6-Methyl­sulfanyl-4H-pyrimido[1,6-a]pyrimidin-4-one

Huang, Q.; Richardson, P.F.; Rui, E.; Rheingold, A.L.; Yanovsky, A.

doi:10.1107/S1600536809038562

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 65| Part 10| October 2009| Page o2572

doi:10.1107/S1600536809038562

Open

access

6-Methylsulfanyl-4H-pyrimido[1,6-a]pyrimidin-4-one

Quinhua Huang,^a Paul F. Richardson,^a Eugene Rui,^a Arnold L. Rheingold ^b and Alex Yanovsky ^a ^*

^aPfizer Global Research and Development, La Jolla Labs, 10770 Science Center Drive, San Diego, CA 92121, USA, and ^bDepartment of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
^*Correspondence e-mail: alex.yanovsky@pfizer.com

(Received 18 September 2009; accepted 23 September 2009; online 30 September 2009)

Reaction of 2-(methylsulfanyl)pyrimidin-4-amine with the 5-(methoxyvinylidene) derivative of Meldrum's acid and subsequent heating of the product in Dowtherm fluid yielded the title compound, C₈H₇N₃OS, which was proven to contain a bicyclic 4H-pyrimido[1,6-a]pyrimidine system. All non-H atoms of the molecule are coplanar within 0.15 Å. The bond-length distribution in the bicyclic core shows localization of the double bonds. The geometry of the intramolecular S⋯O 1,5-contact [2.534 (2) Å] is consistent with the existence of an attractive interaction.

Related literature

For the structure of a compound with a similar bicyclic carbon–nitrogen core, see: Olomucki et al. (1984 ). For statistical studies of the geometry of S⋯O interactions, see: Rosenfield et al. (1977 ); Iwaoka et al. (2002 ).

Experimental

Crystal data

C₈H₇N₃OS
M_r = 193.23
Monoclinic, P 2₁ /c
a = 9.7621 (8) Å
b = 4.1725 (3) Å
c = 20.4092 (16) Å
β = 100.106 (1)°
V = 818.42 (11) Å³
Z = 4
Mo Kα radiation
μ = 0.35 mm⁻¹
T = 123 K
0.48 × 0.14 × 0.08 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2001 ) T_min = 0.849, T_max = 0.972
6497 measured reflections
1498 independent reflections
1333 reflections with I > 2σ(I)
R_int = 0.022

Refinement

R[F² > 2σ(F²)] = 0.035
wR(F²) = 0.097
S = 1.13
1498 reflections
118 parameters
H-atom parameters constrained
Δρ_max = 0.43 e Å⁻³
Δρ_min = −0.19 e Å⁻³

Data collection: APEX2 (Bruker, 2004 ); cell refinement: SAINT (Bruker, 2004); data reduction: SAINT; program(s) used to solve structure: SIR2004 (Burla et al., 2005 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ); molecular graphics: ORTEP-32 (Farrugia, 1997 ); software used to prepare material for publication: WinGX (Farrugia, 1999 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809038562/rz2363sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809038562/rz2363Isup2.hkl

checkCIF report

Comment top

The title compound was obtained by reaction of 2-(methylsulfanyl)pyrimidin-4-amine with 5-(methoxyvinylidene) derivative of Meldrum's acid and subsequent heating of the product in Dowtherm fluid (Fig. 1).

All non-hydrogen atoms of the molecule of the title compound (Fig. 2) are approximately coplanar; maximum deviation of the C1 atom from the least-squares plane is 0.143 (2) Å. The bond length values indicate localization of double bonds in the bicyclic core (N1–C2, 1.298 (3) Å; N3–C5, 1.308 (3) Å; C3–C4, 1.351 (3) Å; C6–C7, 1.355 (3) Å;), which is consistent with the fact that no resonance structures can be drawn. Surprisingly, to the best of our knowledge no other isolated bicyclic carbon-nitrogen system with the same positions of the N atoms was structurally studied. Similar bond lengths were observed in dihydropyrimido(1,2 - c)purine derivative, where analogous bicyclic core makes up a part of the tricyclic system (Olomucki et al., 1984).

The S1···O1 distance [2.534 (2) Å] and the O1···S1—C1 angle [177.5 (1)°] are consistent with the existence of the intramolecular attractive interaction (Rosenfield et al., 1977; Iwaoka et al., 2002).

