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

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ISSN: 2056-9890

4-(3,4-Di­hydro-β-carbolin-1-yl)pyrimidin-2-amine

aDepartment of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
*Correspondence e-mail: seikweng@um.edu.my

(Received 19 February 2009; accepted 19 February 2009; online 25 February 2009)

The mol­ecule of accanthomine A, C15H13N5, is approximately planar, with the indolyl fused-ring and the pyrimidyl ring being twisted by 31.7 (1)° The amino group of the five-membered ring is an intramolecular hydrogen-bond donor to a nitro­gen acceptor of the pyrimide ring. The amino group of the pyrimide ring is a hydrogen-bond donor to the N atoms of adjacent mol­ecules. These hydrogen-bonding inter­actions give rise to a layered network with a 4.82 topology.

Related literature

The β-carboline fragment is found in the crystal structures of two compounds that show selective CDK4-cycli D1 inhibitory activity; see: García et al. (2006[García, M. D., Wilson, A. J., Emmerson, D. P. G., Jenkins, P. R., Mahale, S. & Chaudhuri, B. (2006). Org. Biomol. Chem. 4, 4478-4484.]). For related compounds, see: Costa et al. (2006[Costa, E. V., Phnheiro, M. L. B., Xavier, C. M., Silva, J. R. A., Amaral, A. C. F., Souza, A. D. L., Barison, A., Campos, F. R., Ferreira, A. G., Machado, G. M. C. & Leon, L. L. P. (2006). J. Nat. Prod. 69, 292-294.]); Kobayashi et al. (1995[Kobayashi, M., Chen, Y.-J., Aoki, S., In, Y., Ishida, T. & Kitagawa, I. (1995). Tetrahedron, 51, 3727-3736.]).

[Scheme 1]

Experimental

Crystal data
  • C15H13N5

  • Mr = 263.30

  • Monoclinic, P 21 /c

  • a = 11.4758 (2) Å

  • b = 12.6095 (2) Å

  • c = 8.9241 (2) Å

  • β = 102.116 (1)°

  • V = 1262.59 (4) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.09 mm−1

  • T = 120 K

  • 0.45 × 0.35 × 0.15 mm

Data collection
  • Bruker SMART APEX diffractometer

  • Absorption correction: none

  • 11840 measured reflections

  • 2905 independent reflections

  • 2485 reflections with I > 2σ(I)

  • Rint = 0.026

Refinement
  • R[F2 > 2σ(F2)] = 0.037

  • wR(F2) = 0.102

  • S = 1.02

  • 2905 reflections

  • 193 parameters

  • 3 restraints

  • H atoms treated by a mixture of independent and constrained refinement

  • Δρmax = 0.26 e Å−3

  • Δρmin = −0.23 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N1—H11⋯N2i 0.89 (2) 2.14 (2) 2.994 (3) 161 (3)
N1—H12⋯N5ii 0.91 (3) 2.25 (3) 3.138 (3) 165 (3)
N4—H4⋯N3 0.88 (2) 2.29 (3) 2.825 (3) 119 (2)
Symmetry codes: (i) [x, -y+{\script{3\over 2}}, z-{\script{1\over 2}}]; (ii) [-x+1, y+{\script{1\over 2}}, -z+{\script{3\over 2}}].

Data collection: APEX2 (Bruker, 2007[Bruker (2007). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2007[Bruker (2007). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: OLEX (Dolomanov et al., 2003[Dolomanov, O. V., Blake, A. J., Champness, N. R. & Schröder, M. (2003). J. Appl. Cryst. 36, 1283-1284.]) and X-SEED (Barbour, 2001[Barbour, L. J. (2001). J. Supramol. Chem. 1, 189-191.]); software used to prepare material for publication: publCIF (Westrip, 2009[Westrip, S. P. (2009). publCIF. In preparation.]).

Supporting information


Comment top

The molecule of Accanthomine A (I) is approximately planar; the amino group of the five-membered ring is hydrogen-bond donor to a nitrogen acceptor of the pyrimidyl ring (Fig. 1). The amino group of the pyrimidyl ring is a hydrogen-bond donor to the nitrogen atoms of adjacent molecules. The hydrogen bonding interactions give rise to a layer network with a 4.8 (2) topology (Fig. 2).

Related literature top

The β-carboline fragment is found in the crystal structures of two compounds that show selective CDK4-cycli D1 inhibitory activity; see: García et al. (2006). For related compounds, see: Costa et al. (2006); Kobayashi et al. (1995).

Experimental top

Litsea machilifolia was collected from the Mukim Telang Reserve, Kuala Lipis, Pahang. Specimens (KL5459) were deposited at the herbarium, Department of Chemistry, University of Malaya.

Dried and grounded leaves of Litsea machilifolia (2.1 kg) were extracted with dichloromethane. The dichloromethane extract was concentrated under reduced pressure to a volume of 500 ml and this was repeatedly extracted with 5% hydrocloric acid. The combined extracts were then basified with 10% ammonium hydroxide to a pH 11, and then re-extracted with dichloromethane. The crude alkaloid fraction was dark brown (4.0 g). A portion (4.0 g) was subjected to column chromatography on silica gel 60 GF254 by using a step gradient of dichloromethane and methanol. One of the fractions when further purified by CC with 100% dichloromethane afforded the pure compound, accanthomine A (8 mg), whose formulation was established by NMR spectroscopic analysis.

Refinement top

Carbon-bound H-atoms were placed in calculated positions (C–H 0.95–0.99 Å) and were included in the refinement in the riding model approximation, with U(H) set to 1.2U(C). The nitrogen-bound H-atoms were located in a difference Fourier map, and were refined with a distance restraint of N–H 0.88±0.01 Å; their temperature factors were freely refined.

Computing details top

Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX (Dolomanov et al., 2003) and X-SEED (Barbour, 2001); software used to prepare material for publication: publCIF (Westrip, 2009).

