Ethyl 6-ethoxy-carbonyl-methyl-4-(2-hydroxy-phen-yl)-2-oxo-1,2,3,4-tetra-hydro-pyrimidine-5-carboxyl-ate.

The title compound, C(17)H(20)N(2)O(6), belongs to the monastrol-type of anti-cancer agents and was selected for crystal structure determination in order to confirm its mol-ecular structure and explore some aspects of its structure-activity relationships. The central tetra-hydro-pyrimidine ring has a flat-envelope conformation. The 4-hydroxy-phenyl group occupies a pseudo-axial position and is inclined at an angle of 87.7 (2)° to the mean plane of the heterocyclic ring. Of the two ethyl ester groups, one (in the 5-position) is in a coplanar and the other (in the 6-position) is in a perpendicular orientation with respect to the heterocyclic plane. There is a three-dimensional hydrogen-bonding network in which all hydrogen-bond donors and acceptors are involved.

Related literature

For related literature, see: Allen (2002 ▶); Azizian et al. (2007 ▶); Qing-Fang et al. (2007 ▶); Endow & Baker (2003 ▶); Kettmann & Svetlík (1997 ▶); Světlík et al. (1991 ▶); Wood & Bergnes (2004 ▶).

Experimental

Crystal data

C17H20N2O6

M = 348.35

Triclinic,

a = 8.783 (2) Å

b = 9.336 (3) Å

c = 11.415 (4) Å

α = 71.47 (4)°

β = 82.78 (5)°

γ = 75.05 (4)°

V = 856.5 (5) Å3

Z = 2

Mo Kα radiation

μ = 0.10 mm−1

T = 296 (2) K

0.30 × 0.25 × 0.20 mm

Data collection

Siemens P4 diffractometer

Absorption correction: none

5849 measured reflections

4950 independent reflections

3935 reflections with I > 2σ(I)

R int = 0.040

3 standard reflections every 97 reflections intensity decay: none

Refinement

R[F 2 > 2σ(F 2)] = 0.057

wR(F 2) = 0.174

S = 1.04

4950 reflections

229 parameters

H-atom parameters constrained

Δρmax = 0.31 e Å−3

Δρmin = −0.32 e Å−3

Data collection: XSCANS (Siemens, 1991 ▶); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2003 ▶); software used to prepare material for publication: SHELXL97.

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808012683/wk2083sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808012683/wk2083Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C17H20N2O6	Z = 2
Mr = 348.35	F000 = 368
Triclinic, P1	Dx = 1.351 Mg m−3
Hall symbol: -P 1	Melting point: 489 K
a = 8.783 (2) Å	Mo Kα radiation λ = 0.71073 Å
b = 9.336 (3) Å	Cell parameters from 20 reflections
c = 11.415 (4) Å	θ = 7–18º
α = 71.47 (4)º	µ = 0.10 mm−1
β = 82.78 (5)º	T = 296 (2) K
γ = 75.05 (4)º	Prism, colourless
V = 856.5 (5) Å3	0.30 × 0.25 × 0.20 mm

Siemens P4 diffractometer	Rint = 0.040
Radiation source: fine-focus sealed tube	θmax = 30.0º
Monochromator: graphite	θmin = 1.9º
T = 296(2) K	h = −1→12
ω/2θ scans	k = −12→12
Absorption correction: none	l = −16→16
5849 measured reflections	3 standard reflections
4950 independent reflections	every 97 reflections
3935 reflections with I > 2σ(I)	intensity decay: none

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.057	H-atom parameters constrained
wR(F2) = 0.174	w = 1/[σ2(Fo2) + (0.0972P)2 + 0.1877P] where P = (Fo2 + 2Fc2)/3
S = 1.04	(Δ/σ)max = 0.001
4950 reflections	Δρmax = 0.31 e Å−3
229 parameters	Δρmin = −0.31 e Å−3
Primary atom site location: structure-invariant direct methods	Extinction correction: none

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.

	x	y	z	Uiso*/Ueq
N1	0.10214 (15)	0.47412 (12)	0.13671 (11)	0.0350 (3)
H1	0.0749	0.5465	0.0692	0.042*
C2	0.11515 (15)	0.32189 (14)	0.13967 (13)	0.0315 (3)
O1	0.06497 (13)	0.29448 (11)	0.05495 (10)	0.0408 (3)
N3	0.17844 (14)	0.21317 (12)	0.24052 (11)	0.0344 (3)
H3	0.1615	0.1218	0.2584	0.041*
C4	0.27587 (15)	0.24302 (13)	0.32230 (12)	0.0304 (3)
H4	0.2669	0.1704	0.4051	0.037*
C5	0.21064 (15)	0.40660 (14)	0.33107 (12)	0.0307 (3)
C6	0.13046 (15)	0.51589 (13)	0.23577 (12)	0.0302 (3)
C7	0.44794 (15)	0.21163 (14)	0.27695 (12)	0.0315 (3)
C8	0.51674 (18)	0.32744 (17)	0.19754 (16)	0.0431 (3)
H8	0.4584	0.4297	0.1753	0.052*
C9	0.6717 (2)	0.2929 (2)	0.15072 (18)	0.0521 (4)
H9	0.7161	0.3715	0.0975	0.063*
C10	0.75860 (19)	0.1417 (2)	0.18372 (18)	0.0519 (4)
H10	0.8617	0.1182	0.1519	0.062*
C11	0.69370 (19)	0.02481 (19)	0.26383 (17)	0.0469 (4)
H11	0.7536	−0.0768	0.2867	0.056*
C12	0.53881 (16)	0.05890 (15)	0.31031 (14)	0.0353 (3)
O2	0.46665 (14)	−0.05252 (12)	0.38635 (12)	0.0489 (3)
H2	0.5328	−0.1341	0.4106	0.073*
C13	0.24784 (17)	0.43413 (15)	0.44190 (13)	0.0367 (3)
O3	0.31840 (19)	0.33335 (14)	0.52678 (12)	0.0602 (4)
O4	0.19773 (16)	0.58055 (12)	0.44378 (11)	0.0485 (3)
C14	0.2312 (3)	0.6194 (2)	0.55027 (18)	0.0582 (5)
H14A	0.3441	0.6037	0.5551	0.070*
H14B	0.1912	0.5542	0.6260	0.070*
C15	0.1516 (3)	0.7858 (2)	0.5332 (2)	0.0668 (6)
H15A	0.1992	0.8497	0.4624	0.100*
H15B	0.1627	0.8131	0.6055	0.100*
H15C	0.0417	0.8016	0.5208	0.100*
C16	0.06044 (17)	0.68574 (14)	0.22359 (14)	0.0363 (3)
H16A	−0.0109	0.7274	0.1562	0.044*
H16B	−0.0022	0.6925	0.2988	0.044*
C17	0.17511 (19)	0.78803 (15)	0.20076 (15)	0.0403 (3)
O5	0.13786 (18)	0.91436 (13)	0.21651 (16)	0.0651 (4)
O6	0.31602 (15)	0.72710 (13)	0.15956 (13)	0.0521 (3)
C18	0.4286 (3)	0.8264 (3)	0.1244 (3)	0.0778 (7)
H18A	0.4017	0.9049	0.0460	0.093*
H18B	0.4240	0.8786	0.1864	0.093*
C19	0.5842 (3)	0.7343 (3)	0.1139 (4)	0.0954 (9)
H19A	0.6129	0.6613	0.1931	0.143*
H19B	0.6572	0.8004	0.0864	0.143*
H19C	0.5870	0.6792	0.0553	0.143*

	U11	U22	U33	U12	U13	U23
N1	0.0449 (6)	0.0191 (5)	0.0410 (6)	−0.0060 (4)	−0.0108 (5)	−0.0068 (4)
C2	0.0302 (6)	0.0220 (5)	0.0430 (7)	−0.0070 (4)	−0.0017 (5)	−0.0100 (5)
O1	0.0490 (6)	0.0278 (5)	0.0503 (6)	−0.0086 (4)	−0.0120 (5)	−0.0145 (4)
N3	0.0371 (6)	0.0183 (4)	0.0485 (6)	−0.0078 (4)	−0.0076 (5)	−0.0076 (4)
C4	0.0316 (6)	0.0192 (5)	0.0374 (6)	−0.0034 (4)	−0.0032 (5)	−0.0057 (4)
C5	0.0309 (6)	0.0208 (5)	0.0386 (6)	−0.0023 (4)	−0.0031 (5)	−0.0086 (4)
C6	0.0301 (6)	0.0200 (5)	0.0400 (6)	−0.0040 (4)	−0.0043 (5)	−0.0086 (4)
C7	0.0306 (6)	0.0246 (5)	0.0377 (6)	−0.0014 (4)	−0.0050 (5)	−0.0098 (5)
C8	0.0376 (7)	0.0299 (6)	0.0546 (9)	−0.0049 (5)	0.0012 (6)	−0.0062 (6)
C9	0.0421 (8)	0.0477 (9)	0.0610 (10)	−0.0127 (7)	0.0082 (7)	−0.0108 (7)
C10	0.0331 (7)	0.0566 (10)	0.0660 (11)	−0.0028 (7)	0.0024 (7)	−0.0262 (8)
C11	0.0364 (7)	0.0375 (7)	0.0644 (10)	0.0053 (6)	−0.0075 (7)	−0.0210 (7)
C12	0.0345 (6)	0.0257 (6)	0.0450 (7)	−0.0006 (5)	−0.0095 (5)	−0.0118 (5)
O2	0.0458 (6)	0.0227 (5)	0.0677 (8)	−0.0004 (4)	−0.0063 (5)	−0.0039 (5)
C13	0.0402 (7)	0.0268 (6)	0.0403 (7)	−0.0018 (5)	−0.0062 (5)	−0.0094 (5)
O3	0.0838 (10)	0.0372 (6)	0.0517 (7)	0.0105 (6)	−0.0301 (7)	−0.0116 (5)
O4	0.0702 (8)	0.0307 (5)	0.0453 (6)	0.0010 (5)	−0.0188 (5)	−0.0164 (4)
C14	0.0785 (13)	0.0520 (10)	0.0517 (10)	−0.0078 (9)	−0.0171 (9)	−0.0264 (8)
C15	0.0932 (16)	0.0557 (11)	0.0642 (12)	−0.0218 (11)	0.0058 (11)	−0.0351 (10)
C16	0.0368 (6)	0.0207 (5)	0.0507 (8)	0.0016 (5)	−0.0126 (6)	−0.0121 (5)
C17	0.0508 (8)	0.0217 (5)	0.0483 (8)	−0.0047 (5)	−0.0154 (6)	−0.0082 (5)
O5	0.0715 (9)	0.0265 (5)	0.1037 (11)	−0.0072 (5)	−0.0159 (8)	−0.0272 (6)
O6	0.0534 (7)	0.0329 (5)	0.0741 (8)	−0.0180 (5)	0.0064 (6)	−0.0185 (5)
C18	0.0722 (14)	0.0501 (11)	0.116 (2)	−0.0352 (10)	0.0059 (13)	−0.0184 (12)
C19	0.0650 (14)	0.0790 (17)	0.154 (3)	−0.0359 (13)	0.0172 (16)	−0.0439 (18)