Related literature top

For the structure of a compound with a similar bicyclic carbon–nitrogen core, see: Olomucki et al. (1984). For statistical studies of the geometry of S···O interactions, see: Rosenfield et al. (1977); Iwaoka et al. (2002).

Experimental top

A mixture of (2-methylsulfanyl)pyrimidin-4-ylamine (5.0 g, 35 mmol, 1.0 eq), 5-(methoxyvinylidene) derivative of Meldrum's acid (9.23 g, 49.6 mmol, 1.4 eq), and 2-PrOH (100 ml) was refluxed at 85°C for 1 h to reach reaction completion. The resulting suspension was cooled to 25°C, filtered, and washed with EtOH to afford 10 g of the displacement product as a yellow solid in 96% yield. LC—MS (APCI, M+1) 296.0; ¹H NMR (400 MHz, DMSO-d₆) δ p.p.m. 1.69 (s, 6 H) 2.55 (s, 3 H) 7.43 (d, J = 5.54 Hz, 1 H) 8.57 (d, J = 5.54 Hz, 1 H) 9.20 (s, 1 H) 11.35 (s, 1 H).

The generated 5-[(2-methylsulfanyl)pyrimidin-4-ylaminovinylidene] derivative of Meldrum's acid (6.5 g, 22 mmol, 1.0 eq) was added portionwise to 130 ml of preheated Dowtherm A at 220°C (inner temperature). After being reacted at 220°C for 10 min, LC—MS indicated that reaction was complete. The reaction mixture was cooled to 25°C and diluted with 1 L heptane. The resulting suspension was left to stand overnight. The solid was filtered, washed with heptane, and dried under vacuum to afford 3.4 g of the target compound as a yellow solid in (80% yield). LC—MS (APCI, M+1) 194.0; ¹H NMR (400 MHz, DMSO-d₆) δ p.p.m. 2.40 (s, 3 H) 6.35 (d, J = 6.55 Hz, 1 H) 7.04 (d, J = 6.29 Hz, 1 H) 8.08 (t, J = 6.55 Hz, 2 H). The product was recrystallized from EtOAc/hexane to yield single crystals suitable for X-ray diffraction studies.

Computing details top

Data collection: APEX2 (Bruker, 2004); cell refinement: SAINT (Bruker, 2004); data reduction: SAINT (Bruker, 2004); program(s) used to solve structure: SIR2004 (Burla et al., 2005); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-32 (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top

	Fig. 1. Synthesis of the title compound.
	Fig. 2. Molecular structure of the title compound, showing 50% probability displacement ellipsoids and atom numbering scheme. H atoms are drawn as circles with arbitrary small radius.

6-Methylsulfanyl-4H-pyrimido[1,6-a]pyrimidin-4-one top

Crystal data top

C₈H₇N₃OS	F(000) = 400
M_r = 193.23	D_x = 1.568 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 4134 reflections
a = 9.7621 (8) Å	θ = 3.2–25.4°
b = 4.1725 (3) Å	µ = 0.35 mm⁻¹
c = 20.4092 (16) Å	T = 123 K
β = 100.106 (1)°	Blade, brown
V = 818.42 (11) Å³	0.48 × 0.14 × 0.08 mm
Z = 4

Data collection top

Bruker APEXII CCD diffractometer	1498 independent reflections
Radiation source: fine-focus sealed tube	1333 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.022
ϕ and ω scans	θ_max = 25.4°, θ_min = 2.1°
Absorption correction: multi-scan (SADABS; Bruker, 2001)	h = −11→11
T_min = 0.849, T_max = 0.972	k = −4→5
6497 measured reflections	l = −24→24

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.035	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.097	H-atom parameters constrained
S = 1.13	w = 1/[σ²(F_o²) + (0.045P)² + 0.5615P] where P = (F_o² + 2F_c²)/3
1498 reflections	(Δ/σ)_max = 0.001
118 parameters	Δρ_max = 0.43 e Å⁻³
0 restraints	Δρ_min = −0.19 e Å⁻³