Figures top
[Figure 1] Fig. 1. Thermal ellipsoid plot (Barbour, 2001) of C15H13N3 at the 70% probability level. Hydrogen atoms are drawn as spheres of arbitrary radius.
[Figure 2] Fig. 2. Layer structure (Dolomanov et al., 2003).
4-(3,4-Dihydro-β-carbolin-1-yl)pyrimidin-2-amine top
Crystal data top
C15H13N5F(000) = 552
Mr = 263.30Dx = 1.385 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 4559 reflections
a = 11.4758 (2) Åθ = 2.4–28.3°
b = 12.6095 (2) ŵ = 0.09 mm1
c = 8.9241 (2) ÅT = 120 K
β = 102.116 (1)°Irregular block, light brown
V = 1262.59 (4) Å30.45 × 0.35 × 0.15 mm
Z = 4
Data collection top
Bruker SMART APEX
diffractometer
2485 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.026
Graphite monochromatorθmax = 27.5°, θmin = 1.8°
ω scansh = 1414
11840 measured reflectionsk = 1616
2905 independent reflectionsl = 1111
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)] = 0.037Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.102H atoms treated by a mixture of independent and constrained refinement
S = 1.02 w = 1/[σ2(Fo2) + (0.0591P)2 + 0.3611P]
where P = (Fo2 + 2Fc2)/3
2905 reflections(Δ/σ)max = 0.001
193 parametersΔρmax = 0.26 e Å3
3 restraintsΔρmin = 0.23 e Å3
Crystal data top
C15H13N5V = 1262.59 (4) Å3
Mr = 263.30Z = 4
Monoclinic, P21/cMo Kα radiation
a = 11.4758 (2) ŵ = 0.09 mm1
b = 12.6095 (2) ÅT = 120 K
c = 8.9241 (2) Å0.45 × 0.35 × 0.15 mm
β = 102.116 (1)°
Data collection top
Bruker SMART APEX
diffractometer
2485 reflections with I > 2σ(I)
11840 measured reflectionsRint = 0.026
2905 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0373 restraints
wR(F2) = 0.102H atoms treated by a mixture of independent and constrained refinement
S = 1.02Δρmax = 0.26 e Å3
2905 reflectionsΔρmin = 0.23 e Å3
193 parameters
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
N10.50153 (18)0.76301 (16)0.7128 (2)0.0209 (4)
N20.55480 (17)0.65191 (15)0.9213 (2)0.0187 (4)
N30.60199 (16)0.61005 (14)0.6777 (2)0.0165 (4)
N40.73723 (17)0.59739 (15)0.4478 (2)0.0180 (4)
C10.55292 (19)0.67210 (17)0.7718 (2)0.0163 (4)
C20.6123 (2)0.56393 (18)0.9781 (3)0.0194 (5)
H20.61720.54801.08330.023*
C30.6649 (2)0.49480 (17)0.8924 (3)0.0187 (5)
H30.70490.43250.93560.022*
C40.65609 (18)0.52161 (17)0.7390 (2)0.0159 (4)
C50.70796 (18)0.45156 (17)0.6351 (2)0.0162 (4)
C60.7651 (2)0.28242 (17)0.5636 (3)0.0199 (5)
H6A0.69770.26050.48090.024*
H6B0.79700.21760.62030.024*
C70.8626 (2)0.32896 (17)0.4896 (3)0.0185 (5)
H7A0.93930.33090.56500.022*
H7B0.87280.28430.40200.022*
C80.82678 (19)0.43888 (17)0.4355 (2)0.0165 (4)
C90.75008 (19)0.49495 (17)0.5047 (2)0.0162 (4)
C100.86494 (19)0.50915 (17)0.3305 (2)0.0168 (5)
C110.9446 (2)0.50053 (18)0.2302 (3)0.0203 (5)
H11A0.98630.43620.22330.024*
C120.9608 (2)0.58717 (19)0.1426 (3)0.0227 (5)
H12A1.01460.58230.07510.027*
C130.8991 (2)0.68278 (19)0.1512 (3)0.0218 (5)
H130.91110.74060.08790.026*
C140.8217 (2)0.69440 (18)0.2493 (3)0.0202 (5)
H140.78090.75930.25540.024*
C150.80577 (19)0.60715 (17)0.3395 (2)0.0173 (5)
N50.71831 (17)0.35226 (14)0.6694 (2)0.0188 (4)
H110.503 (3)0.778 (2)0.616 (2)0.030 (8)*
