organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2414-3146

4-Amino-6-(piperidin-1-yl)pyrimidine-5-carbo­nitrile

aDepartment of studies in Chemistry, Bangalore University, Jnana Bharathi Campus, Bangalore-560 056, Karnataka, India
*Correspondence e-mail: noorsb05@gmail.com

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 12 March 2020; accepted 16 March 2020; online 17 March 2020)

In the title compound, C10H13N5, the piperidine ring adopts a chair conformation with the exocyclic N—C bond in an axial orientation, and the dihedral angle between the mean planes of piperidine and pyrimidine rings is 49.57 (11)°. A short intra­molecular C—H⋯N contact generates an S(7) ring. In the crystal, N—H⋯N hydrogen bonds link the mol­ecules into (100) sheets and a weak aromatic π-π stacking inter­action is observed [centroid–centroid separation = 3.5559 (11) Å] between inversion-related pyrimidine rings.

3D view (loading...)
[Scheme 3D1]
Chemical scheme
[Scheme 1]

Structure description

Pyrimidine derivatives exhibit a broad spectrum of biological activities such as GPR119 agonists (Fang et al., 2019[Fang, Y., Xiong, L., Hu, J., Zhang, S., Xie, S., Tu, L., Wan, Y., Jin, Y., Li, X., Hu, S. & Yang, Z. (2019). Bioorg. Chem. 86, 103-111.]), VEGFR-2 tyrosine kinase inhibitors (Sun et al., 2018[Sun, W., Hu, S., Fang, S. & Yan, H. (2018). Bioorg. Chem. 78, 393-405.]) and anti­tumor activity (Hassan et al., 2017[Hassan, A. S., Mady, M. F., Awad, H. M. & Hafez, T. S. (2017). Chin. Chem. Lett. 28, 388-393.]). As part of our studies in this area, we now describe the synthesis and structure of the title compound.

The title compound crystallizes with one mol­ecule in the asymmetric unit (Fig. 1[link]). The piperidine ring adopts a chair conformation, with atoms N3 and C7 displaced from the mean plane of the other four atoms (C5/C6/C8/C9) by −0.2472 (2) and 0.2133 (3) Å, respectively. The exocyclic N3—C4 bond has an axial orientation and the dihedral angle between the piperidine ring mean plane (all atoms) and the pyrimidine ring is 49.57 (11)°. A short intra­molecular C9—H9B⋯N5 contact generates an S(7) ring.

[Figure 1]
Figure 1
The mol­ecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level. The short C—H⋯N contact is indicated by a double-dashed line.

In the crystal, N4—H4A⋯N1 hydrogen bonds (Table 1[link]) link the mol­ecules into inversion dimers characterized by an R22(8) graph set motif (Fig. 2[link]) and N4—H4B⋯N5 hydrogen bonds link the dimers into (100) sheets. The packing also features ππ stacking inter­actions between inversion-related pyrimidine rings at a centroid–centroid distance of 3.5559 (11) Å (Fig. 3[link]).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N4—H4A⋯N1i 0.86 2.12 2.983 (2) 173
N4—H4B⋯N5ii 0.86 2.44 3.115 (3) 135
C9—H9B⋯N5 0.97 2.61 3.484 (1) 148
Symmetry codes: (i) -x+2, -y, -z+1; (ii) [x, -y+{\script{1\over 2}}, z+{\script{1\over 2}}].
[Figure 2]
Figure 2
Unit-cell packing of the title compound showing N—H⋯N inter­actions as dotted green and purple lines. H atoms not involved in hydrogen bonding have been excluded.
[Figure 3]
Figure 3
A fragment of the packing depicting the ππ inter­action as a dashed line.

