6-Ethyl-5-fluoro-2-methoxy­pyrimidin-4(3H)-one

Ye, Y.-Y.; Yang, K.

doi:10.1107/S1600536809035430

organic compounds

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ISSN: 2056-9890

Volume 65| Part 10| October 2009| Page o2582

doi:10.1107/S1600536809035430

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6-Ethyl-5-fluoro-2-methoxypyrimidin-4(3H)-one

Yu-Yuan Ye ^a ^* and Kai Yang ^b

^aSchool of Life Science and Pharmaceutical and Chemical Engineering, Taizhou University, Linhai 317000, People's Republic of China, and ^bCollege of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China
^*Correspondence e-mail: yeyuyuan@163.com

(Received 23 August 2009; accepted 2 September 2009; online 30 September 2009)

In the title compound, C₇H₉FN₂O₂, the methoxy and ethyl groups form dihedral angles of 1.4 (2) and 73.5 (3)°, respectively, with the mean plane of the pyrimidine ring. In the crystal structure, two molecules are linked by a pair of N—H⋯O hydrogen bonds, forming a centrosymmetric dimer.

Related literature

For fluoro-containing pyrimidines as intermediates for the synthesis of some anticancer and antifungal drugs, see: Bergmann et al. (1959 ); Butters et al. (2001 ).

Experimental

Crystal data

C₇H₉FN₂O₂
M_r = 172.16
Triclinic, $[P \overline 1]$
a = 4.5711 (4) Å
b = 8.4985 (8) Å
c = 10.8546 (11) Å
α = 88.043 (2)°
β = 79.737 (3)°
γ = 79.616 (2)°
V = 408.13 (7) Å³
Z = 2
Mo Kα radiation
μ = 0.12 mm⁻¹
T = 296 K
0.40 × 0.28 × 0.18 mm

Data collection

Rigaku R-AXIS RAPID diffractometer
Absorption correction: multi-scan (ABSCOR; Higashi, 1995 ) T_min = 0.948, T_max = 0.979
4010 measured reflections
1842 independent reflections
945 reflections with I > 2σ(I)
R_int = 0.019

Refinement

R[F² > 2σ(F²)] = 0.047
wR(F²) = 0.106
S = 1.00
1842 reflections
111 parameters
H-atom parameters constrained
Δρ_max = 0.39 e Å⁻³
Δρ_min = −0.37 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O2ⁱ	0.86	1.91	2.763 (2)	174
Symmetry code: (i) -x+1, -y+1, -z+1.

Data collection: PROCESS-AUTO (Rigaku/MSC, 2004 ); cell refinement: PROCESS-AUTO; data reduction: CrystalStructure (Rigaku/MSC, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997 ); software used to prepare material for publication: CrystalStructure (Rigaku/MSC, 2004).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809035430/is2454sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809035430/is2454Isup2.hkl

checkCIF report

Comment top

The fluoro-containing pyrimidines have been used as a kind of important intermediates for the synthesis of some anticancer drugs and antifungal drugs (Bergmann et al., 1959; Butters et al., 2001). In the synthesis of the novel antifungal drug-Voriconazole, we have prepared the title compound 6-ethyl-5-fluoro-2-methoxypyrimidin-4(3H)-one as an intermediate, which was synthesized by reacting methyl 2-fluoro-3-oxopentanoate with o-methylisourea sulfate in a solution of sodium methylate in methanol.

The molecular structure of the title compound, (I), is illustrated in Fig. 1. The bond lenghth of C4—O2 and C1—O1 are 1.238 (3) and 1.321 (2) Å, respectively, corresponding to a double C=O bond and a Csp²—O single bond. In the six-membered pyrimidine ring, the even bond lengths of C—N and C—C are 1.361 (3) and 1.380 (3) Å, respectively, indicating these bond forming a conjugating system. The atoms in the pyrimidine ring (C1–C4/N1/N2) form a good plane with a mean deviation of 0.006 Å. An intermolecular N—H···O hydrogen bond was found to link two molecules as a pair (Fig. 2 and Table 1).

Related literature top

For fluoro-containing pyrimidines as intermediates for the synthesis of some anticancer and antifungal drugs, see: Bergmann et al. (1959); Butters et al. (2001).

