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In the title compound, C10H14N2O3, a pyrimidine ring is fused with a piperidine ring. The pyrimidine ring is planar, whereas the piperidine ring adopts a half-chair conformation. The molecules of the title compound are connected via O-H...O intermolecular hydrogen bonds into infinite zigzag chains. The pyrimidine ring is involved in three C-H...[pi] interactions, which link the hydrogen-bonded chains into a three-dimensional framework.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S010827010500079X/sq1186sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S010827010500079X/sq1186Isup2.hkl
Contains datablock I

CCDC reference: 268113

Comment top

Pyrimidine derivatives substituted at the C5 or C6 position, and their nucleosides, have great biological significance because they exhibit a wide range of antiviral and anticancer activities (Kim et al., 1997; Pontikis et al., 1997; Botta et al., 1999). This prompted us to synthesize a series of novel 5-methyl-6-acyclic side-chain-substituted pyrimidine derivatives in order to evaluate their cytostatic and antiviral activities (Prekupec et al., 2004). Here, we report the structure of the title bicyclic product, (I), formed by intramolecular cyclization of the acyclic side chain with atom N1 of the pyrimidine ring.

The title piperido[1,2-c]pyrimidine-1-one derivative, (I), crystallizes in the noncentrosymmetric space group P212121 from a racemic mixture (Prekupec et al., 2004) by spontaneous resolution. A view of (I) (S configuration) is shown in Fig. 1 and selected geometric parameters are given in Table 1.

The molecule of (I) consists of two six-membered rings, fused via the common atoms N9 and C10. A survey of the Cambridge Structural Database (July 2004, Version 5.25; Allen, 2002) revealed that this is the first structure comprising these two fused heterocyclic rings, which have a carbonyl O atom at the 1-position and a methoxy group at the 3-position. The bond lengths and angles in (I) are well within the ranges reported for 4-methoxy-5-methyl-pyrimidine-2-ones (Brennan et al., 1986; Paquette et al., 2001) and piperidine-3-oles (Herdeis et al., 1996; Kirfel et al., 1996). As expected, the exception is the N9—C10 bond, which in (I) is significantly shorter (ca 0.09 Å) than the corresponding bond in the piperidine-3-oles, due to the delocalization effect of the pyrimidine ring.

The pyrimidine ring is planar. The largest observed deviation of the ring atoms from their mean plane is 0.008 (2) Å for atom C10. Atom C11 of the methoxy group is in a syn-periplanar position relative to atom N2 of the ring; the C11—O2—C3—N2 torsion angle is 2.1 (3)°. The piperidine ring adopts a half-chair conformation, in which atoms C6 and C7 are −0.369 (3) and 0.381 (2) Å, respectively, from the mean plane of the other ring atoms (C8/N9/C10/C5). The plane of atoms C8/N9/C10/C5 [torsion angle −0.1 (3)°] is almost coplanar with the pyrimidine ring, which is substantiated by the dihedral angle between their mean planes amounting to 1.1 (1)°. Furthermore, the hydroxyl atom O3 is in an axial position with respect to the piperidine ring, as illustrated by the O3—C7—C6—C5 and O3—C7—C8—N9 torsion angles (Table 1).

Molecules of (I) are linked into infinite zigzag chains by O—H···O intermolecular hydrogen bonds (Fig. 2 and Table 2). Atom O3 in the molecule at (x, y, z) acts as a donor to atom O1 in the molecule at (1/2 + x, 1/2 − y, 1 − z), so producing a spiral C(7) chain (Bernstein et al., 1995) running parallel to the [100] direction and generated by the 21 screw axis along (x, 1/4, 1/2). There are a number of C—H···π interactions that link these hydrogen-bonded chains (Fig. 3). The position of the methyl group atom H12B with respect to the pyrimidine ring in an adjacent molecule enables a geometric type-II C—H···π interaction (α 153° and θ 76°), according to the classification of Malone et al. (1997). The H12B···N9ii distance is shorter than the distance between the H atom and the pyrimidine-ring centroid [symmetry code: (ii) 2 − x, y − 1/2, 3/2 − z; Table 2]. The second shortest H···C contact is to atom C1, and the C12—H12B bond points more to the ring atom N9 than to the ring centroid (Cg). The C6—H61···Cgiii interaction exhibits a similar geometry [symmetry code: (iii) 1/2 + x, −1/2 − y, 1 − z]. The shortest H···C contact is to atom C1, but this could be classified as a geometric type-III interaction (α 120° and θ 69°). In the same class of interaction is C7—H7···Cgiii (α 123° and theta θ 65°), with the H7···C10iii and H7···C4iii distances being approximately equal and all other H···C contacts being longer than 3.37 Å. According to this observation, the C7—H7 bond points more to the C4—C10 bond of the pyrimidine ring. Thus, these three C—H···π interactions link the hydrogen-bonded chains into a three-dimensional framework.

Experimental top

Th synthesis of the racemic compound, (I), has been described by Prekupec et al. (2004). A mixture of 6-(4-chloro-3-hydroxybutyl)-2,4-dimethoxy-5-methylpyrimidine (250 mg, 0.95 mmol) in methanol (5 ml) was saturated with gaseous NH3. The flask was firmly stoppered and the reaction was stirred overnight at 333 K. The solvent was then evaporated under reduced pressure and the product was purified on a silica-gel column, using petroleum ether–ethyl acetate (1:1) as eluent. Crystals of (I) were isolated (144 mg; 72%; m.p. 482–484 K). Crystals suitable for X-ray diffraction were grown at room temperature from a very dilute ethanol solution (96%).

Refinement top

The H atoms attached to atom C11 and C12 were included in calculated positions as riding atoms, with C—H distances of 0.96 Å and with Uiso(H) = 1.5Ueq(C) Please check added text. All other H atoms were found in difference Fourier maps, and their coordinates and isotropic displacement parameters were refined freely. In the absence of significant anomalous scattering, the Flack (1983) parameter [−0.3 (14)] was inconclusive (Flack & Bernardinelli, 2000), and the Friedel equivalents were therefore merged prior to the final refinement. The enantiomer shown in Fig. 1 was chosen arbitrarily.

Computing details top

Data collection: STADI4 (Stoe & Cie, 1995); cell refinement: STADI4; data reduction: X-RED (Stoe & Cie, 1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97.

Figures top
[Figure 1] Fig. 1. A view of (I), with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
[Figure 2] Fig. 2. A crystal packing diagram of (I), viewed along [001], showing the formation of infinite zigzag chains parallel to [100]. Hydrogen bonds are indicated by dashed lines. [Symmetry code: (i) 1/2 + x, 1/2 − y, 1 − z.]
[Figure 3] Fig. 3. Part of the crystal structure of (I), showing the C—H···π interactions linking the hydrogen-bonded chains into a three-dimensional framework. The C12—H12B, C6—H61 and C7—H7 bonds point towards atom N9ii, atom C1iii and the C4—C10iii bond, respectively. C—H···π interactions are indicated by dotted lines, and the unit-cell box has been omitted for clarity. [Symmetry codes: (ii) 2 − x, y − 1/2, 3/2 − z; (iii) 1/2 + x, −1/2 − y, 1 − z.]
7-hydroxy-3-methoxy-4-methyl-5,6,7,8-tetrahydropyrido[1,2-c]pyrimidin- 1(8aH)-one top
Crystal data top
C10H14N2O3Dx = 1.371 Mg m3
Mr = 210.23Melting point = 482–484 K
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 25 reflections
a = 9.955 (4) Åθ = 3.8–11.4°
b = 6.9722 (12) ŵ = 0.10 mm1
c = 14.673 (4) ÅT = 293 K
V = 1018.4 (5) Å3Prismatic, colourless
Z = 40.55 × 0.29 × 0.21 mm
F(000) = 448
Data collection top
Philips PW1100 updated by Stoe & Cie
diffractometer
Rint = 0.047
Radiation source: fine-focus sealed tubeθmax = 29.0°, θmin = 3.2°
Graphite monochromatorh = 1313
ω scansk = 99
5738 measured reflectionsl = 2020
1574 independent reflections4 standard reflections every 120 min
1084 reflections with I > 2σ(I) intensity decay: 2.7%
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.040Hydrogen site location: difmap and geom
wR(F2) = 0.108H atoms treated by a mixture of independent and constrained refinement
S = 1.06 w = 1/[σ2(Fo2) + (0.0621P)2]
where P = (Fo2 + 2Fc2)/3
1574 reflections(Δ/σ)max = 0.001
168 parametersΔρmax = 0.16 e Å3
0 restraintsΔρmin = 0.13 e Å3
Crystal data top
C10H14N2O3V = 1018.4 (5) Å3
Mr = 210.23Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 9.955 (4) ŵ = 0.10 mm1
b = 6.9722 (12) ÅT = 293 K
c = 14.673 (4) Å0.55 × 0.29 × 0.21 mm
Data collection top
Philips PW1100 updated by Stoe & Cie
diffractometer
Rint = 0.047
5738 measured reflections4 standard reflections every 120 min
1574 independent reflections intensity decay: 2.7%
1084 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.0400 restraints
wR(F2) = 0.108H atoms treated by a mixture of independent and constrained refinement
S = 1.06Δρmax = 0.16 e Å3
1574 reflectionsΔρmin = 0.13 e Å3
168 parameters
Special details top