Synthesis and crystallization

A mixture of 4-amino-6-chloro-pyrimidine-5-carbo­nitrile 1.0 g (0.0065 mol) and piperidine (2.75 g, 0.0325 mol) was refluxed in 20 ml of ethanol for 6 h. The reaction mixture was then cooled and stirred for 2 h at room temperature. The solid obtained was filtered, washed with ethanol and dried giving 0.98 g of white solid (yield 74%), which was recrystallized from acetone solution to obtain colourless blocks of the title compound. IR (ν, cm−1: 3426, 3308 (NH), 2190 (C=N), 1646 (C=N), 1223 (CN). 1H NMR (400 MHz DMSO-d6): δ 8.01 (s, 1H, pyrimidine CH), 7.21 (br. s, 1 N, NH2), 3.76 (t, 2H, CH2), 1.73–1.48 (m, 6H, 3CH2). 13C NMR (DMSO-d6): δ 168.5, 164.3, 159.9, 118.1, 58.9, 26.8, 24.9.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link].

Table 2
Experimental details

Crystal data
Chemical formula C10H13N5
Mr 203.25
Crystal system, space group Monoclinic, P21/c
Temperature (K) 446
a, b, c (Å) 10.7335 (9), 12.4005 (10), 7.9206 (6)
β (°) 93.654 (4)
V3) 1052.09 (15)
Z 4
Radiation type Mo Kα
μ (mm−1) 0.08
Crystal size (mm) 0.18 × 0.16 × 0.15
 
Data collection
Diffractometer Bruker SMART APEX CCD
Absorption correction Multi-scan (SADABS; Bruker, 1998[Bruker. (1998). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
No. of measured, independent and observed [I > 2σ(I)] reflections 12900, 1855, 1452
Rint 0.034
(sin θ/λ)max−1) 0.595
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.050, 0.180, 1.16
No. of reflections 1855
No. of parameters 136
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.21, −0.28
Computer programs: SMART and SAINT (Bruker, 1998[Bruker. (1998). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL2018 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]) and ORTEP-3 for Windows (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]).

Structural data


Computing details top

Data collection: SMART (Bruker, 1998); cell refinement: SAINT (Bruker, 1998); data reduction: SAINT (Bruker, 1998); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: SHELXL2018 (Sheldrick, 2015).

4-Amino-6-(piperidin-1-yl)pyrimidine-5-carbonitrile top
Crystal data top
C10H13N5F(000) = 432
Mr = 203.25Dx = 1.283 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 10.7335 (9) ÅCell parameters from 1855 reflections
b = 12.4005 (10) Åθ = 1.9–25.0°
c = 7.9206 (6) ŵ = 0.08 mm1
β = 93.654 (4)°T = 446 K
V = 1052.09 (15) Å3Block, colourless
Z = 40.18 × 0.16 × 0.15 mm
Data collection top
Bruker SMART APEX CCD
diffractometer
1452 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.034
ω scansθmax = 25.0°, θmin = 1.9°
Absorption correction: multi-scan
(SADABS; Bruker, 1998)
h = 1212
k = 1414
12900 measured reflectionsl = 98
1855 independent reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.050Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.180H-atom parameters constrained
S = 1.16 w = 1/[σ2(Fo2) + (0.1087P)2 + 0.0972P]
where P = (Fo2 + 2Fc2)/3
1855 reflections(Δ/σ)max < 0.001
136 parametersΔρmax = 0.21 e Å3
0 restraintsΔρmin = 0.28 e Å3
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. H atoms were placed at calculated positions in the riding-model approximation, with N—H = 0.86 Å and C—H = 0.93 0.96 and 0.97 Å for aromatic, methyl and methine H atoms, respectively. The constraint Uiso(H) = 1.5Ueq(C) for methyl H atoms and 1.2Ueq(carrier) otherwise was applied.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.81607 (15)0.03767 (13)0.1080 (2)0.0523 (5)
C20.88239 (16)0.02327 (14)0.2655 (2)0.0549 (5)
C40.82310 (16)0.04487 (14)0.0150 (3)0.0578 (5)
N10.95761 (14)0.06277 (12)0.2958 (2)0.0637 (5)
N30.75761 (15)0.04668 (14)0.1662 (2)0.0722 (5)
C100.76188 (17)0.14099 (15)0.0789 (2)0.0574 (5)
N40.87641 (16)0.09400 (13)0.3914 (2)0.0702 (5)
H4A0.9191230.0834410.4855170.084*
H4B0.8298330.1502000.3784990.084*
N20.90227 (15)0.12859 (13)0.0178 (3)0.0691 (5)
N50.72548 (18)0.22727 (14)0.0646 (3)0.0782 (6)
C30.96377 (18)0.12964 (16)0.1669 (3)0.0691 (6)
H31.0201830.1861030.1840800.083*
C80.5344 (2)0.0579 (2)0.2263 (3)0.0902 (8)
H8A0.4609850.0166190.2634510.108*
H8B0.5204690.0879030.1159680.108*
C50.7794 (2)0.1314 (2)0.2914 (3)0.0855 (7)
H5A0.8549030.1707650.2569530.103*
H5B0.7908070.0986120.4005220.103*
C60.6712 (2)0.2074 (2)0.3063 (3)0.0802 (7)
H6A0.6654020.2455040.2000850.096*
H6B0.6848410.2603380.3934120.096*
C90.6452 (2)0.01582 (19)0.2108 (3)0.0776 (6)
H9A0.6539080.0528500.3173130.093*
H9B0.6332970.0695920.1243870.093*
C70.5513 (3)0.1489 (3)0.3494 (4)0.1092 (10)
H7A0.4819120.1988460.3458550.131*
H7B0.5517400.1202340.4632970.131*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0429 (9)0.0413 (9)0.0733 (12)0.0013 (7)0.0095 (8)0.0058 (8)
C20.0461 (9)0.0421 (9)0.0771 (13)0.0017 (7)0.0087 (8)0.0062 (8)
C40.0398 (9)0.0528 (10)0.0819 (13)0.0079 (7)0.0118 (8)0.0037 (9)
N10.0569 (10)0.0484 (9)0.0858 (12)0.0083 (7)0.0045 (8)0.0039 (8)
N30.0522 (10)0.0749 (12)0.0894 (13)0.0009 (8)0.0024 (8)0.0172 (9)
C100.0547 (10)0.0478 (11)0.0695 (12)0.0035 (8)0.0036 (8)0.0065 (8)
N40.0774 (11)0.0569 (10)0.0753 (12)0.0180 (8)0.0036 (8)0.0008 (8)
N20.0502 (9)0.0555 (10)0.1022 (14)0.0033 (7)0.0089 (9)0.0119 (9)
N50.0879 (13)0.0496 (10)0.0955 (15)0.0058 (9)0.0071 (10)0.0081 (8)