Crystal data top

C₈H₇N₃OS	V = 818.42 (11) Å³
M_r = 193.23	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 9.7621 (8) Å	µ = 0.35 mm⁻¹
b = 4.1725 (3) Å	T = 123 K
c = 20.4092 (16) Å	0.48 × 0.14 × 0.08 mm
β = 100.106 (1)°

Data collection top

Bruker APEXII CCD diffractometer	1498 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2001)	1333 reflections with I > 2σ(I)
T_min = 0.849, T_max = 0.972	R_int = 0.022
6497 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.035	0 restraints
wR(F²) = 0.097	H-atom parameters constrained
S = 1.13	Δρ_max = 0.43 e Å⁻³
1498 reflections	Δρ_min = −0.19 e Å⁻³
118 parameters

Special details top

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

	x	y	z	U_iso*/U_eq
S1	0.56563 (5)	0.91748 (12)	0.81678 (2)	0.02069 (19)
O1	0.80408 (15)	0.9008 (4)	0.78390 (7)	0.0276 (4)
N1	0.59517 (17)	0.5753 (4)	0.92701 (8)	0.0203 (4)
N2	0.79659 (16)	0.5851 (4)	0.87620 (7)	0.0172 (4)
N3	0.99408 (17)	0.2689 (4)	0.92351 (8)	0.0238 (4)
C1	0.3990 (2)	0.9169 (5)	0.84302 (11)	0.0280 (5)
H1A	0.3333	1.0474	0.8123	0.042*
H1B	0.4089	1.0064	0.8880	0.042*
H1C	0.3642	0.6966	0.8431	0.042*
C2	0.65797 (19)	0.6714 (5)	0.87950 (9)	0.0183 (4)
C3	0.6652 (2)	0.3762 (5)	0.97497 (10)	0.0209 (4)
H3B	0.6193	0.3094	1.0100	0.025*
C4	0.7959 (2)	0.2700 (5)	0.97507 (9)	0.0203 (4)
H4A	0.8392	0.1284	1.0089	0.024*
C5	0.8678 (2)	0.3717 (5)	0.92427 (9)	0.0186 (4)
C6	1.0583 (2)	0.3766 (5)	0.87347 (11)	0.0254 (5)
H6A	1.1495	0.3010	0.8719	0.030*
C7	0.9993 (2)	0.5853 (5)	0.82589 (9)	0.0199 (4)
H7A	1.0506	0.6512	0.7927	0.024*
C8	0.8652 (2)	0.7063 (5)	0.82424 (9)	0.0219 (4)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0177 (3)	0.0225 (3)	0.0219 (3)	0.00111 (19)	0.0038 (2)	0.0028 (2)
O1	0.0237 (8)	0.0363 (9)	0.0241 (7)	0.0002 (7)	0.0079 (6)	0.0095 (7)
N1	0.0196 (8)	0.0199 (9)	0.0220 (8)	−0.0009 (7)	0.0053 (7)	−0.0002 (7)
N2	0.0184 (8)	0.0176 (8)	0.0164 (8)	−0.0021 (6)	0.0050 (6)	−0.0017 (6)
N3	0.0199 (8)	0.0240 (9)	0.0278 (9)	0.0015 (7)	0.0047 (7)	−0.0014 (8)
C1	0.0201 (11)	0.0335 (12)	0.0312 (11)	0.0032 (9)	0.0068 (9)	0.0059 (10)
C2	0.0169 (9)	0.0178 (9)	0.0201 (10)	−0.0015 (8)	0.0026 (8)	−0.0037 (8)
C3	0.0211 (10)	0.0232 (10)	0.0190 (10)	−0.0025 (8)	0.0052 (8)	0.0004 (8)
C4	0.0233 (10)	0.0189 (10)	0.0184 (10)	−0.0007 (8)	0.0026 (8)	0.0006 (8)
C5	0.0179 (10)	0.0173 (9)	0.0200 (10)	−0.0016 (8)	0.0022 (8)	−0.0041 (8)
C6	0.0180 (10)	0.0264 (11)	0.0326 (11)	−0.0005 (9)	0.0068 (9)	−0.0070 (9)
C7	0.0253 (11)	0.0186 (10)	0.0183 (10)	−0.0042 (8)	0.0108 (8)	−0.0040 (8)
C8	0.0234 (10)	0.0245 (11)	0.0186 (10)	−0.0066 (9)	0.0059 (8)	−0.0026 (9)

Geometric parameters (Å, º) top

S1—C2	1.761 (2)	C1—H1B	0.9800
S1—C1	1.799 (2)	C1—H1C	0.9800
O1—C8	1.233 (2)	C3—C4	1.351 (3)
N1—C2	1.298 (3)	C3—H3B	0.9500
N1—C3	1.371 (3)	C4—C5	1.415 (3)
N2—C2	1.413 (2)	C4—H4A	0.9500
N2—C5	1.414 (2)	C6—C7	1.355 (3)
N2—C8	1.442 (2)	C6—H6A	0.9500
N3—C5	1.308 (3)	C7—C8	1.398 (3)
N3—C6	1.365 (3)	C7—H7A	0.9500
C1—H1A	0.9800

C2—S1—C1	99.03 (9)	N1—C3—H3B	118.2
C2—N1—C3	118.60 (17)	C3—C4—C5	119.37 (18)
C2—N2—C5	119.08 (16)	C3—C4—H4A	120.3
C2—N2—C8	121.20 (16)	C5—C4—H4A	120.3
C5—N2—C8	119.70 (16)	N3—C5—N2	123.26 (18)
C5—N3—C6	117.29 (18)	N3—C5—C4	119.98 (18)
S1—C1—H1A	109.5	N2—C5—C4	116.76 (17)
S1—C1—H1B	109.5	C7—C6—N3	123.66 (19)
H1A—C1—H1B	109.5	C7—C6—H6A	118.2
S1—C1—H1C	109.5	N3—C6—H6A	118.2
H1A—C1—H1C	109.5	C6—C7—C8	121.85 (18)
H1B—C1—H1C	109.5	C6—C7—H7A	119.1
N1—C2—N2	122.57 (17)	C8—C7—H7A	119.1
N1—C2—S1	118.33 (15)	O1—C8—C7	126.55 (18)
N2—C2—S1	119.10 (14)	O1—C8—N2	119.26 (18)
C4—C3—N1	123.53 (18)	C7—C8—N2	114.19 (17)
C4—C3—H3B	118.2

Experimental details

Crystal data
Chemical formula	C₈H₇N₃OS
M_r	193.23
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	123
a, b, c (Å)	9.7621 (8), 4.1725 (3), 20.4092 (16)
β (°)	100.106 (1)
V (Å³)	818.42 (11)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.35
Crystal size (mm)	0.48 × 0.14 × 0.08

Data collection
Diffractometer	Bruker APEXII CCD diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2001)
T_min, T_max	0.849, 0.972
No. of measured, independent and observed [I > 2σ(I)] reflections	6497, 1498, 1333
R_int	0.022
(sin θ/λ)_max (Å⁻¹)	0.604

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.035, 0.097, 1.13
No. of reflections	1498
No. of parameters	118
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.43, −0.19

Computer programs: APEX2 (Bruker, 2004), SAINT (Bruker, 2004), SIR2004 (Burla et al., 2005), SHELXL97 (Sheldrick, 2008), ORTEP-32 (Farrugia, 1997), WinGX (Farrugia, 1999).

References

Bruker (2001). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Bruker (2004). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Burla, M. C., Caliandro, R., Camalli, M., Carrozzini, B., Cascarano, G. L., De Caro, L., Giacovazzo, C., Polidori, G. & Spagna, R. (2005). J. Appl. Cryst. 38, 381–388. Web of Science CrossRef CAS IUCr Journals Google Scholar
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565. CrossRef IUCr Journals Google Scholar
Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838. CrossRef CAS IUCr Journals Google Scholar
Iwaoka, M., Takemoto, S. & Tomoda, S. (2002). J. Am. Chem. Soc. 124, 10613–10620. Web of Science CrossRef PubMed CAS Google Scholar
Olomucki, M., Le Gall, J. Y., Colinart, S., Durant, F., Norberg, B. & Evrard, G. (1984). Tetrahedron Lett. 25, 3471–3474. CSD CrossRef CAS Web of Science Google Scholar
Rosenfield, R. E. Jr, Parthasarathy, R. & Dunitz, J. D. (1977). J. Am. Chem. Soc. 99, 4860–4862. CrossRef CAS Web of Science Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar