Ethyl 3-(4-fluoro-phen-yl)-6-methyl-4-oxo-2-(1-cyclohexylamino)-3,4-dihydro-furo[2,3-d]pyrimidine-5-carboxyl-ate.

In the crystal structure of the title compound, C(22)H(24)FN(3)O(4), the two fused rings of furo[2,3-d]pyrimidine form a dihedral angle of 0.88 (13)°. The attached benzene ring is twisted with respect to the heterocyclic pyrimidinone ring, making a dihedral angle of 75.07 (12)°. The cyclo-hexyl ring shows a distorted chair conformation. The mol-ecular structure is stabilized by intra-molecular C-H⋯O and C-H⋯N hydrogen-bonding inter-actions. The crystal packing is mainly stabilized by C-H⋯π hydrogen-bond inter-actions. Further stability is provided by C-F⋯π and C-O⋯π stacking inter-actions.

Related literature

The preparation and biological activity are described by Miyazaki et al. (2007 ▶), Gangjee et al. (2006 ▶) and Lagu et al. (2000 ▶). For related literature, see: Ding et al. (2004 ▶). For the crystal structure of another fused pyrimidinone derivative, see: Hu et al. (2007 ▶).

Experimental

Crystal data

C22H24FN3O4

M = 413.44

Triclinic,

a = 9.2051 (8) Å

b = 10.7957 (9) Å

c = 11.6601 (10) Å

α = 106.681 (1)°

β = 100.417 (2)°

γ = 101.550 (2)°

V = 1051.85 (16) Å3

Z = 2

Mo Kα radiation

μ = 0.10 mm−1

T = 291 (2) K

0.30 × 0.30 × 0.20 mm

Data collection

Bruker SMART 4K CCD area-detector diffractometer

Absorption correction: multi-scan (SADABS; Sheldrick, 2003 ▶) T min = 0.972, T max = 0.981

10785 measured reflections

4505 independent reflections

2941 reflections with I > 2σ(I)

R int = 0.036

Refinement

R[F 2 > 2σ(F 2)] = 0.066

wR(F 2) = 0.182

S = 1.09

4505 reflections

276 parameters

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.27 e Å−3

Δρmin = −0.21 e Å−3

Data collection: SMART (Bruker, 2001 ▶); cell refinement: SAINT-Plus (Bruker, 2001 ▶); data reduction: SAINT-Plus; 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: SHELXTL (Sheldrick, 2001 ▶).

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536807066780/at2523sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536807066780/at2523Isup2.hkl

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

C22H24FN3O4	Z = 2
Mr = 413.44	F000 = 436
Triclinic, P1	Dx = 1.305 Mg m−3
Hall symbol: -P 1	Mo Kα radiation λ = 0.71073 Å
a = 9.2051 (8) Å	Cell parameters from 1930 reflections
b = 10.7957 (9) Å	θ = 2.3–22.7º
c = 11.6601 (10) Å	µ = 0.10 mm−1
α = 106.681 (1)º	T = 291 (2) K
β = 100.417 (2)º	Block, colourless
γ = 101.550 (2)º	0.30 × 0.30 × 0.20 mm
V = 1051.85 (16) Å3

Bruker SMART 4K CCD area-detector diffractometer	4505 independent reflections
Radiation source: fine-focus sealed tube	2941 reflections with I > 2σ(I)
Monochromator: graphite	Rint = 0.036
T = 291(2) K	θmax = 27.0º
φ and ω scans	θmin = 1.9º
Absorption correction: multi-scan(SADABS; Sheldrick, 2003)	h = −11→11
Tmin = 0.972, Tmax = 0.981	k = −13→13
10785 measured reflections	l = −14→14

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)] = 0.066	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.182	w = 1/[σ2(Fo2) + (0.084P)2 + 0.0618P] where P = (Fo2 + 2Fc2)/3
S = 1.09	(Δ/σ)max = 0.001
4505 reflections	Δρmax = 0.27 e Å−3
276 parameters	Δρmin = −0.20 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
C1	0.3069 (4)	1.3641 (3)	0.4580 (4)	0.0893 (11)
H1A	0.2011	1.3243	0.4505	0.134*
H1B	0.3160	1.4451	0.4379	0.134*
H1C	0.3651	1.3846	0.5413	0.134*
C2	0.3654 (4)	1.2701 (3)	0.3728 (3)	0.0611 (8)
H2A	0.3083	1.2498	0.2881	0.073*
H2B	0.4726	1.3091	0.3800	0.073*
C3	0.3773 (3)	1.0444 (2)	0.3310 (2)	0.0405 (6)
C4	0.3423 (3)	0.9266 (2)	0.37091 (19)	0.0382 (5)
C5	0.3652 (3)	0.8068 (3)	0.3117 (2)	0.0436 (6)
C6	0.4214 (4)	0.7543 (3)	0.2014 (2)	0.0621 (8)
H6A	0.4101	0.8081	0.1494	0.093*
H6B	0.3631	0.6632	0.1563	0.093*
H6C	0.5276	0.7573	0.2269	0.093*
C7	0.2826 (2)	0.9094 (2)	0.47482 (18)	0.0346 (5)
C8	0.2770 (3)	0.7808 (2)	0.46902 (19)	0.0388 (5)
C9	0.2328 (3)	0.9897 (2)	0.5730 (2)	0.0404 (6)
C10	0.1892 (3)	0.7846 (2)	0.6342 (2)	0.0402 (6)
C11	0.1584 (3)	0.9935 (2)	0.76523 (19)	0.0372 (5)
C12	0.0208 (3)	1.0263 (2)	0.7601 (2)	0.0433 (6)
H12	−0.0514	1.0000	0.6847	0.052*
C13	−0.0090 (3)	1.0983 (3)	0.8672 (2)	0.0486 (6)
H13	−0.1013	1.1213	0.8653	0.058*
C14	0.0991 (3)	1.1353 (2)	0.9765 (2)	0.0480 (6)
C15	0.2366 (3)	1.1045 (3)	0.9847 (2)	0.0512 (7)
H15	0.3080	1.1311	1.0605	0.061*
C16	0.2661 (3)	1.0329 (2)	0.8772 (2)	0.0442 (6)
H16	0.3591	1.0110	0.8798	0.053*
C17	0.1711 (3)	0.6040 (2)	0.7262 (2)	0.0482 (6)
H17	0.1861	0.5517	0.6475	0.058*
C18	0.0384 (3)	0.5200 (3)	0.7535 (3)	0.0711 (9)
H18A	−0.0525	0.4956	0.6862	0.085*
H18B	0.0175	0.5719	0.8286	0.085*
C19	0.0750 (4)	0.3927 (3)	0.7692 (3)	0.0855 (11)
H19A	−0.0089	0.3431	0.7918	0.103*
H19B	0.0843	0.3362	0.6910	0.103*
C22	0.3165 (3)	0.6368 (3)	0.8250 (3)	0.0721 (9)
H22A	0.3063	0.6937	0.9027	0.087*
H22B	0.4009	0.6863	0.8028	0.087*
C21	0.3524 (4)	0.5105 (4)	0.8417 (4)	0.0887 (11)
H21A	0.3757	0.4594	0.7675	0.106*
H21B	0.4423	0.5356	0.9100	0.106*
F1	0.0682 (2)	1.20612 (17)	1.08220 (14)	0.0762 (5)
N1	0.1902 (2)	0.91680 (18)	0.65370 (16)	0.0378 (5)
N2	0.2326 (2)	0.71226 (19)	0.54199 (17)	0.0446 (5)
N3	0.1374 (3)	0.7269 (2)	0.71300 (19)	0.0498 (6)
H3	0.117 (3)	0.781 (3)	0.774 (2)	0.060*
O1	0.3480 (2)	1.14890 (17)	0.40502 (15)	0.0509 (5)
O2	0.4260 (2)	1.04606 (19)	0.24179 (15)	0.0588 (5)
O3	0.32637 (19)	0.71581 (16)	0.37123 (14)	0.0467 (4)
O4	0.2239 (2)	1.10393 (18)	0.59732 (17)	0.0639 (6)
C20	0.2211 (4)	0.4244 (3)	0.8669 (3)	0.0785 (10)
H20A	0.2073	0.4705	0.9472	0.094*
H20B	0.2447	0.3414	0.8694	0.094*

	U11	U22	U33	U12	U13	U23
C1	0.116 (3)	0.060 (2)	0.113 (3)	0.040 (2)	0.051 (2)	0.036 (2)
C2	0.078 (2)	0.0520 (18)	0.0698 (18)	0.0230 (15)	0.0288 (15)	0.0349 (15)
C3	0.0412 (13)	0.0461 (15)	0.0371 (12)	0.0116 (11)	0.0116 (10)	0.0170 (11)
C4	0.0408 (13)	0.0407 (14)	0.0353 (11)	0.0116 (11)	0.0115 (10)	0.0144 (10)
C5	0.0492 (15)	0.0439 (15)	0.0394 (12)	0.0130 (12)	0.0139 (11)	0.0143 (11)
C6	0.087 (2)	0.0552 (18)	0.0517 (15)	0.0236 (16)	0.0370 (15)	0.0135 (13)
C7	0.0377 (12)	0.0329 (13)	0.0336 (11)	0.0083 (10)	0.0088 (9)	0.0128 (9)
C8	0.0445 (13)	0.0371 (13)	0.0334 (11)	0.0116 (11)	0.0092 (10)	0.0095 (10)
C9	0.0524 (15)	0.0373 (14)	0.0413 (12)	0.0160 (11)	0.0189 (11)	0.0208 (11)
C10	0.0493 (14)	0.0361 (14)	0.0413 (12)	0.0132 (11)	0.0141 (11)	0.0191 (11)
C11	0.0491 (14)	0.0311 (13)	0.0392 (12)	0.0116 (11)	0.0180 (10)	0.0187 (10)
C12	0.0499 (15)	0.0432 (14)	0.0465 (13)	0.0154 (12)	0.0194 (11)	0.0233 (11)
C13	0.0530 (16)	0.0496 (16)	0.0607 (16)	0.0240 (13)	0.0294 (13)	0.0286 (13)
C14	0.0699 (18)	0.0384 (14)	0.0444 (13)	0.0172 (13)	0.0284 (12)	0.0167 (11)
C15	0.0608 (17)	0.0560 (17)	0.0397 (13)	0.0137 (14)	0.0151 (12)	0.0201 (12)
C16	0.0469 (14)	0.0488 (15)	0.0457 (13)	0.0179 (12)	0.0162 (11)	0.0225 (12)
C17	0.0732 (18)	0.0363 (14)	0.0472 (13)	0.0219 (13)	0.0229 (12)	0.0224 (11)
C18	0.066 (2)	0.0461 (17)	0.107 (2)	0.0083 (14)	0.0117 (17)	0.0453 (18)
C19	0.094 (3)	0.0490 (19)	0.118 (3)	0.0104 (17)	0.013 (2)	0.049 (2)
C22	0.064 (2)	0.067 (2)	0.094 (2)	0.0068 (16)	0.0143 (17)	0.0515 (18)
C21	0.083 (2)	0.095 (3)	0.114 (3)	0.033 (2)	0.017 (2)	0.072 (2)
F1	0.1084 (14)	0.0745 (12)	0.0571 (9)	0.0383 (10)	0.0431 (9)	0.0164 (8)
N1	0.0501 (12)	0.0334 (11)	0.0378 (9)	0.0148 (9)	0.0169 (8)	0.0176 (8)
N2	0.0613 (13)	0.0339 (11)	0.0444 (11)	0.0145 (10)	0.0197 (10)	0.0164 (9)
N3	0.0759 (16)	0.0355 (13)	0.0520 (12)	0.0212 (11)	0.0302 (11)	0.0228 (10)
O1	0.0728 (12)	0.0399 (10)	0.0524 (10)	0.0168 (9)	0.0321 (9)	0.0228 (8)
O2	0.0806 (14)	0.0645 (13)	0.0517 (10)	0.0286 (10)	0.0368 (10)	0.0311 (9)
O3	0.0627 (11)	0.0374 (10)	0.0440 (9)	0.0158 (8)	0.0218 (8)	0.0128 (8)
O4	0.1135 (16)	0.0423 (11)	0.0695 (12)	0.0402 (11)	0.0578 (11)	0.0346 (9)
C20	0.104 (3)	0.070 (2)	0.086 (2)	0.032 (2)	0.0246 (19)	0.0550 (19)

C1—C2	1.463 (4)	C12—C13	1.375 (3)
C1—H1A	0.9600	C12—H12	0.9300
C1—H1B	0.9600	C13—C14	1.365 (4)
C1—H1C	0.9600	C13—H13	0.9300
C2—O1	1.449 (3)	C14—F1	1.363 (3)
C2—H2A	0.9700	C14—C15	1.365 (4)
C2—H2B	0.9700	C15—C16	1.377 (3)
C3—O2	1.208 (3)	C15—H15	0.9300
C3—O1	1.318 (3)	C16—H16	0.9300
C3—C4	1.472 (3)	C17—N3	1.464 (3)
C4—C5	1.357 (3)	C17—C22	1.505 (4)
C4—C7	1.461 (3)	C17—C18	1.509 (4)
C5—O3	1.384 (3)	C17—H17	0.9800
C5—C6	1.478 (3)	C18—C19	1.531 (4)
C6—H6A	0.9600	C18—H18A	0.9700
C6—H6B	0.9600	C18—H18B	0.9700
C6—H6C	0.9600	C19—C20	1.504 (4)
C7—C8	1.361 (3)	C19—H19A	0.9700
C7—C9	1.432 (3)	C19—H19B	0.9700
C8—N2	1.343 (3)	C22—C21	1.522 (4)
C8—O3	1.362 (3)	C22—H22A	0.9700
C9—O4	1.207 (3)	C22—H22B	0.9700
C9—N1	1.446 (3)	C21—C20	1.498 (5)
C10—N2	1.313 (3)	C21—H21A	0.9700
C10—N3	1.352 (3)	C21—H21B	0.9700
C10—N1	1.377 (3)	N3—H3	0.86 (3)
C11—C12	1.378 (3)	C20—H20A	0.9700
C11—C16	1.383 (3)	C20—H20B	0.9700
C11—N1	1.442 (3)
C2—C1—H1A	109.5	C14—C15—C16	117.9 (2)
C2—C1—H1B	109.5	C14—C15—H15	121.1
H1A—C1—H1B	109.5	C16—C15—H15	121.1
C2—C1—H1C	109.5	C15—C16—C11	120.4 (2)
H1A—C1—H1C	109.5	C15—C16—H16	119.8
H1B—C1—H1C	109.5	C11—C16—H16	119.8
O1—C2—C1	107.8 (2)	N3—C17—C22	110.7 (2)
O1—C2—H2A	110.1	N3—C17—C18	110.7 (2)
C1—C2—H2A	110.1	C22—C17—C18	111.0 (2)
O1—C2—H2B	110.1	N3—C17—H17	108.1
C1—C2—H2B	110.1	C22—C17—H17	108.1
H2A—C2—H2B	108.5	C18—C17—H17	108.1
O2—C3—O1	123.8 (2)	C17—C18—C19	110.6 (3)
O2—C3—C4	124.9 (2)	C17—C18—H18A	109.5
O1—C3—C4	111.31 (19)	C19—C18—H18A	109.5
C5—C4—C7	106.1 (2)	C17—C18—H18B	109.5
C5—C4—C3	123.0 (2)	C19—C18—H18B	109.5
C7—C4—C3	130.9 (2)	H18A—C18—H18B	108.1
C4—C5—O3	110.5 (2)	C20—C19—C18	111.8 (3)
C4—C5—C6	134.8 (2)	C20—C19—H19A	109.2
O3—C5—C6	114.8 (2)	C18—C19—H19A	109.2
C5—C6—H6A	109.5	C20—C19—H19B	109.2
C5—C6—H6B	109.5	C18—C19—H19B	109.2
H6A—C6—H6B	109.5	H19A—C19—H19B	107.9
C5—C6—H6C	109.5	C17—C22—C21	111.6 (3)
H6A—C6—H6C	109.5	C17—C22—H22A	109.3
H6B—C6—H6C	109.5	C21—C22—H22A	109.3
C8—C7—C9	117.43 (19)	C17—C22—H22B	109.3
C8—C7—C4	105.55 (19)	C21—C22—H22B	109.3
C9—C7—C4	137.0 (2)	H22A—C22—H22B	108.0
N2—C8—C7	130.9 (2)	C20—C21—C22	111.9 (3)
N2—C8—O3	117.8 (2)	C20—C21—H21A	109.2
C7—C8—O3	111.33 (19)	C22—C21—H21A	109.2
O4—C9—C7	130.5 (2)	C20—C21—H21B	109.2
O4—C9—N1	118.1 (2)	C22—C21—H21B	109.2
C7—C9—N1	111.35 (19)	H21A—C21—H21B	107.9
N2—C10—N3	119.0 (2)	C10—N1—C11	119.56 (17)
N2—C10—N1	123.2 (2)	C10—N1—C9	124.19 (19)
N3—C10—N1	117.7 (2)	C11—N1—C9	116.10 (17)
C12—C11—C16	120.3 (2)	C10—N2—C8	112.82 (19)
C12—C11—N1	120.03 (19)	C10—N3—C17	122.8 (2)
C16—C11—N1	119.7 (2)	C10—N3—H3	114.2 (19)
C13—C12—C11	119.5 (2)	C17—N3—H3	118.7 (18)
C13—C12—H12	120.2	C3—O1—C2	118.03 (18)
C11—C12—H12	120.2	C8—O3—C5	106.58 (18)
C14—C13—C12	118.9 (2)	C21—C20—C19	111.4 (2)
C14—C13—H13	120.5	C21—C20—H20A	109.3
C12—C13—H13	120.5	C19—C20—H20A	109.3
F1—C14—C13	118.4 (2)	C21—C20—H20B	109.3
F1—C14—C15	118.5 (2)	C19—C20—H20B	109.3
C13—C14—C15	123.0 (2)	H20A—C20—H20B	108.0
O2—C3—C4—C5	1.6 (4)	N3—C17—C22—C21	179.1 (2)
O1—C3—C4—C5	−178.7 (2)	C18—C17—C22—C21	55.7 (4)
O2—C3—C4—C7	−179.5 (2)	C17—C22—C21—C20	−54.7 (4)
O1—C3—C4—C7	0.2 (3)	N2—C10—N1—C11	−172.6 (2)
C7—C4—C5—O3	−0.8 (3)	N3—C10—N1—C11	8.9 (3)
C3—C4—C5—O3	178.38 (19)	N2—C10—N1—C9	2.7 (4)
C7—C4—C5—C6	179.5 (3)	N3—C10—N1—C9	−175.9 (2)
C3—C4—C5—C6	−1.3 (4)	C12—C11—N1—C10	−107.4 (2)
C5—C4—C7—C8	0.7 (2)	C16—C11—N1—C10	72.2 (3)
C3—C4—C7—C8	−178.3 (2)	C12—C11—N1—C9	77.0 (3)
C5—C4—C7—C9	−179.3 (3)	C16—C11—N1—C9	−103.4 (2)
C3—C4—C7—C9	1.6 (4)	O4—C9—N1—C10	177.3 (2)
C9—C7—C8—N2	−0.6 (4)	C7—C9—N1—C10	−3.6 (3)
C4—C7—C8—N2	179.4 (2)	O4—C9—N1—C11	−7.3 (3)
C9—C7—C8—O3	179.58 (18)	C7—C9—N1—C11	171.78 (18)
C4—C7—C8—O3	−0.4 (2)	N3—C10—N2—C8	178.2 (2)
C8—C7—C9—O4	−178.6 (3)	N1—C10—N2—C8	−0.3 (3)
C4—C7—C9—O4	1.4 (5)	C7—C8—N2—C10	−0.7 (4)
C8—C7—C9—N1	2.5 (3)	O3—C8—N2—C10	179.16 (19)
C4—C7—C9—N1	−177.5 (2)	N2—C10—N3—C17	19.9 (4)
C16—C11—C12—C13	−0.2 (3)	N1—C10—N3—C17	−161.5 (2)
N1—C11—C12—C13	179.3 (2)	C22—C17—N3—C10	90.1 (3)
C11—C12—C13—C14	−0.1 (3)	C18—C17—N3—C10	−146.4 (3)
C12—C13—C14—F1	−179.7 (2)	O2—C3—O1—C2	4.3 (3)
C12—C13—C14—C15	0.2 (4)	C4—C3—O1—C2	−175.4 (2)
F1—C14—C15—C16	180.0 (2)	C1—C2—O1—C3	172.4 (2)
C13—C14—C15—C16	0.1 (4)	N2—C8—O3—C5	−179.9 (2)
C14—C15—C16—C11	−0.4 (4)	C7—C8—O3—C5	0.0 (2)
C12—C11—C16—C15	0.5 (3)	C4—C5—O3—C8	0.5 (3)
N1—C11—C16—C15	−179.1 (2)	C6—C5—O3—C8	−179.7 (2)
N3—C17—C18—C19	−179.1 (2)	C22—C21—C20—C19	53.8 (4)
C22—C17—C18—C19	−55.8 (4)	C18—C19—C20—C21	−54.4 (4)
C17—C18—C19—C20	55.4 (4)

D—H···A	D—H	H···A	D···A	D—H···A
C17—H17···N2	0.98	2.41	2.813 (3)	104
C6—H6A···O2	0.96	2.45	3.039 (3)	120
C20—H20B···Cg3i	0.97	2.97	3.820 (4)	147
C14—F···Cg3ii	1.363 (3)	3.358 (2)	3.732 (3)	95
C3—O2···Cg2iii	1.208 (3)	3.309 (2)	3.409 (3)	84

Table 1

Hydrogen-bond and C—F⋯π and C—O⋯π interactions (Å, °)

Cg2 and Cg3 are the centroids of the N1/C9/C7/C8/N2/C10 and C11–C16 rings, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C17—H17⋯N2	0.98	2.41	2.813 (3)	104
C6—H6A⋯O2	0.96	2.45	3.039 (3)	120
C20—H20B⋯Cg3i	0.97	2.97	3.820 (4)	147
C14—F1⋯Cg3ii	1.36 (1)	3.36 (1)	3.732 (3)	95
C3—O2⋯Cg2iii	1.21 (1)	3.31 (1)	3.409 (3)	84