C30.0503 (11)0.0509 (11)0.1066 (17)0.0086 (8)0.0076 (10)0.0009 (11)
C80.0557 (13)0.118 (2)0.0950 (17)0.0059 (12)0.0105 (11)0.0233 (15)
C50.0727 (14)0.1028 (19)0.0825 (16)0.0020 (13)0.0154 (11)0.0248 (14)
C60.0959 (17)0.0833 (15)0.0607 (13)0.0066 (13)0.0000 (11)0.0158 (10)
C90.0793 (15)0.0737 (14)0.0787 (15)0.0076 (11)0.0039 (11)0.0027 (11)
C70.0790 (17)0.137 (3)0.109 (2)0.0090 (16)0.0162 (14)0.0462 (19)
Geometric parameters (Å, º) top
C1—C21.408 (3)C8—C91.499 (3)
C1—C41.418 (3)C8—C71.510 (4)
C1—C101.420 (3)C8—H8A0.9700
C2—N41.332 (2)C8—H8B0.9700
C2—N11.350 (2)C5—C61.495 (3)
C4—N31.350 (3)C5—H5A0.9700
C4—N21.356 (3)C5—H5B0.9700
N1—C31.321 (3)C6—C71.498 (4)
N3—C91.459 (3)C6—H6A0.9700
N3—C51.474 (3)C6—H6B0.9700
C10—N51.142 (2)C9—H9A0.9700
N4—H4A0.8600C9—H9B0.9700
N4—H4B0.8600C7—H7A0.9700
N2—C31.316 (3)C7—H7B0.9700
C3—H30.9300
C2—C1—C4118.10 (16)H8A—C8—H8B107.8
C2—C1—C10115.91 (16)N3—C5—C6110.29 (18)
C4—C1—C10125.39 (18)N3—C5—H5A109.6
N4—C2—N1116.35 (18)C6—C5—H5A109.6
N4—C2—C1122.27 (16)N3—C5—H5B109.6
N1—C2—C1121.37 (17)C6—C5—H5B109.6
N3—C4—N2116.21 (18)H5A—C5—H5B108.1
N3—C4—C1125.02 (18)C5—C6—C7111.4 (2)
N2—C4—C1118.76 (19)C5—C6—H6A109.4
C3—N1—C2114.68 (18)C7—C6—H6A109.4
C4—N3—C9125.62 (18)C5—C6—H6B109.4
C4—N3—C5120.85 (19)C7—C6—H6B109.4
C9—N3—C5112.34 (18)H6A—C6—H6B108.0
N5—C10—C1174.5 (2)N3—C9—C8109.6 (2)
C2—N4—H4A120.0N3—C9—H9A109.8
C2—N4—H4B120.0C8—C9—H9A109.8
H4A—N4—H4B120.0N3—C9—H9B109.8
C3—N2—C4116.86 (17)C8—C9—H9B109.8
N2—C3—N1129.86 (18)H9A—C9—H9B108.2
N2—C3—H3115.1C6—C7—C8110.6 (2)
N1—C3—H3115.1C6—C7—H7A109.5
C9—C8—C7112.4 (2)C8—C7—H7A109.5
C9—C8—H8A109.1C6—C7—H7B109.5
C7—C8—H8A109.1C8—C7—H7B109.5
C9—C8—H8B109.1H7A—C7—H7B108.1
C7—C8—H8B109.1
C4—C1—C2—N4176.67 (15)C1—C4—N3—C5174.72 (17)
C10—C1—C2—N411.7 (2)N3—C4—N2—C3177.91 (17)
C4—C1—C2—N14.5 (3)C1—C4—N2—C33.0 (3)
C10—C1—C2—N1167.09 (16)C4—N2—C3—N12.8 (3)
C2—C1—C4—N3174.67 (16)C2—N1—C3—N24.6 (3)
C10—C1—C4—N314.6 (3)C4—N3—C5—C6108.9 (2)
C2—C1—C4—N26.3 (3)C9—N3—C5—C659.3 (3)
C10—C1—C4—N2164.43 (16)N3—C5—C6—C755.9 (3)
N4—C2—N1—C3178.31 (16)C4—N3—C9—C8109.3 (2)
C1—C2—N1—C30.6 (3)C5—N3—C9—C858.3 (3)
N2—C4—N3—C9162.23 (19)C7—C8—C9—N355.0 (3)
C1—C4—N3—C918.7 (3)C5—C6—C7—C852.9 (3)
N2—C4—N3—C54.3 (3)C9—C8—C7—C652.8 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N4—H4A···N1i0.862.122.983 (2)173
N4—H4B···N5ii0.862.443.115 (3)135
C9—H9B···N50.972.613.484 (1)148
Symmetry codes: (i) x+2, y, z+1; (ii) x, y+1/2, z+1/2.
 

References

First citationBruker. (1998). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationFang, Y., Xiong, L., Hu, J., Zhang, S., Xie, S., Tu, L., Wan, Y., Jin, Y., Li, X., Hu, S. & Yang, Z. (2019). Bioorg. Chem. 86, 103–111.  CrossRef CAS PubMed Google Scholar
First citationFarrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationHassan, A. S., Mady, M. F., Awad, H. M. & Hafez, T. S. (2017). Chin. Chem. Lett. 28, 388–393.  CrossRef CAS Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationSun, W., Hu, S., Fang, S. & Yan, H. (2018). Bioorg. Chem. 78, 393–405.  CrossRef CAS PubMed Google Scholar

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