Pelanserin: 3-[3-(4-phenyl-piperazin-1-yl)prop-yl]quinazoline-2,4(1H,3H)-dione.

The title compound, C21H24N4O2, is a potent serotonin 5-HT2 and α1-adrenoceptor antagonist. The n-propyl chain links the quinazolinedione heterocycle and the phenyl-piperazine group in which the benzene ring is equatorially located and the piperazine ring has the expected chair conformation. The dihedral angle between the planes of the benzene ring and the quinazolinedione ring system is 74.1 (1)°. In the crystal, mol-ecules form centrosymmetric dimers through R 2 (2)(8) hydrogen-bonded rings involving the amine and one carbonyl group of the quinazolinedione moiety. These dimers are extended into chains extending along the a-axis direction through expanded centrosymmetric cyclic C-H⋯O associations involving the second carbonyl group, giving R 2 (2)(20) and R 1 (2)(7) motifs.

Related literature

For the synthesis of pelanserin, see: Cortez et al. (1991 ▶); Garcia et al. (2000 ▶); Li et al. (2011 ▶). For the pharmacology of pelanserin, see: Flores-Murrieta et al. (1990 ▶, 1992 ▶); Villalobos-Molina et al. (1995 ▶). For the structure of quinazoline-2,4(1H,3H)-dione, see: Liu (2008 ▶).

Experimental

Crystal data

C21H24N4O2

M = 364.44

Monoclinic,

a = 15.7531 (17) Å

b = 5.4345 (10) Å

c = 22.756 (3) Å

β = 104.506 (9)°

V = 1886.0 (5) Å3

Z = 4

Mo Kα radiation

μ = 0.09 mm−1

T = 296 K

0.60 × 0.30 × 0.10 mm

Data collection

Bruker P4 diffractometer

3452 measured reflections

3323 independent reflections

1301 reflections with I > 2σ(I)

R int = 0.077

3 standard reflections every 97 reflections intensity decay: 1%

Refinement

R[F 2 > 2σ(F 2)] = 0.072

wR(F 2) = 0.148

S = 0.99

3323 reflections

247 parameters

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.18 e Å−3

Δρmin = −0.19 e Å−3

Data collection: XSCANS (Siemens, 1996 ▶); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXS2013 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008 ▶); molecular graphics: Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: SHELXL2013.

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S160053681401602X/zs2304sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S160053681401602X/zs2304Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S160053681401602X/zs2304Isup3.cml

CCDC reference: 1013055

Additional supporting information: crystallographic information; 3D view; checkCIF report

C21H24N4O2	Dx = 1.283 Mg m−3
Mr = 364.44	Melting point = 463–465 K
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 15.7531 (17) Å	Cell parameters from 33 reflections
b = 5.4345 (10) Å	θ = 4.7–10.7°
c = 22.756 (3) Å	µ = 0.09 mm−1
β = 104.506 (9)°	T = 296 K
V = 1886.0 (5) Å3	Plate, yellow
Z = 4	0.60 × 0.30 × 0.10 mm
F(000) = 776

Bruker P4 diffractometer	Rint = 0.077
Radiation source: fine-focus sealed tube	θmax = 25.0°, θmin = 2.5°
Graphite monochromator	h = 0→18
2θ/ω scans	k = 0→6
3452 measured reflections	l = −27→26
3323 independent reflections	3 standard reflections every 97 reflections
1301 reflections with I > 2σ(I)	intensity decay: 1%

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)] = 0.072	Hydrogen site location: mixed
wR(F2) = 0.148	H atoms treated by a mixture of independent and constrained refinement
S = 0.99	w = 1/[σ2(Fo2) + (0.0399P)2] where P = (Fo2 + 2Fc2)/3
3323 reflections	(Δ/σ)max < 0.001
247 parameters	Δρmax = 0.18 e Å−3
0 restraints	Δρmin = −0.19 e Å−3
0 constraints

	x	y	z	Uiso*/Ueq
N1	0.8261 (2)	0.4446 (7)	0.56297 (15)	0.0441 (10)
C2	0.8955 (3)	0.4694 (10)	0.5359 (2)	0.0476 (13)
O2	0.90428 (19)	0.3299 (6)	0.49494 (13)	0.0615 (10)
N3	0.9524 (2)	0.6547 (8)	0.55692 (17)	0.0510 (11)
H3	1.004 (3)	0.669 (8)	0.5430 (17)	0.061*
C4	0.9477 (3)	0.8081 (9)	0.60436 (19)	0.0437 (12)
C5	1.0100 (3)	0.9929 (9)	0.6239 (2)	0.0530 (14)
H5A	1.0556	1.0136	0.6051	0.064*
C6	1.0035 (3)	1.1443 (10)	0.6712 (2)	0.0602 (14)
H6A	1.0447	1.2681	0.6842	0.072*
C7	0.9361 (3)	1.1131 (10)	0.6995 (2)	0.0592 (14)
H7A	0.9326	1.2143	0.7318	0.071*
C8	0.8741 (3)	0.9326 (9)	0.6800 (2)	0.0536 (14)
H8A	0.8282	0.9145	0.6986	0.064*
C9	0.8798 (3)	0.7762 (9)	0.63228 (18)	0.0416 (12)
C10	0.8130 (3)	0.5898 (9)	0.61014 (19)	0.0457 (12)
O10	0.7479 (2)	0.5615 (6)	0.62947 (13)	0.0649 (10)
C11	0.7659 (3)	0.2377 (9)	0.54229 (18)	0.0488 (13)
H11A	0.7447	0.1788	0.5763	0.059*
H11B	0.7982	0.1045	0.5296	0.059*
C12	0.6878 (3)	0.3001 (9)	0.49053 (18)	0.0506 (13)
H12A	0.7075	0.3740	0.4575	0.061*
H12B	0.6502	0.4169	0.5041	0.061*
C13	0.6375 (3)	0.0642 (9)	0.46908 (18)	0.0502 (13)
H13A	0.6737	−0.0416	0.4510	0.060*
H13B	0.6271	−0.0211	0.5041	0.060*
N14	0.5535 (2)	0.1028 (7)	0.42500 (15)	0.0435 (10)
C15	0.5664 (3)	0.1797 (9)	0.36668 (18)	0.0551 (14)
H15A	0.6014	0.0573	0.3524	0.066*
H15B	0.5985	0.3337	0.3717	0.066*
C16	0.4801 (3)	0.2128 (9)	0.31949 (19)	0.0605 (14)
H16A	0.4476	0.3471	0.3317	0.073*
H16B	0.4917	0.2565	0.2809	0.073*
N17	0.4269 (2)	−0.0093 (7)	0.31190 (15)	0.0432 (10)
C18	0.4153 (3)	−0.0908 (9)	0.37070 (18)	0.0528 (13)
H18A	0.3833	−0.2451	0.3657	0.063*
H18B	0.3811	0.0302	0.3862	0.063*
C19	0.5027 (3)	−0.1247 (9)	0.41534 (19)	0.0555 (14)
H19A	0.4935	−0.1805	0.4538	0.067*
H19B	0.5356	−0.2507	0.4004	0.067*
C20	0.3524 (3)	−0.0201 (9)	0.26258 (19)	0.0446 (12)
C21	0.3356 (3)	0.1559 (10)	0.2177 (2)	0.0651 (16)
H21A	0.3723	0.2919	0.2209	0.078*
C22	0.2645 (3)	0.1331 (11)	0.1677 (2)	0.0708 (17)
H22A	0.2545	0.2541	0.1378	0.085*
C23	0.2089 (3)	−0.0630 (11)	0.1614 (2)	0.0643 (15)
H23A	0.1614	−0.0777	0.1278	0.077*
C24	0.2254 (3)	−0.2380 (11)	0.2063 (2)	0.0656 (15)
H24A	0.1878	−0.3722	0.2031	0.079*
C25	0.2961 (3)	−0.2202 (10)	0.2562 (2)	0.0559 (14)
H25A	0.3061	−0.3428	0.2857	0.067*

	U11	U22	U33	U12	U13	U23
N1	0.033 (2)	0.057 (3)	0.043 (2)	−0.005 (2)	0.0113 (18)	0.003 (2)
C2	0.032 (3)	0.069 (4)	0.038 (3)	0.001 (3)	0.000 (2)	0.000 (3)
O2	0.059 (2)	0.079 (3)	0.0492 (19)	−0.012 (2)	0.0193 (17)	−0.019 (2)
N3	0.037 (2)	0.065 (3)	0.052 (2)	−0.010 (2)	0.013 (2)	−0.008 (2)
C4	0.039 (3)	0.049 (3)	0.040 (3)	0.002 (3)	0.005 (2)	0.001 (3)
C5	0.040 (3)	0.063 (4)	0.053 (3)	0.001 (3)	0.005 (2)	0.012 (3)
C6	0.057 (3)	0.056 (4)	0.061 (3)	−0.002 (3)	0.002 (3)	−0.002 (3)
C7	0.065 (3)	0.056 (4)	0.054 (3)	0.006 (3)	0.010 (3)	−0.005 (3)
C8	0.047 (3)	0.063 (4)	0.050 (3)	0.014 (3)	0.011 (2)	0.007 (3)
C9	0.039 (3)	0.048 (3)	0.034 (2)	0.012 (3)	0.003 (2)	0.007 (2)
C10	0.042 (3)	0.051 (3)	0.042 (3)	0.006 (3)	0.007 (2)	0.004 (3)
O10	0.054 (2)	0.079 (3)	0.073 (2)	−0.009 (2)	0.0345 (18)	−0.008 (2)
C11	0.036 (3)	0.061 (3)	0.049 (3)	−0.001 (3)	0.010 (2)	0.004 (3)
C12	0.044 (3)	0.052 (3)	0.048 (3)	−0.005 (3)	−0.002 (2)	0.002 (3)
C13	0.048 (3)	0.051 (3)	0.048 (3)	−0.001 (3)	0.005 (2)	−0.003 (3)
N14	0.044 (2)	0.046 (3)	0.039 (2)	−0.006 (2)	0.0074 (18)	−0.005 (2)
C15	0.051 (3)	0.064 (4)	0.048 (3)	−0.015 (3)	0.008 (2)	0.000 (3)
C16	0.059 (3)	0.064 (4)	0.055 (3)	−0.016 (3)	0.007 (3)	0.006 (3)
N17	0.045 (2)	0.048 (3)	0.038 (2)	−0.010 (2)	0.0131 (18)	0.000 (2)
C18	0.047 (3)	0.062 (4)	0.048 (3)	−0.018 (3)	0.008 (2)	−0.001 (3)
C19	0.060 (3)	0.060 (4)	0.045 (3)	−0.011 (3)	0.012 (2)	0.000 (3)
C20	0.044 (3)	0.050 (3)	0.039 (3)	0.002 (3)	0.008 (2)	−0.010 (3)
C21	0.077 (4)	0.067 (4)	0.044 (3)	−0.011 (3)	0.000 (3)	−0.002 (3)
C22	0.076 (4)	0.076 (4)	0.051 (3)	0.001 (4)	0.000 (3)	0.008 (3)
C23	0.049 (3)	0.087 (4)	0.054 (3)	0.000 (4)	0.007 (3)	−0.011 (3)
C24	0.053 (3)	0.079 (4)	0.064 (3)	−0.022 (3)	0.015 (3)	−0.016 (4)
C25	0.049 (3)	0.058 (4)	0.056 (3)	−0.005 (3)	0.004 (3)	−0.006 (3)

N1—C2	1.389 (5)	C13—H13B	0.9700
N1—C10	1.389 (5)	N14—C15	1.453 (5)
N1—C11	1.470 (5)	N14—C19	1.459 (5)
C2—O2	1.235 (5)	C15—C16	1.518 (5)
C2—N3	1.353 (5)	C15—H15A	0.9700
N3—C4	1.381 (5)	C15—H15B	0.9700
N3—H3	0.95 (4)	C16—N17	1.454 (5)
C4—C9	1.385 (5)	C16—H16A	0.9700
C4—C5	1.397 (6)	C16—H16B	0.9700
C5—C6	1.379 (6)	N17—C20	1.407 (5)
C5—H5A	0.9300	N17—C18	1.464 (5)
C6—C7	1.384 (6)	C18—C19	1.504 (5)
C6—H6A	0.9300	C18—H18A	0.9700
C7—C8	1.377 (6)	C18—H18B	0.9700
C7—H7A	0.9300	C19—H19A	0.9700
C8—C9	1.400 (6)	C19—H19B	0.9700
C8—H8A	0.9300	C20—C21	1.375 (6)
C9—C10	1.456 (6)	C20—C25	1.388 (6)
C10—O10	1.223 (5)	C21—C22	1.388 (6)
C11—C12	1.513 (5)	C21—H21A	0.9300
C11—H11A	0.9700	C22—C23	1.364 (6)
C11—H11B	0.9700	C22—H22A	0.9300
C12—C13	1.522 (6)	C23—C24	1.373 (6)
C12—H12A	0.9700	C23—H23A	0.9300
C12—H12B	0.9700	C24—C25	1.381 (5)
C13—N14	1.462 (5)	C24—H24A	0.9300
C13—H13A	0.9700	C25—H25A	0.9300
C2—N1—C10	125.0 (4)	C15—N14—C19	107.6 (3)
C2—N1—C11	116.7 (4)	C15—N14—C13	111.0 (3)
C10—N1—C11	118.2 (4)	C19—N14—C13	110.5 (4)
O2—C2—N3	122.3 (4)	N14—C15—C16	112.0 (4)
O2—C2—N1	121.6 (5)	N14—C15—H15A	109.2
N3—C2—N1	116.1 (5)	C16—C15—H15A	109.2
C2—N3—C4	124.4 (4)	N14—C15—H15B	109.2
C2—N3—H3	119 (3)	C16—C15—H15B	109.2
C4—N3—H3	115 (3)	H15A—C15—H15B	107.9
N3—C4—C9	118.8 (5)	N17—C16—C15	111.9 (4)
N3—C4—C5	120.7 (5)	N17—C16—H16A	109.2
C9—C4—C5	120.4 (5)	C15—C16—H16A	109.2
C6—C5—C4	119.6 (5)	N17—C16—H16B	109.2
C6—C5—H5A	120.2	C15—C16—H16B	109.2
C4—C5—H5A	120.2	H16A—C16—H16B	107.9
C5—C6—C7	120.4 (5)	C20—N17—C16	118.0 (4)
C5—C6—H6A	119.8	C20—N17—C18	116.5 (3)
C7—C6—H6A	119.8	C16—N17—C18	110.1 (3)
C8—C7—C6	120.1 (5)	N17—C18—C19	110.6 (3)
C8—C7—H7A	119.9	N17—C18—H18A	109.5
C6—C7—H7A	119.9	C19—C18—H18A	109.5
C7—C8—C9	120.3 (5)	N17—C18—H18B	109.5
C7—C8—H8A	119.8	C19—C18—H18B	109.5
C9—C8—H8A	119.8	H18A—C18—H18B	108.1
C4—C9—C8	119.1 (5)	N14—C19—C18	111.9 (4)
C4—C9—C10	120.1 (4)	N14—C19—H19A	109.2
C8—C9—C10	120.6 (5)	C18—C19—H19A	109.2
O10—C10—N1	120.5 (5)	N14—C19—H19B	109.2
O10—C10—C9	124.1 (5)	C18—C19—H19B	109.2
N1—C10—C9	115.4 (4)	H19A—C19—H19B	107.9
N1—C11—C12	114.3 (4)	C21—C20—C25	117.9 (4)
N1—C11—H11A	108.7	C21—C20—N17	122.0 (5)
C12—C11—H11A	108.7	C25—C20—N17	119.9 (4)
N1—C11—H11B	108.7	C20—C21—C22	120.8 (5)
C12—C11—H11B	108.7	C20—C21—H21A	119.6
H11A—C11—H11B	107.6	C22—C21—H21A	119.6
C11—C12—C13	108.5 (4)	C23—C22—C21	121.4 (5)
C11—C12—H12A	110.0	C23—C22—H22A	119.3
C13—C12—H12A	110.0	C21—C22—H22A	119.3
C11—C12—H12B	110.0	C22—C23—C24	117.8 (5)
C13—C12—H12B	110.0	C22—C23—H23A	121.1
H12A—C12—H12B	108.4	C24—C23—H23A	121.1
N14—C13—C12	114.1 (4)	C23—C24—C25	121.8 (5)
N14—C13—H13A	108.7	C23—C24—H24A	119.1
C12—C13—H13A	108.7	C25—C24—H24A	119.1
N14—C13—H13B	108.7	C24—C25—C20	120.2 (5)
C12—C13—H13B	108.7	C24—C25—H25A	119.9
H13A—C13—H13B	107.6	C20—C25—H25A	119.9
C10—N1—C2—O2	178.3 (4)	C10—N1—C11—C12	92.2 (4)
C11—N1—C2—O2	2.5 (6)	N1—C11—C12—C13	173.4 (4)
C10—N1—C2—N3	−1.7 (6)	C11—C12—C13—N14	171.7 (3)
C11—N1—C2—N3	−177.5 (4)	C12—C13—N14—C15	71.1 (5)
O2—C2—N3—C4	−176.9 (4)	C12—C13—N14—C19	−169.6 (4)
N1—C2—N3—C4	3.1 (6)	C19—N14—C15—C16	57.1 (5)
C2—N3—C4—C9	−1.2 (6)	C13—N14—C15—C16	178.1 (4)
C2—N3—C4—C5	179.0 (4)	N14—C15—C16—N17	−56.3 (5)
N3—C4—C5—C6	179.7 (4)	C15—C16—N17—C20	−169.2 (4)
C9—C4—C5—C6	−0.1 (6)	C15—C16—N17—C18	53.8 (5)
C4—C5—C6—C7	0.4 (7)	C20—N17—C18—C19	167.0 (4)
C5—C6—C7—C8	−1.0 (7)	C16—N17—C18—C19	−55.2 (5)
C6—C7—C8—C9	1.3 (7)	C15—N14—C19—C18	−59.3 (5)
N3—C4—C9—C8	−179.4 (4)	C13—N14—C19—C18	179.4 (3)
C5—C4—C9—C8	0.5 (6)	N17—C18—C19—N14	59.6 (5)
N3—C4—C9—C10	−2.3 (6)	C16—N17—C20—C21	8.9 (6)
C5—C4—C9—C10	177.5 (4)	C18—N17—C20—C21	143.2 (4)
C7—C8—C9—C4	−1.1 (6)	C16—N17—C20—C25	−175.1 (4)
C7—C8—C9—C10	−178.1 (4)	C18—N17—C20—C25	−40.7 (6)
C2—N1—C10—O10	176.8 (4)	C25—C20—C21—C22	−0.1 (7)
C11—N1—C10—O10	−7.4 (6)	N17—C20—C21—C22	176.1 (4)
C2—N1—C10—C9	−1.5 (6)	C20—C21—C22—C23	0.3 (8)
C11—N1—C10—C9	174.3 (3)	C21—C22—C23—C24	0.1 (8)
C4—C9—C10—O10	−174.7 (4)	C22—C23—C24—C25	−0.7 (8)
C8—C9—C10—O10	2.3 (7)	C23—C24—C25—C20	0.9 (7)
C4—C9—C10—N1	3.5 (6)	C21—C20—C25—C24	−0.5 (7)
C8—C9—C10—N1	−179.5 (4)	N17—C20—C25—C24	−176.7 (4)
C2—N1—C11—C12	−91.7 (4)

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3···O2i	0.95 (4)	1.85 (4)	2.799 (5)	171 (4)
C18—H18A···O10ii	0.97	2.71	3.625 (6)	157
C25—H25A···O10ii	0.93	2.59	3.404 (6)	147

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H3⋯O2i	0.95 (4)	1.85 (4)	2.799 (5)	171 (4)
C18—H18A⋯O10ii	0.97	2.71	3.625 (6)	157
C25—H25A⋯O10ii	0.93	2.59	3.404 (6)	147

Symmetry codes: (i) ; (ii) .