)0.0034 (8)
C40.0374 (9)0.0407 (10)0.0433 (10)0.0037 (8)0.0019 (8)0.0058 (8)
C50.0642 (14)0.0692 (14)0.0355 (11)0.0219 (11)0.0056 (9)0.0056 (9)
C60.108 (2)0.0790 (17)0.0462 (12)0.0412 (17)0.0197 (14)0.0183 (11)
C70.146 (3)0.121 (3)0.0694 (19)0.058 (3)0.007 (2)0.0386 (18)
C80.126 (3)0.175 (4)0.0665 (19)0.069 (3)0.021 (2)0.025 (2)
C90.092 (2)0.150 (3)0.0555 (16)0.038 (2)0.0197 (15)0.0054 (17)
C100.0602 (14)0.0992 (19)0.0511 (13)0.0207 (13)0.0109 (10)0.0032 (12)
C110.149 (3)0.0609 (15)0.0731 (18)0.0034 (19)0.0283 (19)0.0085 (13)
C120.141 (3)0.086 (2)0.119 (3)0.009 (2)0.037 (3)0.0099 (19)
C130.248 (5)0.0610 (17)0.124 (3)0.006 (3)0.077 (3)0.0092 (18)
C140.094 (2)0.252 (5)0.091 (2)0.026 (3)0.050 (2)0.034 (3)
C150.0438 (10)0.0480 (10)0.0454 (11)0.0018 (8)0.0037 (9)0.0044 (8)
C160.0408 (10)0.0645 (14)0.0692 (14)0.0028 (10)0.0016 (10)0.0007 (11)
C170.0476 (12)0.0628 (14)0.0837 (16)0.0145 (11)0.0034 (11)0.0003 (12)
C180.0598 (13)0.0526 (12)0.0661 (13)0.0085 (10)0.0035 (11)0.0047 (10)
C190.0394 (11)0.0879 (19)0.147 (3)0.0045 (13)0.0064 (14)0.0031 (19)
C200.095 (2)0.0532 (14)0.140 (3)0.0088 (14)0.026 (2)0.0021 (15)
Geometric parameters (Å, º) top
S1—C151.759 (2)C8—H8B0.9700
S1—C31.809 (2)C9—C141.523 (5)
N1—C151.328 (2)C9—C101.533 (3)
N1—C161.342 (3)C9—H90.9800
N2—C181.330 (3)C10—H10A0.9700
N2—C151.331 (2)C10—H10B0.9700
O1—C11.355 (2)C11—C121.528 (5)
O1—C41.447 (2)C11—C131.538 (4)
O2—C11.196 (2)C11—H110.9800
O3—C41.382 (2)C12—H12A0.9600
O3—C51.450 (2)C12—H12B0.9600
C1—C21.491 (3)C12—H12C0.9600
C2—C31.529 (2)C13—H13A0.9600
C2—H2A0.9700C13—H13B0.9600
C2—H2B0.9700C13—H13C0.9600
C3—C41.524 (3)C14—H14A0.9600
C3—H30.9800C14—H14B0.9600
C4—H40.9800C14—H14C0.9600
C5—C101.501 (3)C16—C171.372 (3)
C5—C61.533 (3)C16—C191.499 (3)
C5—H50.9800C17—C181.378 (3)
C6—C111.524 (5)C17—H170.9300
C6—C71.533 (4)C18—C201.503 (3)
C6—H60.9800C19—H19A0.9600
C7—C81.508 (5)C19—H19B0.9600
C7—H7A0.9700C19—H19C0.9600
C7—H7B0.9700C20—H20A0.9600
C8—C91.521 (5)C20—H20B0.9600
C8—H8A0.9700C20—H20C0.9600
C15—S1—C3101.37 (9)C10—C9—H9107.9
C15—N1—C16115.65 (17)C5—C10—C9111.7 (2)
C18—N2—C15115.50 (17)C5—C10—H10A109.3
C1—O1—C4110.11 (14)C9—C10—H10A109.3
C4—O3—C5114.79 (14)C5—C10—H10B109.3
O2—C1—O1121.9 (2)C9—C10—H10B109.3
O2—C1—C2128.1 (2)H10A—C10—H10B107.9
O1—C1—C2109.95 (16)C6—C11—C12113.5 (3)
C1—C2—C3104.55 (16)C6—C11—C13111.7 (3)
C1—C2—H2A110.8C12—C11—C13110.1 (3)
C3—C2—H2A110.8C6—C11—H11107.0
C1—C2—H2B110.8C12—C11—H11107.0
C3—C2—H2B110.8C13—C11—H11107.0
H2A—C2—H2B108.9C11—C12—H12A109.5
C4—C3—C2101.90 (15)C11—C12—H12B109.5
C4—C3—S1111.50 (13)H12A—C12—H12B109.5
C2—C3—S1108.79 (13)C11—C12—H12C109.5
C4—C3—H3111.4H12A—C12—H12C109.5
C2—C3—H3111.4H12B—C12—H12C109.5
S1—C3—H3111.4C11—C13—H13A109.5
O3—C4—O1109.53 (15)C11—C13—H13B109.5
O3—C4—C3108.01 (14)H13A—C13—H13B109.5
O1—C4—C3105.10 (14)C11—C13—H13C109.5
O3—C4—H4111.3H13A—C13—H13C109.5
O1—C4—H4111.3H13B—C13—H13C109.5
C3—C4—H4111.3C9—C14—H14A109.5
O3—C5—C10109.69 (17)C9—C14—H14B109.5
O3—C5—C6106.64 (17)H14A—C14—H14B109.5
C10—C5—C6113.2 (2)C9—C14—H14C109.5
O3—C5—H5109.1H14A—C14—H14C109.5
C10—C5—H5109.1H14B—C14—H14C109.5
C6—C5—H5109.1N1—C15—N2128.02 (18)
C11—C6—C5113.7 (2)N1—C15—S1118.55 (14)
C11—C6—C7114.7 (3)N2—C15—S1113.42 (14)
C5—C6—C7107.8 (2)N1—C16—C17120.6 (2)
C11—C6—H6106.7N1—C16—C19116.5 (2)
C5—C6—H6106.7C17—C16—C19122.9 (2)
C7—C6—H6106.7C16—C17—C18119.1 (2)
C8—C7—C6112.2 (3)C16—C17—H17120.5
C8—C7—H7A109.2C18—C17—H17120.5
C6—C7—H7A109.2N2—C18—C17121.1 (2)
C8—C7—H7B109.2N2—C18—C20117.6 (2)
C6—C7—H7B109.2C16—C19—H19A109.5
H7A—C7—H7B107.9C16—C19—H19B109.5
C7—C8—C9113.1 (3)H19A—C19—H19B109.5
C7—C8—H8A109.0C16—C19—H19C109.5
C9—C8—H8A109.0H19A—C19—H19C109.5
C7—C8—H8B109.0H19B—C19—H19C109.5
C9—C8—H8B109.0C18—C20—H20A109.5
H8A—C8—H8B107.8C18—C20—H20B109.5
C8—C9—C14113.7 (3)H20A—C20—H20B109.5
C8—C9—C10108.9 (3)C18—C20—H20C109.5
C14—C9—C10110.3 (3)H20A—C20—H20C109.5
C8—C9—H9107.9H20B—C20—H20C109.5
C14—C9—H9107.9
C4—O1—C1—O2171.7 (2)C7—C8—C9—C14178.0 (3)
C4—O1—C1—C28.6 (2)C7—C8—C9—C1054.5 (4)
O2—C1—C2—C3169.3 (2)O3—C5—C10—C9176.5 (2)
O1—C1—C2—C310.4 (2)C6—C5—C10—C957.6 (3)
C1—C2—C3—C423.61 (18)C8—C9—C10—C554.4 (3)
C1—C2—C3—S194.25 (16)C14—C9—C10—C5179.8 (3)
C15—S1—C3—C469.56 (14)C5—C6—C11—C1267.5 (3)
C15—S1—C3—C2178.84 (13)C7—C6—C11—C1257.3 (3)
C5—O3—C4—O172.27 (19)C5—C6—C11—C13167.3 (2)
C5—O3—C4—C3173.77 (16)C7—C6—C11—C1368.0 (3)
C1—O1—C4—O391.68 (17)C16—N1—C15—N20.3 (3)
C1—O1—C4—C324.14 (19)C16—N1—C15—S1178.91 (16)
C2—C3—C4—O388.10 (17)C18—N2—C15—N10.9 (3)
S1—C3—C4—O3156.00 (12)C18—N2—C15—S1178.30 (16)
C2—C3—C4—O128.76 (17)C3—S1—C15—N18.52 (18)
S1—C3—C4—O187.14 (15)C3—S1—C15—N2170.76 (15)
C4—O3—C5—C1084.5 (2)C15—N1—C16—C170.3 (3)
C4—O3—C5—C6152.61 (19)C15—N1—C16—C19180.0 (2)
O3—C5—C6—C1155.1 (3)N1—C16—C17—C180.3 (4)
C10—C5—C6—C11175.76 (19)C19—C16—C17—C18179.9 (2)
O3—C5—C6—C7176.5 (2)C15—N2—C18—C170.9 (3)
C10—C5—C6—C755.9 (3)C15—N2—C18—C20177.3 (2)
C11—C6—C7—C8177.6 (3)C16—C17—C18—N20.4 (4)
C5—C6—C7—C854.6 (3)C16—C17—C18—C20177.8 (2)
C6—C7—C8—C956.7 (4)
(II) (4R,5R)-5-[(2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-4-(4-methyl-1,3- thiazol-2-ylamino)-2,3,4,5-tetrahydrofuran-2-one top