Experimental. 1H NMR (DMSO, δ, p.p.m.): 5.12 (OH, J = 3.4 Hz, d, 1H), 4.07–4.12 (H3', m, 1H), 3.81 (4-OCH3, s, 3H), 3.65–3.80 (H4', m, 2H), 2.63–2.86 (H1', m, 2H), 1.84 (CH3, s, 3H), 1.66–1.75 (H2', m, 2H)

13C NMR (DMSO, δ, p.p.m.): 168.50 (C2), 155.80 (C4), 154.32 (C6), 98.35 (C5), 61.72 (C4'), 53.57 (OCH3), 49.62 (C3'), 25.79 (C1'), 22.24 (C2'), 9.02 (CH3)

MS m/z: 210 M+

Analysis calculated for C10H14N2O3: C 57.13, H 6.71, N 13.33%; found: C 56.96, H 6.72, N 13.31%

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
N20.76699 (17)0.1903 (3)0.62330 (11)0.0435 (4)
N90.94119 (15)0.0018 (3)0.55901 (11)0.0396 (4)
O10.87177 (16)0.2766 (3)0.49195 (12)0.0612 (5)
O20.66276 (16)0.0845 (2)0.75222 (10)0.0558 (4)
O31.24107 (17)0.0960 (3)0.56460 (14)0.0713 (6)
H31.285 (3)0.009 (7)0.537 (2)0.119 (14)*
C10.8589 (2)0.1641 (3)0.55605 (14)0.0409 (5)
C30.7567 (2)0.0607 (3)0.68735 (13)0.0405 (5)
C40.83653 (19)0.1069 (3)0.69474 (13)0.0412 (5)
C51.0174 (3)0.3076 (4)0.6244 (2)0.0562 (6)
H510.960 (3)0.416 (5)0.639 (2)0.081 (9)*
H521.090 (3)0.294 (5)0.676 (2)0.084 (9)*
C61.0873 (3)0.3444 (4)0.5341 (2)0.0662 (8)
H611.148 (3)0.434 (5)0.5407 (19)0.069 (8)*
H621.017 (3)0.400 (5)0.489 (2)0.090 (10)*
C71.1469 (2)0.1597 (4)0.49922 (19)0.0553 (6)
H71.201 (2)0.163 (3)0.4430 (14)0.043 (6)*
C81.0378 (2)0.0142 (4)0.48332 (18)0.0518 (6)
H810.992 (3)0.046 (4)0.4321 (17)0.059 (7)*
H821.077 (3)0.117 (5)0.4733 (19)0.078 (9)*
C100.9286 (2)0.1327 (3)0.62650 (15)0.0406 (5)
C110.5759 (3)0.2489 (4)0.74521 (18)0.0722 (8)
H11A0.51360.24880.79510.108*
H11B0.52730.24360.68870.108*
H11C0.62880.36390.74710.108*
C120.8202 (3)0.2455 (4)0.77237 (17)0.0609 (7)
H12A0.75040.20110.81230.091*
H12B0.90300.25440.80560.091*
H12C0.79660.36950.74890.091*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N20.0448 (9)0.0373 (9)0.0482 (10)0.0032 (8)0.0012 (8)0.0010 (8)
N90.0370 (8)0.0341 (9)0.0479 (10)0.0008 (7)0.0006 (7)0.0020 (8)
O10.0631 (10)0.0568 (10)0.0635 (9)0.0127 (9)0.0102 (8)0.0233 (9)
O20.0546 (9)0.0538 (9)0.0589 (9)0.0112 (8)0.0137 (8)0.0093 (9)
O30.0521 (9)0.0637 (12)0.0981 (14)0.0080 (9)0.0059 (11)0.0227 (12)
C10.0408 (9)0.0353 (10)0.0467 (11)0.0017 (9)0.0012 (9)0.0049 (10)
C30.0377 (9)0.0380 (11)0.0456 (11)0.0027 (9)0.0016 (9)0.0001 (9)
C40.0379 (9)0.0363 (10)0.0494 (11)0.0046 (9)0.0028 (9)0.0057 (10)
C50.0500 (13)0.0370 (11)0.0816 (18)0.0062 (11)0.0093 (13)0.0111 (13)
C60.0577 (15)0.0394 (14)0.101 (2)0.0045 (12)0.0145 (15)0.0061 (14)
C70.0466 (12)0.0524 (14)0.0670 (15)0.0043 (11)0.0102 (12)0.0004 (13)
C80.0490 (12)0.0568 (16)0.0495 (13)0.0034 (11)0.0084 (11)0.0013 (12)
C100.0352 (9)0.0328 (10)0.0537 (12)0.0036 (9)0.0065 (9)0.0013 (9)
C110.0661 (16)0.0729 (19)0.0775 (17)0.0258 (15)0.0239 (15)0.0170 (17)