Experimental top

To a 250 ml flask was added a 80 ml solution of 25% sodium methylate in methanol. The solution was cooled to 278 K, and then 40 g o-methylisourea sulfate and 20 g methyl 2-fluoro-3-oxopentanoate were added. After the addition, the mixture were stirred at 298 K for half an hour and refluxed for three hours. The mixture was concentrated under reduced pressure, and the residue was dissolved with 200 ml water. The aqueous solution was treated with 6M hydrochloric acid to pH3 and cooled in refrigerator for three hours. The resulted precipitate was filtered, to give 12.5 g product as white powder (yield 53.8%; m.p. 447–449 K). Since the product was not found to be suitable for X-ray diffraction studies, a few samples were dissolved in absolute ethanol, which was allowed to evaporate slowly to give colourless crystals of (I) suitable for X-ray diffraction studies.

Computing details top

Data collection: PROCESS-AUTO (Rigaku/MSC, 2004); cell refinement: PROCESS-AUTO (Rigaku/MSC, 2004); data reduction: CrystalStructure (Rigaku/MSC, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: CrystalStructure (Rigaku/MSC, 2004).

Figures top

	Fig. 1. The molecular structure of (I) with 30% probability displacement ellipsoids.
	Fig. 2. Packing diagram of (I), showing hydrogen bonds as dashed lines.

6-Ethyl-5-fluoro-2-methoxypyrimidin-4(3H)-one top

Crystal data top

C₇H₉FN₂O₂	Z = 2
M_r = 172.16	F(000) = 180.00
Triclinic, P1	D_x = 1.401 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71075 Å
a = 4.5711 (4) Å	Cell parameters from 2411 reflections
b = 8.4985 (8) Å	θ = 3.1–27.4°
c = 10.8546 (11) Å	µ = 0.12 mm⁻¹
α = 88.043 (2)°	T = 296 K
β = 79.737 (3)°	Chunk, colorless
γ = 79.616 (2)°	0.40 × 0.28 × 0.18 mm
V = 408.13 (7) Å³

Data collection top

Rigaku R-AXIS RAPID diffractometer	945 reflections with I > 2σ(I)
Detector resolution: 10.00 pixels mm^-1	R_int = 0.019
ω scans	θ_max = 27.4°
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)	h = −5→5
T_min = 0.948, T_max = 0.979	k = −10→11
4010 measured reflections	l = −14→14
1842 independent reflections

Refinement top

Refinement on F²	w = 1/[σ²(F_o²) + (0.P)² + 0.345P] where P = (F_o² + 2F_c²)/3
R[F² > 2σ(F²)] = 0.047	(Δ/σ)_max < 0.001
wR(F²) = 0.106	Δρ_max = 0.39 e Å⁻³
S = 1.00	Δρ_min = −0.37 e Å⁻³
1842 reflections	Extinction correction: SHELXL97 (Sheldrick, 2008)
111 parameters	Extinction coefficient: 0.025 (2)
H-atom parameters constrained

Crystal data top

C₇H₉FN₂O₂	γ = 79.616 (2)°
M_r = 172.16	V = 408.13 (7) Å³
Triclinic, P1	Z = 2
a = 4.5711 (4) Å	Mo Kα radiation
b = 8.4985 (8) Å	µ = 0.12 mm⁻¹
c = 10.8546 (11) Å	T = 296 K
α = 88.043 (2)°	0.40 × 0.28 × 0.18 mm
β = 79.737 (3)°

Data collection top

Rigaku R-AXIS RAPID diffractometer	1842 independent reflections
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)	945 reflections with I > 2σ(I)
T_min = 0.948, T_max = 0.979	R_int = 0.019
4010 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.047	111 parameters
wR(F²) = 0.106	H-atom parameters constrained
S = 1.00	Δρ_max = 0.39 e Å⁻³
1842 reflections	Δρ_min = −0.37 e Å⁻³

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 using all reflections. The weighted R-factor (wR) and goodness of fit (S) are based on F². R-factor (gt) are based on F. The threshold expression of F² > 2.0 σ(F²) is used only for calculating R-factor (gt).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
F1	−0.2750 (3)	0.5521 (2)	0.78974 (17)	0.0840 (5)
O1	0.6346 (4)	0.0891 (2)	0.60826 (17)	0.0674 (5)
O2	0.1625 (4)	0.6002 (2)	0.58950 (19)	0.0754 (6)
N1	0.3901 (4)	0.3399 (2)	0.6042 (2)	0.0577 (5)
N2	0.2058 (4)	0.1623 (2)	0.7615 (2)	0.0587 (5)
C1	0.4039 (5)	0.1970 (2)	0.6603 (2)	0.0558 (6)
C2	−0.0212 (5)	0.2877 (3)	0.8040 (2)	0.0579 (6)
C3	−0.0446 (5)	0.4310 (3)	0.7475 (2)	0.0590 (7)
C4	0.1656 (6)	0.4689 (3)	0.6427 (2)	0.0603 (7)
C5	0.6683 (7)	−0.0711 (2)	0.6608 (2)	0.0788 (9)
C6	−0.2321 (6)	0.2513 (3)	0.9191 (2)	0.0753 (8)
C7	−0.0903 (8)	0.2402 (4)	1.0339 (2)	0.0997 (11)
H1	0.5276	0.3520	0.5412	0.069*
H51	0.7001	−0.0670	0.7457	0.095*
H52	0.8384	−0.1380	0.6122	0.095*
H53	0.4886	−0.1142	0.6595	0.095*
H61	−0.2930	0.1500	0.9075	0.090*
H62	−0.4085	0.3355	0.9311	0.090*
H71	0.0851	0.1573	1.0231	0.120*
H72	−0.2328	0.2156	1.1050	0.120*
H73	−0.0324	0.3405	1.0473	0.120*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0660 (10)	0.0684 (10)	0.1026 (13)	0.0173 (8)	−0.0007 (9)	−0.0156 (9)
O1	0.0774 (13)	0.0441 (9)	0.0690 (12)	0.0153 (9)	−0.0074 (10)	−0.0028 (8)
O2	0.0822 (14)	0.0447 (10)	0.0864 (14)	0.0146 (9)	−0.0062 (11)	0.0003 (9)
N1	0.0625 (13)	0.0437 (11)	0.0595 (13)	0.0091 (10)	−0.0095 (10)	−0.0023 (10)
N2	0.0594 (13)	0.0517 (12)	0.0629 (14)	−0.0013 (10)	−0.0131 (11)	−0.0034 (10)
C1	0.0606 (16)	0.0431 (13)	0.0625 (16)	0.0074 (11)	−0.0230 (13)	−0.0094 (12)
C2	0.0502 (15)	0.0603 (16)	0.0623 (16)	−0.0031 (12)	−0.0122 (12)	−0.0101 (13)
C3	0.0499 (15)	0.0520 (15)	0.0694 (17)	0.0079 (12)	−0.0097 (13)	−0.0117 (13)
C4	0.0620 (17)	0.0456 (14)	0.0698 (17)	0.0082 (12)	−0.0187 (14)	−0.0083 (13)
C5	0.102 (2)	0.0428 (14)	0.082 (2)	0.0155 (15)	−0.0193 (18)	−0.0009 (14)
C6	0.0602 (18)	0.077 (2)	0.085 (2)	−0.0112 (15)	−0.0033 (16)	−0.0051 (17)
C7	0.091 (2)	0.136 (3)	0.069 (2)	−0.029 (2)	0.0017 (18)	0.004 (2)

Geometric parameters (Å, º) top

F1—C3	1.359 (2)	C6—C7	1.496 (4)
O1—C1	1.321 (2)	N1—H1	0.860
O1—C5	1.451 (3)	C5—H51	0.960
O2—C4	1.238 (3)	C5—H52	0.960
N1—C1	1.336 (3)	C5—H53	0.960
N1—C4	1.379 (3)	C6—H61	0.970
N2—C1	1.354 (3)	C6—H62	0.970
N2—C2	1.375 (3)	C7—H71	0.960
C2—C3	1.340 (3)	C7—H72	0.960
C2—C6	1.496 (3)	C7—H73	0.960
C3—C4	1.420 (3)

C1—O1—C5	118.15 (19)	O1—C5—H51	109.5
C1—N1—C4	123.1 (2)	O1—C5—H52	109.5
C1—N2—C2	114.5 (2)	O1—C5—H53	109.5
O1—C1—N1	113.63 (19)	H51—C5—H52	109.5
O1—C1—N2	121.8 (2)	H51—C5—H53	109.5
N1—C1—N2	124.6 (2)	H52—C5—H53	109.5
N2—C2—C3	122.1 (2)	C2—C6—H61	108.7
N2—C2—C6	114.4 (2)	C2—C6—H62	108.7
C3—C2—C6	123.5 (2)	C7—C6—H61	108.7
F1—C3—C2	121.0 (2)	C7—C6—H62	108.7
F1—C3—C4	115.4 (2)	H61—C6—H62	109.5
C2—C3—C4	123.6 (2)	C6—C7—H71	109.5
O2—C4—N1	121.3 (2)	C6—C7—H72	109.5
O2—C4—C3	126.6 (2)	C6—C7—H73	109.5
N1—C4—C3	112.1 (2)	H71—C7—H72	109.5
C2—C6—C7	112.5 (2)	H71—C7—H73	109.5
C1—N1—H1	118.5	H72—C7—H73	109.5
C4—N1—H1	118.5

C5—O1—C1—N1	−179.1 (2)	N2—C2—C3—F1	178.6 (2)
C5—O1—C1—N2	1.4 (3)	N2—C2—C3—C4	−2.4 (4)
C1—N1—C4—O2	179.0 (2)	N2—C2—C6—C7	72.7 (3)
C1—N1—C4—C3	−0.0 (3)	C3—C2—C6—C7	−105.8 (3)
C4—N1—C1—O1	179.3 (2)	C6—C2—C3—F1	−3.0 (4)
C4—N1—C1—N2	−1.2 (4)	C6—C2—C3—C4	176.0 (3)
C1—N2—C2—C3	1.1 (4)	F1—C3—C4—O2	1.9 (4)
C1—N2—C2—C6	−177.5 (2)	F1—C3—C4—N1	−179.2 (2)
C2—N2—C1—O1	−179.9 (2)	C2—C3—C4—O2	−177.2 (3)
C2—N2—C1—N1	0.6 (4)	C2—C3—C4—N1	1.8 (4)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O2ⁱ	0.86	1.91	2.763 (2)	174

Symmetry code: (i) −x+1, −y+1, −z+1.

Experimental details

Crystal data
Chemical formula	C₇H₉FN₂O₂
M_r	172.16
Crystal system, space group	Triclinic, P1
Temperature (K)	296
a, b, c (Å)	4.5711 (4), 8.4985 (8), 10.8546 (11)
α, β, γ (°)	88.043 (2), 79.737 (3), 79.616 (2)
V (Å³)	408.13 (7)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.12
Crystal size (mm)	0.40 × 0.28 × 0.18

Data collection
Diffractometer	Rigaku R-AXIS RAPID diffractometer
Absorption correction	Multi-scan (ABSCOR; Higashi, 1995)
T_min, T_max	0.948, 0.979
No. of measured, independent and observed [I > 2σ(I)] reflections	4010, 1842, 945
R_int	0.019
(sin θ/λ)_max (Å⁻¹)	0.648

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.047, 0.106, 1.00
No. of reflections	1842
No. of parameters	111
No. of restraints	?
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.39, −0.37

Computer programs: PROCESS-AUTO (Rigaku/MSC, 2004), CrystalStructure (Rigaku/MSC, 2004), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 (Farrugia, 1997).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O2ⁱ	0.86	1.907	2.763 (2)	174

Symmetry code: (i) −x+1, −y+1, −z+1.

Acknowledgements

The authors acknowledge support from the Educational Commission of Zhejiang Province (200803289).

References

Bergmann, E. D., Cohen, S. & Shahak, I. (1959). J. Chem. Soc. 11, 3278–3285. CrossRef Web of Science Google Scholar
Butters, M., Ebbs, J., Green, S. P., MacRae, J., Morland, M. C., Murtiashaw, C. W. & Pettman, A. J. (2001). Org. Process Res. Dev. 5, 28–36. Web of Science CrossRef CAS Google Scholar
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565. CrossRef IUCr Journals Google Scholar
Higashi, T. (1995). ABSCOR. Rigaku Corporation, Tokyo, Japan. Google Scholar
Rigaku/MSC (2004). PROCESS-AUTO and CrystalStructure. Rigaku/MSC, The Woodlands, Texas, USA. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar