tert-Butyl 4-{[2-amino-4-(2-hy-droxy-phen-yl)pyrimidin-5-yl]meth-yl}piperazine-1-carboxyl-ate.

In the title compound, C20H27N5O3, the central piperazine ring adopts a chair conformation, with the N-bound carboxyl-ate and methyl-ene substituents occupying bis-ectional and equatorial orientations, respectively. A twist is evident between the aromatic rings [dihedral angle = 25.61 (9)°] but an intra-molecular O-H⋯N hydrogen bond persists between these. Supra-molecular tapes along [1-10] are formed in the crystal packing through N(amino)-H⋯O(hydrox-yl) and N(amino)-H⋯N(pyrimidin-yl) hydrogen bonds, and these are linked into layers in the ab plane by π-π inter-actions [inter-centroid distance between pyrimidinyl rings = 3.5919 (9) Å].

Related literature

For the biological activity of pyrimidine-containing heterocyclic compounds, see: Topalis et al. (2011 ▶); Sbardella et al. (2011 ▶); Zhang et al. (2011 ▶). For the synthesis, see: Patel et al. (2011 ▶).

Experimental

Crystal data

C20H27N5O3

M = 385.47

Monoclinic,

a = 6.1925 (2) Å

b = 8.2636 (2) Å

c = 40.7287 (11) Å

β = 93.513 (2)°

V = 2080.27 (10) Å3

Z = 4

Mo Kα radiation

μ = 0.09 mm−1

T = 293 K

0.47 × 0.35 × 0.31 mm

Data collection

Bruker APEXII CCD diffractometer

Absorption correction: multi-scan (SADABS; Bruker, 2004 ▶) T min = 0.980, T max = 0.997

20251 measured reflections

4985 independent reflections

3339 reflections with I > 2σ(I)

R int = 0.026

Refinement

R[F 2 > 2σ(F 2)] = 0.050

wR(F 2) = 0.141

S = 1.04

4984 reflections

265 parameters

3 restraints

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.19 e Å−3

Δρmin = −0.17 e Å−3

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: APEX2 and SAINT (Bruker, 2004 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▶) and DIAMOND (Brandenburg, 2006 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Crystal structure: contains datablock(s) general, I. DOI: 10.1107/S1600536813025774/hg5347sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813025774/hg5347Isup2.hkl

Click here for additional data file.

Supplementary material file. DOI: 10.1107/S1600536813025774/hg5347Isup3.cml

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

C20H27N5O3	F(000) = 824
Mr = 385.47	Dx = 1.231 Mg m−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 5662 reflections
a = 6.1925 (2) Å	θ = 2.5–24.9°
b = 8.2636 (2) Å	µ = 0.09 mm−1
c = 40.7287 (11) Å	T = 293 K
β = 93.513 (2)°	Block, yellow
V = 2080.27 (10) Å3	0.47 × 0.35 × 0.31 mm
Z = 4

Bruker APEXII CCD diffractometer	4985 independent reflections
Radiation source: fine-focus sealed tube	3339 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.026
Detector resolution: 10.0 pixels mm-1	θmax = 28.1°, θmin = 1.0°
ω and φ scan	h = −8→8
Absorption correction: multi-scan (SADABS; Bruker, 2004)	k = −10→10
Tmin = 0.980, Tmax = 0.997	l = −53→53
20251 measured reflections

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)] = 0.050	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.141	H atoms treated by a mixture of independent and constrained refinement
S = 1.04	w = 1/[σ2(Fo2) + (0.0598P)2 + 0.4709P] where P = (Fo2 + 2Fc2)/3
4984 reflections	(Δ/σ)max < 0.001
265 parameters	Δρmax = 0.19 e Å−3
3 restraints	Δρmin = −0.17 e Å−3

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(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
O1	0.91283 (18)	0.00416 (15)	0.20530 (3)	0.0595 (3)
O2	1.2654 (2)	0.03360 (18)	0.19456 (4)	0.0730 (4)
O3	0.7761 (2)	0.93303 (17)	0.02308 (4)	0.0754 (4)
H1O	0.890 (3)	0.881 (3)	0.0213 (7)	0.113*
N1	1.0148 (2)	0.2184 (2)	0.17776 (4)	0.0570 (4)
N2	0.89391 (19)	0.36533 (16)	0.11658 (3)	0.0439 (3)
N3	1.2749 (2)	0.47841 (18)	0.02609 (3)	0.0547 (4)
N4	1.0670 (2)	0.71577 (17)	0.03355 (3)	0.0485 (3)
N5	1.3458 (3)	0.7126 (2)	−0.00122 (4)	0.0586 (4)
H1N	1.453 (2)	0.660 (2)	−0.0085 (5)	0.070*
H2N	1.313 (3)	0.8128 (13)	−0.0043 (5)	0.070*
C1	0.9389 (3)	−0.1517 (2)	0.22215 (5)	0.0643 (5)
C2	0.7106 (4)	−0.1849 (3)	0.23163 (7)	0.0982 (8)
H2A	0.6168	−0.1958	0.2121	0.147*
H2B	0.6619	−0.0968	0.2446	0.147*
H2C	0.7084	−0.2833	0.2442	0.147*
C3	1.0205 (6)	−0.2767 (3)	0.19926 (8)	0.1142 (10)
H3A	0.9265	−0.2812	0.1796	0.171*
H3B	1.0233	−0.3805	0.2099	0.171*
H3C	1.1640	−0.2485	0.1936	0.171*
C4	1.0877 (4)	−0.1339 (3)	0.25247 (6)	0.0862 (7)
H4A	1.2309	−0.1087	0.2462	0.129*
H4B	1.0909	−0.2334	0.2647	0.129*
H4C	1.0365	−0.0483	0.2659	0.129*
C5	1.0795 (3)	0.0788 (2)	0.19248 (4)	0.0502 (4)
C6	1.1675 (3)	0.3157 (3)	0.16089 (4)	0.0583 (5)
H6A	1.3126	0.2742	0.1656	0.070*
H6B	1.1633	0.4263	0.1688	0.070*
C7	1.1151 (2)	0.3135 (2)	0.12434 (4)	0.0505 (4)
H7A	1.2135	0.3848	0.1136	0.061*
H7B	1.1346	0.2048	0.1160	0.061*
C8	0.7452 (2)	0.2609 (2)	0.13308 (4)	0.0539 (4)
H8A	0.7585	0.1509	0.1251	0.065*
H8B	0.5978	0.2965	0.1278	0.065*
C9	0.7909 (3)	0.2634 (2)	0.16981 (4)	0.0571 (5)
H9A	0.7641	0.3710	0.1782	0.069*
H9B	0.6955	0.1883	0.1801	0.069*
C10	0.8377 (3)	0.3662 (2)	0.08106 (4)	0.0501 (4)
H10A	0.6881	0.3998	0.0774	0.060*
H10B	0.8489	0.2566	0.0728	0.060*
C11	0.9763 (3)	0.4747 (2)	0.06151 (4)	0.0461 (4)
C12	1.1442 (3)	0.4048 (2)	0.04594 (4)	0.0523 (4)
H12	1.1684	0.2951	0.0497	0.063*
C13	1.2268 (3)	0.6347 (2)	0.02015 (4)	0.0482 (4)
C14	0.9433 (2)	0.6398 (2)	0.05486 (4)	0.0452 (4)
C15	0.7717 (3)	0.7411 (2)	0.06797 (4)	0.0496 (4)
C16	0.6802 (3)	0.7041 (3)	0.09754 (5)	0.0661 (5)
H16	0.7374	0.6190	0.1102	0.079*
C17	0.5086 (4)	0.7892 (3)	0.10848 (6)	0.0808 (6)
H17	0.4508	0.7621	0.1283	0.097*
C18	0.4230 (4)	0.9149 (3)	0.08982 (6)	0.0800 (6)
H18	0.3016	0.9694	0.0964	0.096*
C19	0.5151 (3)	0.9602 (2)	0.06172 (6)	0.0712 (6)
H19	0.4582	1.0475	0.0497	0.085*
C20	0.6908 (3)	0.8788 (2)	0.05086 (5)	0.0567 (4)

	U11	U22	U33	U12	U13	U23
O1	0.0471 (6)	0.0574 (7)	0.0739 (8)	0.0036 (5)	0.0027 (6)	0.0193 (6)
O2	0.0452 (7)	0.0813 (9)	0.0922 (10)	0.0159 (7)	0.0017 (6)	0.0178 (8)
O3	0.0799 (10)	0.0616 (9)	0.0863 (10)	0.0078 (7)	0.0171 (8)	0.0277 (7)
N1	0.0377 (7)	0.0774 (10)	0.0562 (8)	0.0055 (7)	0.0054 (6)	0.0268 (7)
N2	0.0354 (6)	0.0546 (8)	0.0422 (7)	0.0024 (6)	0.0075 (5)	0.0110 (6)
N3	0.0592 (8)	0.0581 (9)	0.0484 (8)	−0.0008 (7)	0.0160 (7)	0.0056 (7)
N4	0.0494 (7)	0.0532 (8)	0.0432 (7)	−0.0058 (6)	0.0048 (6)	0.0056 (6)
N5	0.0649 (10)	0.0591 (9)	0.0535 (9)	−0.0065 (8)	0.0181 (7)	0.0079 (7)
C1	0.0691 (12)	0.0473 (10)	0.0758 (13)	0.0031 (9)	−0.0005 (10)	0.0118 (9)
C2	0.0747 (15)	0.0852 (16)	0.134 (2)	−0.0138 (13)	0.0032 (14)	0.0445 (16)
C3	0.156 (3)	0.0629 (15)	0.124 (2)	0.0019 (17)	0.011 (2)	−0.0182 (15)
C4	0.0856 (15)	0.0896 (16)	0.0818 (15)	0.0095 (13)	−0.0074 (12)	0.0244 (13)
C5	0.0421 (9)	0.0593 (10)	0.0487 (9)	0.0045 (8)	0.0001 (7)	0.0036 (8)
C6	0.0403 (8)	0.0773 (12)	0.0574 (10)	−0.0038 (8)	0.0026 (7)	0.0172 (9)
C7	0.0358 (8)	0.0628 (10)	0.0540 (9)	0.0031 (7)	0.0112 (7)	0.0118 (8)
C8	0.0333 (8)	0.0714 (11)	0.0573 (10)	0.0014 (8)	0.0060 (7)	0.0216 (8)
C9	0.0411 (8)	0.0762 (12)	0.0554 (10)	0.0142 (8)	0.0142 (7)	0.0245 (9)
C10	0.0463 (9)	0.0600 (10)	0.0444 (9)	−0.0030 (8)	0.0053 (7)	0.0093 (7)
C11	0.0469 (8)	0.0537 (9)	0.0378 (8)	−0.0015 (7)	0.0033 (6)	0.0070 (7)
C12	0.0597 (10)	0.0529 (10)	0.0454 (9)	0.0014 (8)	0.0122 (7)	0.0069 (7)
C13	0.0506 (9)	0.0558 (10)	0.0385 (8)	−0.0084 (8)	0.0047 (7)	0.0028 (7)
C14	0.0428 (8)	0.0546 (9)	0.0377 (8)	−0.0033 (7)	−0.0005 (6)	0.0035 (7)
C15	0.0475 (9)	0.0512 (9)	0.0500 (9)	−0.0018 (7)	0.0027 (7)	0.0020 (7)
C16	0.0683 (12)	0.0707 (12)	0.0607 (11)	0.0132 (10)	0.0153 (9)	0.0075 (9)
C17	0.0839 (15)	0.0805 (15)	0.0813 (15)	0.0171 (12)	0.0316 (12)	0.0045 (12)
C18	0.0726 (13)	0.0613 (13)	0.1083 (18)	0.0137 (11)	0.0234 (13)	−0.0116 (12)
C19	0.0693 (12)	0.0494 (11)	0.0952 (16)	0.0089 (9)	0.0092 (11)	0.0029 (10)
C20	0.0567 (10)	0.0460 (9)	0.0672 (11)	−0.0044 (8)	0.0020 (8)	0.0042 (8)

O1—C5	1.336 (2)	C4—H4C	0.9600
O1—C1	1.464 (2)	C6—C7	1.504 (2)
O2—C5	1.2080 (19)	C6—H6A	0.9700
O3—C20	1.354 (2)	C6—H6B	0.9700
O3—H1O	0.832 (10)	C7—H7A	0.9700
N1—C5	1.350 (2)	C7—H7B	0.9700
N1—C6	1.447 (2)	C8—C9	1.505 (2)
N1—C9	1.453 (2)	C8—H8A	0.9700
N2—C7	1.4513 (19)	C8—H8B	0.9700
N2—C8	1.4564 (19)	C9—H9A	0.9700
N2—C10	1.467 (2)	C9—H9B	0.9700
N3—C12	1.326 (2)	C10—C11	1.503 (2)
N3—C13	1.345 (2)	C10—H10A	0.9700
N4—C13	1.338 (2)	C10—H10B	0.9700
N4—C14	1.3476 (19)	C11—C12	1.378 (2)
N5—C13	1.339 (2)	C11—C14	1.403 (2)
N5—H1N	0.861 (9)	C12—H12	0.9300
N5—H2N	0.859 (9)	C14—C15	1.477 (2)
C1—C4	1.502 (3)	C15—C16	1.396 (2)
C1—C3	1.500 (3)	C15—C20	1.411 (2)
C1—C2	1.513 (3)	C16—C17	1.371 (3)
C2—H2A	0.9600	C16—H16	0.9300
C2—H2B	0.9600	C17—C18	1.375 (3)
C2—H2C	0.9600	C17—H17	0.9300
C3—H3A	0.9600	C18—C19	1.362 (3)
C3—H3B	0.9600	C18—H18	0.9300
C3—H3C	0.9600	C19—C20	1.375 (3)
C4—H4A	0.9600	C19—H19	0.9300
C4—H4B	0.9600
C5—O1—C1	121.59 (13)	C6—C7—H7B	109.5
C20—O3—H1O	106 (2)	H7A—C7—H7B	108.1
C5—N1—C6	120.09 (14)	N2—C8—C9	111.36 (14)
C5—N1—C9	124.84 (14)	N2—C8—H8A	109.4
C6—N1—C9	113.22 (13)	C9—C8—H8A	109.4
C7—N2—C8	109.85 (12)	N2—C8—H8B	109.4
C7—N2—C10	112.32 (12)	C9—C8—H8B	109.4
C8—N2—C10	109.84 (12)	H8A—C8—H8B	108.0
C12—N3—C13	114.41 (15)	N1—C9—C8	109.68 (13)
C13—N4—C14	119.56 (14)	N1—C9—H9A	109.7
C13—N5—H1N	116.6 (14)	C8—C9—H9A	109.7
C13—N5—H2N	115.1 (14)	N1—C9—H9B	109.7
H1N—N5—H2N	128 (2)	C8—C9—H9B	109.7
O1—C1—C4	110.10 (16)	H9A—C9—H9B	108.2
O1—C1—C3	110.25 (18)	N2—C10—C11	114.62 (13)
C4—C1—C3	111.4 (2)	N2—C10—H10A	108.6
O1—C1—C2	101.62 (15)	C11—C10—H10A	108.6
C4—C1—C2	110.11 (19)	N2—C10—H10B	108.6
C3—C1—C2	112.9 (2)	C11—C10—H10B	108.6
C1—C2—H2A	109.5	H10A—C10—H10B	107.6
C1—C2—H2B	109.5	C12—C11—C14	115.08 (14)
H2A—C2—H2B	109.5	C12—C11—C10	117.72 (15)
C1—C2—H2C	109.5	C14—C11—C10	126.96 (15)
H2A—C2—H2C	109.5	N3—C12—C11	126.47 (17)
H2B—C2—H2C	109.5	N3—C12—H12	116.8
C1—C3—H3A	109.5	C11—C12—H12	116.8
C1—C3—H3B	109.5	N4—C13—N5	118.34 (16)
H3A—C3—H3B	109.5	N4—C13—N3	124.67 (14)
C1—C3—H3C	109.5	N5—C13—N3	116.98 (15)
H3A—C3—H3C	109.5	N4—C14—C11	119.68 (14)
H3B—C3—H3C	109.5	N4—C14—C15	114.77 (14)
C1—C4—H4A	109.5	C11—C14—C15	125.46 (14)
C1—C4—H4B	109.5	C16—C15—C20	116.87 (16)
H4A—C4—H4B	109.5	C16—C15—C14	121.81 (15)
C1—C4—H4C	109.5	C20—C15—C14	121.32 (15)
H4A—C4—H4C	109.5	C17—C16—C15	122.15 (19)
H4B—C4—H4C	109.5	C17—C16—H16	118.9
O2—C5—O1	125.84 (16)	C15—C16—H16	118.9
O2—C5—N1	123.43 (16)	C16—C17—C18	119.2 (2)
O1—C5—N1	110.66 (13)	C16—C17—H17	120.4
N1—C6—C7	110.82 (14)	C18—C17—H17	120.4
N1—C6—H6A	109.5	C19—C18—C17	120.32 (19)
C7—C6—H6A	109.5	C19—C18—H18	119.8
N1—C6—H6B	109.5	C17—C18—H18	119.8
C7—C6—H6B	109.5	C18—C19—C20	121.1 (2)
H6A—C6—H6B	108.1	C18—C19—H19	119.5
N2—C7—C6	110.82 (13)	C20—C19—H19	119.4
N2—C7—H7A	109.5	O3—C20—C19	117.65 (17)
C6—C7—H7A	109.5	O3—C20—C15	122.34 (16)
N2—C7—H7B	109.5	C19—C20—C15	119.98 (18)
C5—O1—C1—C4	63.7 (2)	C14—N4—C13—N5	179.31 (15)
C5—O1—C1—C3	−59.6 (2)	C14—N4—C13—N3	0.6 (2)
C5—O1—C1—C2	−179.57 (18)	C12—N3—C13—N4	2.4 (2)
C1—O1—C5—O2	−3.9 (3)	C12—N3—C13—N5	−176.31 (16)
C1—O1—C5—N1	178.86 (16)	C13—N4—C14—C11	−3.2 (2)
C6—N1—C5—O2	5.5 (3)	C13—N4—C14—C15	−179.82 (14)
C9—N1—C5—O2	168.93 (18)	C12—C11—C14—N4	2.5 (2)
C6—N1—C5—O1	−177.24 (15)	C10—C11—C14—N4	−171.82 (15)
C9—N1—C5—O1	−13.8 (2)	C12—C11—C14—C15	178.75 (15)
C5—N1—C6—C7	111.09 (18)	C10—C11—C14—C15	4.5 (3)
C9—N1—C6—C7	−54.2 (2)	N4—C14—C15—C16	−157.67 (17)
C8—N2—C7—C6	−58.01 (19)	C11—C14—C15—C16	25.9 (3)
C10—N2—C7—C6	179.42 (14)	N4—C14—C15—C20	23.2 (2)
N1—C6—C7—N2	55.5 (2)	C11—C14—C15—C20	−153.26 (16)
C7—N2—C8—C9	58.83 (18)	C20—C15—C16—C17	4.9 (3)
C10—N2—C8—C9	−177.15 (14)	C14—C15—C16—C17	−174.32 (19)
C5—N1—C9—C8	−110.40 (19)	C15—C16—C17—C18	0.1 (4)
C6—N1—C9—C8	54.0 (2)	C16—C17—C18—C19	−3.6 (4)
N2—C8—C9—N1	−56.0 (2)	C17—C18—C19—C20	1.9 (4)
C7—N2—C10—C11	−59.36 (19)	C18—C19—C20—O3	−178.7 (2)
C8—N2—C10—C11	178.07 (14)	C18—C19—C20—C15	3.3 (3)
N2—C10—C11—C12	98.42 (18)	C16—C15—C20—O3	175.57 (18)
N2—C10—C11—C14	−87.4 (2)	C14—C15—C20—O3	−5.2 (3)
C13—N3—C12—C11	−3.1 (3)	C16—C15—C20—C19	−6.5 (3)
C14—C11—C12—N3	0.8 (3)	C14—C15—C20—C19	172.72 (17)
C10—C11—C12—N3	175.61 (16)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H1O···N4	0.83 (1)	1.80 (2)	2.560 (2)	151 (3)
N5—H1N···N3i	0.86 (1)	2.19 (1)	3.054 (2)	179 (2)
N5—H2N···O3ii	0.86 (1)	2.29 (1)	3.139 (2)	169 (2)

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H1O⋯N4	0.83 (1)	1.80 (2)	2.560 (2)	151 (3)
N5—H1N⋯N3i	0.86 (1)	2.19 (1)	3.054 (2)	179 (2)
N5—H2N⋯O3ii	0.86 (1)	2.29 (1)	3.139 (2)	169 (2)

Symmetry codes: (i) ; (ii) .