C120.0587 (14)0.0549 (15)0.0689 (14)0.0004 (12)0.0031 (12)0.0211 (13)
Geometric parameters (Å, º) top
N2—C31.308 (2)C5—H510.97 (3)
N2—C11.358 (3)C5—H521.04 (3)
N9—C101.369 (3)C6—C71.507 (4)
N9—C11.398 (3)C6—H610.87 (3)
N9—C81.474 (3)C6—H621.04 (3)
O1—C11.231 (2)C7—C81.504 (3)
O2—C31.344 (2)C7—H70.99 (2)
O2—C111.439 (3)C8—H810.91 (3)
O3—C71.413 (3)C8—H821.00 (3)
O3—H30.95 (4)C11—H11A0.9600
C3—C41.417 (3)C11—H11B0.9600
C4—C101.369 (3)C11—H11C0.9600
C4—C121.503 (3)C12—H12A0.9600
C5—C101.507 (3)C12—H12B0.9600
C5—C61.519 (4)C12—H12C0.9600
C3—N2—C1118.84 (17)O3—C7—C8111.8 (2)
C10—N9—C1121.55 (16)O3—C7—C6107.4 (2)
C10—N9—C8123.57 (18)C8—C7—C6110.2 (2)
C1—N9—C8114.86 (17)O3—C7—H7102.3 (12)
C3—O2—C11117.75 (17)C8—C7—H7106.3 (13)
C7—O3—H3105 (2)C6—C7—H7118.6 (14)
O1—C1—N2122.64 (18)N9—C8—C7113.9 (2)
O1—C1—N9118.60 (18)N9—C8—H81108.1 (16)
N2—C1—N9118.75 (16)C7—C8—H81109.3 (16)
N2—C3—O2118.56 (18)N9—C8—H82107.2 (16)
N2—C3—C4125.47 (18)C7—C8—H82110.8 (17)
O2—C3—C4115.97 (17)H81—C8—H82107 (2)
C10—C4—C3115.34 (17)C4—C10—N9120.01 (18)
C10—C4—C12122.9 (2)C4—C10—C5120.91 (19)
C3—C4—C12121.81 (19)N9—C10—C5119.08 (18)
C10—C5—C6115.0 (2)O2—C11—H11A109.5
C10—C5—H51106.2 (17)O2—C11—H11B109.5
C6—C5—H51109.4 (18)H11A—C11—H11B109.5
C10—C5—H52108.3 (18)O2—C11—H11C109.5
C6—C5—H52109.1 (15)H11A—C11—H11C109.5
H51—C5—H52109 (2)H11B—C11—H11C109.5
C7—C6—C5109.4 (2)C4—C12—H12A109.5
C7—C6—H61112 (2)C4—C12—H12B109.5
C5—C6—H61110.0 (19)H12A—C12—H12B109.5
C7—C6—H62111.4 (19)C4—C12—H12C109.5
C5—C6—H62108.2 (16)H12A—C12—H12C109.5
H61—C6—H62106 (3)H12B—C12—H12C109.5
C3—N2—C1—O1177.7 (2)C5—C6—C7—C861.4 (3)
C3—N2—C1—N91.4 (3)C10—N9—C8—C716.0 (3)
C10—N9—C1—O1177.49 (19)C1—N9—C8—C7165.62 (19)
C8—N9—C1—O10.9 (3)O3—C7—C8—N972.6 (3)
C10—N9—C1—N21.7 (3)C6—C7—C8—N946.7 (3)
C8—N9—C1—N2179.93 (19)C3—C4—C10—N91.9 (3)
C1—N2—C3—O2178.06 (17)C12—C4—C10—N9178.15 (19)
C1—N2—C3—C41.6 (3)C3—C4—C10—C5178.3 (2)
C11—O2—C3—N22.1 (3)C12—C4—C10—C51.7 (3)
C11—O2—C3—C4177.57 (19)C1—N9—C10—C42.0 (3)
N2—C3—C4—C101.8 (3)C8—N9—C10—C4179.8 (2)
O2—C3—C4—C10177.85 (18)C1—N9—C10—C5178.2 (2)
N2—C3—C4—C12178.2 (2)C8—N9—C10—C50.1 (3)
O2—C3—C4—C122.1 (3)C6—C5—C10—C4164.6 (2)
C10—C5—C6—C745.9 (3)C6—C5—C10—N915.5 (3)
C5—C6—C7—O360.6 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3···O1i0.94 (4)1.78 (4)2.709 (3)168 (3)
C12—H12B···Cgii0.963.083.956 (3)153
C12—H12B···N9ii0.963.043.856 (4)144
C12—H12B···C1ii0.963.174.116 (4)168
C6—H61···Cgiii0.87 (3)3.21 (3)3.718 (3)120 (2)
C6—H61···C1iii0.87 (3)3.00 (3)3.745 (4)144 (2)
C6—H61···N2iii0.87 (3)3.22 (3)3.788 (4)125 (2)
C7—H7···Cgiii0.99 (2)3.11 (2)3.736 (3)123 (1)
C7—H7···C10iii0.99 (2)2.86 (2)3.655 (3)138 (2)
C7—H7···C4iii0.99 (2)2.91 (2)3.783 (4)148 (2)
Symmetry codes: (i) x+1/2, y+1/2, z+1; (ii) x+2, y1/2, z+3/2; (iii) x+1/2, y1/2, z+1.

Experimental details

Crystal data
Chemical formulaC10H14N2O3
Mr210.23
Crystal system, space groupOrthorhombic, P212121
Temperature (K)293
a, b, c (Å)9.955 (4), 6.9722 (12), 14.673 (4)
V3)1018.4 (5)
Z4
Radiation typeMo Kα
µ (mm1)0.10
Crystal size (mm)0.55 × 0.29 × 0.21
Data collection
DiffractometerPhilips PW1100 updated by Stoe & Cie
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
5738, 1574, 1084
Rint0.047
(sin θ/λ)max1)0.683
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.040, 0.108, 1.06
No. of reflections1574
No. of parameters168
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.16, 0.13

Computer programs: STADI4 (Stoe & Cie, 1995), STADI4, X-RED (Stoe & Cie, 1995), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), PLATON (Spek, 2003), SHELXL97.

Selected geometric parameters (Å, º) top
N2—C31.308 (2)N9—C11.398 (3)
N2—C11.358 (3)C3—C41.417 (3)
N9—C101.369 (3)C4—C101.369 (3)
C3—N2—C1118.84 (17)N2—C3—C4125.47 (18)
C10—N9—C1121.55 (16)C10—C4—C3115.34 (17)
C10—N9—C8123.57 (18)C4—C10—N9120.01 (18)
C1—N9—C8114.86 (17)C4—C10—C5120.91 (19)
N2—C1—N9118.75 (16)N9—C10—C5119.08 (18)
C11—O2—C3—N22.1 (3)O3—C7—C8—N972.6 (3)
C5—C6—C7—O360.6 (3)C8—N9—C10—C50.1 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3···O1i0.94 (4)1.78 (4)2.709 (3)168 (3)
C12—H12B···Cgii0.963.083.956 (3)153
C12—H12B···N9ii0.963.043.856 (4)144
C12—H12B···C1ii0.963.174.116 (4)168
C6—H61···Cgiii0.87 (3)3.21 (3)3.718 (3)120 (2)
C6—H61···C1iii0.87 (3)3.00 (3)3.745 (4)144 (2)
C6—H61···N2iii0.87 (3)3.22 (3)3.788 (4)125 (2)
C7—H7···Cgiii0.99 (2)3.11 (2)3.736 (3)123 (1)
C7—H7···C10iii0.99 (2)2.86 (2)3.655 (3)138 (2)
C7—H7···C4iii0.99 (2)2.91 (2)3.783 (4)148 (2)
Symmetry codes: (i) x+1/2, y+1/2, z+1; (ii) x+2, y1/2, z+3/2; (iii) x+1/2, y1/2, z+1.
 

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