Crystal data top
C18H28N2O3SDx = 1.200 Mg m3
Mr = 352.48Melting point = 466.5–468.3 K
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 826 reflections
a = 8.841 (3) Åθ = 3.1–23.1°
b = 11.203 (3) ŵ = 0.18 mm1
c = 19.692 (6) ÅT = 293 K
V = 1950.3 (10) Å3Prism, yellow
Z = 40.34 × 0.22 × 0.18 mm
F(000) = 760
Data collection top
Bruker SMART CCD area-detector
diffractometer
3997 independent reflections
Radiation source: fine-focus sealed tube2992 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.031
ϕ and ω scansθmax = 26.5°, θmin = 2.1°
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)
h = 711
Tmin = 0.913, Tmax = 0.970k = 1314
11333 measured reflectionsl = 2417
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.042H-atom parameters constrained
wR(F2) = 0.099 w = 1/[σ2(Fo2) + (0.0472P)2 + 0.1182P]
where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max = 0.013
3997 reflectionsΔρmax = 0.16 e Å3
221 parametersΔρmin = 0.17 e Å3
1 restraintAbsolute structure: Flack (1983), with how many Friedel pairs
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 0.03 (8)
Crystal data top
C18H28N2O3SV = 1950.3 (10) Å3
Mr = 352.48Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 8.841 (3) ŵ = 0.18 mm1
b = 11.203 (3) ÅT = 293 K
c = 19.692 (6) Å0.34 × 0.22 × 0.18 mm
Data collection top
Bruker SMART CCD area-detector
diffractometer
3997 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)
2992 reflections with I > 2σ(I)
Tmin = 0.913, Tmax = 0.970Rint = 0.031
11333 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.042H-atom parameters constrained
wR(F2) = 0.099Δρmax = 0.16 e Å3
S = 1.06Δρmin = 0.17 e Å3
3997 reflectionsAbsolute structure: Flack (1983), with how many Friedel pairs
221 parametersAbsolute structure parameter: 0.03 (8)
1 restraint
Special details top

Experimental. 1H NMR (500 MHz, CDCl3, δ, p.p.m.): 0.79 (3H, d, J = 6.9 Hz, H12), 0.88 (H, m, H10), 0.90 (3H, d, J = 7.1 Hz, H14), 0.96 (3H, d, J = 6.5 Hz, H15), 1.02 (2H, m, H10, H13), 1.27 (2H, m, H9), 1.67 (2H, m, H7), 2.05 (1H, m, H11), 2.19 (1H, m, H8), 2.26 (3H, s, H6'), 2.50 (1H, d, J = 18.1 Hz, H3), 3.32 (1H, dd, J = 18.1 and 7.3 Hz, H3), 3.55 (1H, dt, J = 10.7 and 6.6 Hz, H6), 4.22 (1H, d, J = 6.9 Hz, H4), 5.73 (1H, s, H5), 6.17 (1H, s, H5'); 13C NMR (125 MHz, CDCl3, δ, p.p.m): 15.6 (C15), 17.2 (C6'), 20.9 (C14), 23.1 (C10), 25.6 (C13), 31.4 (C8), 34.2 (C3, C9), 39.7 (C7), 47.6 (C11), 57.3 (C4), 77.7 (C6), 102.4 (C5), 103.7 (C5'), 138.3 (C2'), 166.6 (C5); IR (KBr, cm−1): ν 1778 (C=O).

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 (Å2) top
xyzUiso*/Ueq
S10.14879 (8)0.22367 (6)0.22496 (4)0.0693 (2)
N10.0071 (2)0.32833 (17)0.12363 (9)0.0540 (5)
H10.03080.27490.09730.065*
N20.0458 (2)0.39337 (16)0.23518 (9)0.0497 (4)
O10.32722 (17)0.33004 (13)0.05899 (8)0.0572 (4)
O20.2752 (2)0.30145 (18)0.05033 (9)0.0882 (6)
O30.34001 (15)0.50952 (11)0.11756 (7)0.0452 (3)
C10.2406 (3)0.3434 (2)0.00327 (12)0.0560 (6)
C20.1045 (3)0.4157 (2)0.01931 (10)0.0513 (5)
H2A0.01390.37770.00190.062*
H2B0.11270.49500.00010.062*
C30.1008 (2)0.42168 (19)0.09624 (10)0.0426 (5)
H30.06650.50030.11180.051*
C40.2669 (2)0.40099 (18)0.11472 (11)0.0449 (5)
H40.27590.35820.15800.054*
C50.4856 (2)0.50793 (18)0.15171 (10)0.0411 (5)
H50.53940.43420.14000.049*
C60.5742 (2)0.6141 (2)0.12578 (11)0.0494 (5)
H60.51560.68530.13760.059*
C70.7230 (3)0.6217 (3)0.16558 (14)0.0796 (8)
H7A0.78420.55200.15550.095*
H7B0.77870.69170.15090.095*
C80.6973 (4)0.6288 (3)0.24116 (13)0.0850 (9)
H8A0.64350.70190.25170.102*
H8B0.79420.63140.26420.102*
C90.6075 (3)0.5236 (2)0.26728 (11)0.0640 (6)
H90.66710.45130.25910.077*
C100.4604 (2)0.5124 (2)0.22740 (11)0.0570 (6)
H10A0.40820.44050.24160.068*
H10B0.39590.57990.23800.068*
C110.5946 (3)0.6162 (2)0.04876 (12)0.0617 (6)
H110.49450.60160.02900.074*
C120.6960 (4)0.5201 (4)0.02260 (15)0.1237 (15)
H12A0.69630.52160.02610.186*
H12B0.66010.44390.03800.186*
H12C0.79690.53290.03910.186*
C130.6448 (6)0.7383 (4)0.02369 (15)0.1303 (16)
H13A0.74580.75410.03930.196*
H13B0.57760.79830.04100.196*
H13C0.64290.73970.02510.196*
C140.5763 (4)0.5313 (4)0.34349 (13)0.1102 (12)
H14A0.51310.59910.35260.165*
H14B0.67020.53970.36750.165*
H14C0.52600.45990.35820.165*
C150.0212 (2)0.32530 (19)0.19166 (11)0.0479 (5)
C160.0043 (3)0.3657 (2)0.30031 (11)0.0546 (6)
C170.1064 (3)0.2785 (2)0.30402 (13)0.0653 (6)
H170.14910.25090.34420.078*
C180.0602 (4)0.4356 (3)0.35836 (12)0.0815 (9)
H18A0.02350.51620.35650.122*
H18B0.16860.43570.35530.122*
H18C0.02980.39960.40050.122*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0646 (4)0.0651 (4)0.0783 (4)0.0231 (3)0.0202 (3)0.0026 (3)
N10.0498 (11)0.0667 (12)0.0454 (10)0.0211 (10)0.0031 (9)0.0102 (9)
N20.0503 (10)0.0568 (10)0.0418 (10)0.0091 (9)0.0029 (8)0.0002 (8)
O10.0433 (8)0.0552 (9)0.0733 (10)0.0090 (7)0.0017 (8)0.0080 (8)
O20.0916 (14)0.1071 (15)0.0658 (12)0.0254 (12)0.0211 (11)0.0296 (11)
O30.0340 (7)0.0455 (8)0.0562 (8)0.0017 (6)0.0077 (7)0.0043 (7)
C10.0530 (14)0.0582 (14)0.0568 (14)0.0021 (12)0.0065 (13)0.0054 (12)
C20.0473 (12)0.0646 (14)0.0421 (12)0.0068 (11)0.0030 (10)0.0014 (10)
C30.0367 (10)0.0521 (12)0.0389 (11)0.0020 (9)0.0019 (8)0.0029 (9)
C40.0395 (11)0.0464 (11)0.0487 (12)0.0028 (10)0.0008 (10)0.0053 (10)
C50.0339 (10)0.0433 (11)0.0463 (11)0.0039 (9)0.0041 (9)0.0000 (9)
C60.0425 (12)0.0519 (12)0.0537 (13)0.0044 (10)0.0042 (10)0.0000 (10)
C70.0581 (16)0.110 (2)0.0708 (17)0.0362 (16)0.0157 (14)0.0111 (16)
C80.085 (2)0.097 (2)0.0740 (19)0.0230 (17)0.0324 (16)0.0075 (16)
C90.0639 (15)0.0769 (16)0.0511 (13)0.0088 (14)0.0087 (12)0.0038 (12)
C100.0495 (13)0.0745 (15)0.0470 (12)0.0027 (12)0.0018 (11)0.0004 (12)
C110.0524 (14)0.0797 (16)0.0531 (14)0.0112 (13)0.0006 (11)0.0075 (12)
C120.105 (3)0.196 (4)0.070 (2)0.060 (3)0.0264 (19)0.003 (2)
C130.173 (4)0.138 (3)0.080 (2)0.076 (3)0.007 (2)0.038 (2)
C140.127 (3)0.156 (3)0.0478 (16)0.008 (3)0.0198 (18)0.0037 (18)
C150.0389 (11)0.0500 (12)0.0548 (13)0.0058 (10)0.0061 (10)0.0004 (10)
C160.0561 (13)0.0581 (14)0.0496 (13)0.0041 (12)0.0088 (11)0.0081 (10)
C170.0657 (16)0.0673 (15)0.0630 (15)0.0017 (14)0.0214 (12)0.0155 (13)
C180.106 (2)0.096 (2)0.0426 (14)0.0075 (18)0.0019 (14)0.0019 (13)
Geometric parameters (Å, º) top
S1—C171.715 (3)C7—H7B0.9700
S1—C151.732 (2)C8—C91.511 (4)
N1—C151.363 (3)C8—H8A0.9700
N1—C31.439 (3)C8—H8B0.9700
N1—H10.8600C9—C101.524 (3)
N2—C151.291 (3)C9—C141.528 (3)
N2—C161.392 (3)C9—H90.9800
O1—C11.347 (3)C10—H10A0.9700
O1—C41.456 (3)C10—H10B0.9700
O2—C11.195 (3)C11—C121.493 (4)
O3—C41.378 (2)C11—C131.521 (4)
O3—C51.452 (2)C11—H110.9800
C1—C21.484 (3)C12—H12A0.9600
C2—C31.517 (3)C12—H12B0.9600
C2—H2A0.9700C12—H12C0.9600
C2—H2B0.9700C13—H13A0.9600
C3—C41.531 (3)C13—H13B0.9600
C3—H30.9800C13—H13C0.9600
C4—H40.9800C14—H14A0.9600
C5—C101.508 (3)C14—H14B0.9600
C5—C61.513 (3)C14—H14C0.9600
C5—H50.9800C16—C171.332 (3)
C6—C111.527 (3)C16—C181.498 (3)
C6—C71.534 (3)C17—H170.9300
C6—H60.9800C18—H18A0.9600
C7—C81.508 (4)C18—H18B0.9600
C7—H7A0.9700C18—H18C0.9600
C17—S1—C1588.06 (11)C8—C9—C10109.7 (2)
C15—N1—C3119.47 (17)C8—C9—C14112.7 (2)
C15—N1—H1120.0C10—C9—C14110.9 (2)
C3—N1—H1120.0C8—C9—H9107.8
C15—N2—C16109.52 (18)C10—C9—H9107.8
C1—O1—C4110.18 (16)C14—C9—H9107.8
C4—O3—C5115.06 (14)C5—C10—C9112.71 (18)
O2—C1—O1122.0 (2)C5—C10—H10A109.1
O2—C1—C2127.6 (2)C9—C10—H10A109.1
O1—C1—C2110.39 (19)C5—C10—H10B109.1
C1—C2—C3104.74 (18)C9—C10—H10B109.1
C1—C2—H2A110.8H10A—C10—H10B107.8
C3—C2—H2A110.8C12—C11—C13111.2 (3)
C1—C2—H2B110.8C12—C11—C6113.7 (2)
C3—C2—H2B110.8C13—C11—C6111.8 (2)
H2A—C2—H2B108.9C12—C11—H11106.6
N1—C3—C2110.78 (18)C13—C11—H11106.6
N1—C3—C4110.69 (17)C6—C11—H11106.6
C2—C3—C4102.12 (17)C11—C12—H12A109.5
N1—C3—H3111.1C11—C12—H12B109.5
C2—C3—H3111.1H12A—C12—H12B109.5
C4—C3—H3111.1C11—C12—H12C109.5
O3—C4—O1109.90 (16)H12A—C12—H12C109.5
O3—C4—C3109.03 (17)H12B—C12—H12C109.5
O1—C4—C3104.76 (16)C11—C13—H13A109.5
O3—C4—H4111.0C11—C13—H13B109.5
O1—C4—H4111.0H13A—C13—H13B109.5
C3—C4—H4111.0C11—C13—H13C109.5
O3—C5—C10109.11 (16)H13A—C13—H13C109.5
O3—C5—C6107.03 (15)H13B—C13—H13C109.5
C10—C5—C6112.57 (17)C9—C14—H14A109.5
O3—C5—H5109.3C9—C14—H14B109.5
C10—C5—H5109.3H14A—C14—H14B109.5
C6—C5—H5109.3C9—C14—H14C109.5
C5—C6—C11114.12 (18)H14A—C14—H14C109.5
C5—C6—C7108.40 (18)H14B—C14—H14C109.5
C11—C6—C7113.9 (2)N2—C15—N1123.60 (19)
C5—C6—H6106.6N2—C15—S1115.84 (17)
C11—C6—H6106.6N1—C15—S1120.53 (16)
C7—C6—H6106.6C17—C16—N2115.4 (2)
C8—C7—C6112.2 (2)C17—C16—C18126.8 (2)
C8—C7—H7A109.2N2—C16—C18117.8 (2)
C6—C7—H7A109.2C16—C17—S1111.15 (18)
C8—C7—H7B109.2C16—C17—H17124.5
C6—C7—H7B109.2S1—C17—H17124.5
H7A—C7—H7B107.9C16—C18—H18A109.5
C7—C8—C9112.0 (2)C16—C18—H18B109.5
C7—C8—H8A109.2H18A—C18—H18B109.5
C9—C8—H8A109.2C16—C18—H18C109.5
C7—C8—H8B109.2H18A—C18—H18C109.5
C9—C8—H8B109.2H18B—C18—H18C109.5
H8A—C8—H8B107.9
C4—O1—C1—O2173.7 (2)C11—C6—C7—C8175.6 (2)
C4—O1—C1—C25.8 (2)C6—C7—C8—C957.5 (3)
O2—C1—C2—C3168.0 (3)C7—C8—C9—C1054.2 (3)
O1—C1—C2—C312.4 (2)C7—C8—C9—C14178.3 (3)
C15—N1—C3—C2174.26 (19)O3—C5—C10—C9174.29 (19)
C15—N1—C3—C473.2 (2)C6—C5—C10—C955.7 (3)
C1—C2—C3—N193.8 (2)C8—C9—C10—C553.4 (3)
C1—C2—C3—C424.1 (2)C14—C9—C10—C5178.5 (2)
C5—O3—C4—O181.46 (19)C5—C6—C11—C1268.7 (3)
C5—O3—C4—C3164.24 (15)C7—C6—C11—C1256.5 (3)
C1—O1—C4—O395.47 (19)C5—C6—C11—C13164.4 (3)
C1—O1—C4—C321.5 (2)C7—C6—C11—C1370.3 (3)
N1—C3—C4—O3151.98 (16)C16—N2—C15—N1178.0 (2)
C2—C3—C4—O390.1 (2)C16—N2—C15—S10.1 (2)
N1—C3—C4—O190.43 (18)C3—N1—C15—N28.6 (3)
C2—C3—C4—O127.5 (2)C3—N1—C15—S1173.32 (16)
C4—O3—C5—C1080.7 (2)C17—S1—C15—N20.16 (18)
C4—O3—C5—C6157.22 (16)C17—S1—C15—N1178.03 (19)
O3—C5—C6—C1157.0 (2)C15—N2—C16—C170.1 (3)
C10—C5—C6—C11176.81 (19)C15—N2—C16—C18179.8 (2)
O3—C5—C6—C7174.89 (19)N2—C16—C17—S10.2 (3)
C10—C5—C6—C755.1 (3)C18—C16—C17—S1179.7 (2)
C5—C6—C7—C856.1 (3)C15—S1—C17—C160.19 (19)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O2i0.862.132.898 (2)149
C10—H10B···S1ii0.972.813.751 (3)163
Symmetry codes: (i) x1/2, y+1/2, z; (ii) x, y+1/2, z+1/2.

Experimental details

(I)(II)
Crystal data
Chemical formulaC20H30N2O3SC18H28N2O3S
Mr378.52352.48
Crystal system, space groupOrthorhombic, P212121Orthorhombic, P212121
Temperature (K)293293
a, b, c (Å)8.825 (4), 14.401 (6), 17.033 (7)8.841 (3), 11.203 (3), 19.692 (6)
V3)2164.5 (15)1950.3 (10)
Z44
Radiation typeMo KαMo Kα
µ (mm1)0.170.18
Crystal size (mm)0.42 × 0.32 × 0.260.34 × 0.22 × 0.18
Data collection
DiffractometerBruker SMART CCD area-detector
diffractometer
Bruker SMART CCD area-detector
diffractometer
Absorption correctionMulti-scan
(SADABS; Sheldrick, 1996)
Multi-scan
(SADABS; Sheldrick, 1996)
Tmin, Tmax0.977, 0.9960.913, 0.970
No. of measured, independent and
observed [I > 2σ(I)] reflections
12564, 4425, 3686 11333, 3997, 2992
Rint0.0290.031
(sin θ/λ)max1)0.6270.627
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.037, 0.097, 1.06 0.042, 0.099, 1.06
No. of reflections44253997
No. of parameters242221
No. of restraints01
H-atom treatmentH-atom parameters constrainedH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.15, 0.150.16, 0.17
Absolute structureFlack (1983), with how many Friedel pairsFlack (1983), with how many Friedel pairs
Absolute structure parameter0.00 (7)0.03 (8)

Computer programs: SMART (Bruker, 1999), SMART, SAINT (Bruker, 1999), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXTL (Bruker, 1997), SHELXTL.

Selected geometric parameters (Å, º) for (I) top
S1—C151.759 (2)N1—C161.342 (3)
S1—C31.809 (2)N2—C181.330 (3)
N1—C151.328 (2)N2—C151.331 (2)
C4—C3—C2101.90 (15)C2—C3—S1108.79 (13)
C4—C3—S1111.50 (13)
C1—C2—C3—S194.25 (16)S1—C3—C4—O187.14 (15)
C15—S1—C3—C469.56 (14)C3—S1—C15—N18.52 (18)
C15—S1—C3—C2178.84 (13)C3—S1—C15—N2170.76 (15)
S1—C3—C4—O3156.00 (12)
Selected geometric parameters (Å, º) for (II) top
S1—C171.715 (3)N2—C151.291 (3)
S1—C151.732 (2)N2—C161.392 (3)
N1—C151.363 (3)C16—C171.332 (3)
N1—C31.439 (3)
N1—C3—C2110.78 (18)C2—C3—C4102.12 (17)
N1—C3—C4110.69 (17)
C15—N1—C3—C473.2 (2)N1—C3—C4—O3151.98 (16)
C1—C2—C3—C424.1 (2)C2—C3—C4—O390.1 (2)
C5—O3—C4—C3164.24 (15)N1—C3—C4—O190.43 (18)
C1—O1—C4—C321.5 (2)C2—C3—C4—O127.5 (2)
Hydrogen-bond geometry (Å, º) for (II) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O2i0.8602.1302.898 (2)149
C10—H10B···S1ii0.972.813.751 (3)163
Symmetry codes: (i) x1/2, y+1/2, z; (ii) x, y+1/2, z+1/2.
 

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