N1—C6	1.3761 (18)	C12—O2	1.366 (2)
N1—C2	1.3859 (16)	O2—H2	0.8200
N1—H1	0.8600	C13—O3	1.2161 (19)
C2—O1	1.2319 (17)	C13—O4	1.3299 (17)
C2—N3	1.3385 (19)	O4—C14	1.456 (2)
N3—C4	1.4733 (18)	C14—C15	1.490 (3)
N3—H3	0.8600	C14—H14A	0.9700
C4—C5	1.5172 (17)	C14—H14B	0.9700
C4—C7	1.5196 (19)	C15—H15A	0.9600
C4—H4	0.9800	C15—H15B	0.9600
C5—C6	1.3553 (19)	C15—H15C	0.9600
C5—C13	1.458 (2)	C16—C17	1.505 (2)
C6—C16	1.5134 (17)	C16—H16A	0.9700
C7—C8	1.390 (2)	C16—H16B	0.9700
C7—C12	1.3997 (18)	C17—O5	1.2047 (18)
C8—C9	1.393 (2)	C17—O6	1.318 (2)
C8—H8	0.9300	O6—C18	1.461 (2)
C9—C10	1.376 (3)	C18—C19	1.428 (4)
C9—H9	0.9300	C18—H18A	0.9700
C10—C11	1.381 (3)	C18—H18B	0.9700
C10—H10	0.9300	C19—H19A	0.9600
C11—C12	1.391 (2)	C19—H19B	0.9600
C11—H11	0.9300	C19—H19C	0.9600
C6—N1—C2	123.64 (12)	C12—O2—H2	109.5
C6—N1—H1	118.2	O3—C13—O4	121.72 (14)
C2—N1—H1	118.2	O3—C13—C5	123.83 (13)
O1—C2—N3	124.46 (12)	O4—C13—C5	114.46 (12)
O1—C2—N1	119.97 (13)	C13—O4—C14	118.33 (13)
N3—C2—N1	115.52 (12)	O4—C14—C15	107.06 (16)
C2—N3—C4	122.97 (11)	O4—C14—H14A	110.3
C2—N3—H3	118.5	C15—C14—H14A	110.3
C4—N3—H3	118.5	O4—C14—H14B	110.3
N3—C4—C5	109.07 (11)	C15—C14—H14B	110.3
N3—C4—C7	109.88 (11)	H14A—C14—H14B	108.6
C5—C4—C7	113.81 (11)	C14—C15—H15A	109.5
N3—C4—H4	108.0	C14—C15—H15B	109.5
C5—C4—H4	108.0	H15A—C15—H15B	109.5
C7—C4—H4	108.0	C14—C15—H15C	109.5
C6—C5—C13	125.23 (12)	H15A—C15—H15C	109.5
C6—C5—C4	119.05 (12)	H15B—C15—H15C	109.5
C13—C5—C4	115.65 (11)	C17—C16—C6	116.62 (12)
C5—C6—N1	119.39 (11)	C17—C16—H16A	108.1
C5—C6—C16	127.74 (12)	C6—C16—H16A	108.1
N1—C6—C16	112.86 (11)	C17—C16—H16B	108.1
C8—C7—C12	118.38 (13)	C6—C16—H16B	108.1
C8—C7—C4	122.55 (12)	H16A—C16—H16B	107.3
C12—C7—C4	118.97 (12)	O5—C17—O6	124.41 (16)
C7—C8—C9	121.11 (15)	O5—C17—C16	122.19 (16)
C7—C8—H8	119.4	O6—C17—C16	113.38 (12)
C9—C8—H8	119.4	C17—O6—C18	116.16 (15)
C10—C9—C8	119.64 (16)	C19—C18—O6	109.59 (19)
C10—C9—H9	120.2	C19—C18—H18A	109.8
C8—C9—H9	120.2	O6—C18—H18A	109.8
C9—C10—C11	120.39 (15)	C19—C18—H18B	109.8
C9—C10—H10	119.8	O6—C18—H18B	109.8
C11—C10—H10	119.8	H18A—C18—H18B	108.2
C10—C11—C12	120.09 (15)	C18—C19—H19A	109.5
C10—C11—H11	120.0	C18—C19—H19B	109.5
C12—C11—H11	120.0	H19A—C19—H19B	109.5
O2—C12—C11	122.69 (13)	C18—C19—H19C	109.5
O2—C12—C7	116.89 (13)	H19A—C19—H19C	109.5
C11—C12—C7	120.39 (15)	H19B—C19—H19C	109.5
C6—N1—C2—O1	168.78 (13)	C8—C9—C10—C11	−0.7 (3)
C6—N1—C2—N3	−8.8 (2)	C9—C10—C11—C12	1.0 (3)
O1—C2—N3—C4	162.57 (13)	C10—C11—C12—O2	177.68 (15)
N1—C2—N3—C4	−19.99 (19)	C10—C11—C12—C7	−0.3 (2)
C2—N3—C4—C5	36.47 (17)	C8—C7—C12—O2	−178.66 (14)
C2—N3—C4—C7	−88.92 (15)	C4—C7—C12—O2	−2.32 (19)
N3—C4—C5—C6	−27.05 (17)	C8—C7—C12—C11	−0.5 (2)
C7—C4—C5—C6	96.02 (15)	C4—C7—C12—C11	175.82 (13)
N3—C4—C5—C13	155.91 (12)	C6—C5—C13—O3	179.07 (16)
C7—C4—C5—C13	−81.02 (15)	C4—C5—C13—O3	−4.1 (2)
C13—C5—C6—N1	−179.52 (13)	C6—C5—C13—O4	−0.8 (2)
C4—C5—C6—N1	3.74 (19)	C4—C5—C13—O4	176.03 (12)
C13—C5—C6—C16	−1.2 (2)	O3—C13—O4—C14	0.9 (3)
C4—C5—C6—C16	−177.95 (12)	C5—C13—O4—C14	−179.27 (15)
C2—N1—C6—C5	16.6 (2)	C13—O4—C14—C15	−175.54 (17)
C2—N1—C6—C16	−161.95 (13)	C5—C6—C16—C17	71.9 (2)
N3—C4—C7—C8	93.30 (16)	N1—C6—C16—C17	−109.73 (15)
C5—C4—C7—C8	−29.33 (19)	C6—C16—C17—O5	−163.22 (15)
N3—C4—C7—C12	−82.87 (15)	C6—C16—C17—O6	18.42 (19)
C5—C4—C7—C12	154.50 (12)	O5—C17—O6—C18	−3.9 (3)
C12—C7—C8—C9	0.8 (2)	C16—C17—O6—C18	174.44 (17)
C4—C7—C8—C9	−175.40 (15)	C17—O6—C18—C19	164.6 (2)
C7—C8—C9—C10	−0.2 (3)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1i	0.86	1.97	2.788 (2)	159
O2—H2···O3ii	0.82	1.95	2.772 (2)	177
N3—H3···O5iii	0.86	2.20	3.0014 (18)	155

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O1i	0.86	1.97	2.788 (2)	159
O2—H2⋯O3ii	0.82	1.95	2.772 (2)	177
N3—H3⋯O5iii	0.86	2.20	3.0014 (18)	155

Symmetry codes: (i) ; (ii) ; (iii) .