H120.448 (3)0.796 (2)0.759 (4)0.031 (8)*
H40.686 (2)0.643 (2)0.472 (3)0.031 (8)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0250 (10)0.0207 (10)0.0199 (10)0.0063 (8)0.0115 (8)0.0024 (7)
N20.0208 (9)0.0199 (9)0.0167 (9)0.0008 (7)0.0067 (7)0.0013 (7)
N30.0172 (9)0.0161 (9)0.0179 (9)0.0004 (7)0.0072 (7)0.0004 (7)
N40.0193 (9)0.0169 (9)0.0202 (9)0.0031 (7)0.0097 (7)0.0028 (7)
C10.0152 (10)0.0174 (10)0.0175 (10)0.0027 (8)0.0061 (8)0.0010 (8)
C20.0218 (11)0.0208 (11)0.0157 (10)0.0030 (9)0.0043 (8)0.0004 (8)
C30.0214 (11)0.0159 (10)0.0192 (11)0.0006 (8)0.0050 (9)0.0020 (8)
C40.0142 (9)0.0153 (10)0.0191 (11)0.0032 (8)0.0057 (8)0.0005 (8)
C50.0145 (9)0.0166 (10)0.0178 (10)0.0009 (8)0.0040 (8)0.0002 (8)
C60.0237 (11)0.0151 (10)0.0217 (11)0.0001 (8)0.0065 (9)0.0018 (8)
C70.0197 (10)0.0176 (10)0.0187 (10)0.0019 (8)0.0055 (8)0.0023 (8)
C80.0163 (10)0.0171 (10)0.0160 (10)0.0005 (8)0.0036 (8)0.0015 (8)
C90.0162 (10)0.0155 (10)0.0175 (10)0.0006 (8)0.0045 (8)0.0001 (8)
C100.0164 (10)0.0188 (10)0.0154 (10)0.0006 (8)0.0035 (8)0.0012 (8)
C110.0203 (11)0.0226 (11)0.0195 (11)0.0000 (9)0.0077 (9)0.0041 (8)
C120.0219 (11)0.0289 (12)0.0196 (11)0.0024 (9)0.0095 (9)0.0021 (9)
C130.0213 (11)0.0261 (12)0.0186 (11)0.0029 (9)0.0054 (9)0.0040 (9)
C140.0187 (10)0.0210 (11)0.0214 (11)0.0019 (9)0.0053 (9)0.0032 (9)
C150.0154 (10)0.0205 (11)0.0165 (10)0.0002 (8)0.0046 (8)0.0006 (8)
N50.0204 (9)0.0160 (9)0.0209 (9)0.0001 (7)0.0068 (7)0.0009 (7)
Geometric parameters (Å, º) top
N1—C11.345 (3)C6—C71.531 (3)
N1—H110.894 (17)C6—H6A0.9900
N1—H120.91 (3)C6—H6B0.9900
N2—C21.335 (3)C7—C81.497 (3)
N2—C11.354 (3)C7—H7A0.9900
N3—C41.336 (3)C7—H7B0.9900
N3—C11.354 (3)C8—C91.373 (3)
N4—C151.374 (3)C8—C101.424 (3)
N4—C91.384 (3)C10—C111.411 (3)
N4—H40.883 (17)C10—C151.420 (3)
C2—C31.380 (3)C11—C121.379 (3)
C2—H20.9500C11—H11A0.9500
C3—C41.393 (3)C12—C131.408 (3)
C3—H30.9500C12—H12A0.9500
C4—C51.492 (3)C13—C141.380 (3)
C5—N51.288 (3)C13—H130.9500
C5—C91.457 (3)C14—C151.398 (3)
C6—N51.472 (3)C14—H140.9500
C1—N1—H11117.6 (19)C8—C7—H7A110.0
C1—N1—H12120.0 (19)C6—C7—H7A110.0
H11—N1—H12120 (3)C8—C7—H7B110.0
C2—N2—C1115.78 (18)C6—C7—H7B110.0
C4—N3—C1116.49 (18)H7A—C7—H7B108.4
C15—N4—C9108.00 (17)C9—C8—C10106.88 (19)
C15—N4—H4128 (2)C9—C8—C7119.37 (19)
C9—N4—H4123 (2)C10—C8—C7133.41 (19)
N1—C1—N2117.46 (19)C8—C9—N4110.16 (18)
N1—C1—N3117.05 (19)C8—C9—C5121.2 (2)
N2—C1—N3125.5 (2)N4—C9—C5127.99 (19)
N2—C2—C3123.6 (2)C11—C10—C15119.0 (2)
N2—C2—H2118.2C11—C10—C8134.3 (2)
C3—C2—H2118.2C15—C10—C8106.69 (18)
C2—C3—C4116.2 (2)C12—C11—C10118.7 (2)
C2—C3—H3121.9C12—C11—H11A120.6
C4—C3—H3121.9C10—C11—H11A120.6
N3—C4—C3122.46 (19)C11—C12—C13121.2 (2)
N3—C4—C5116.83 (18)C11—C12—H12A119.4
C3—C4—C5120.71 (19)C13—C12—H12A119.4
N5—C5—C9121.66 (19)C14—C13—C12121.6 (2)
N5—C5—C4117.19 (19)C14—C13—H13119.2
C9—C5—C4121.09 (19)C12—C13—H13119.2
N5—C6—C7116.45 (18)C13—C14—C15117.5 (2)
N5—C6—H6A108.2C13—C14—H14121.3
C7—C6—H6A108.2C15—C14—H14121.3
N5—C6—H6B108.2N4—C15—C14129.7 (2)
C7—C6—H6B108.2N4—C15—C10108.25 (18)
H6A—C6—H6B107.3C14—C15—C10122.0 (2)
C8—C7—C6108.57 (17)C5—N5—C6117.20 (18)
C2—N2—C1—N1176.44 (19)C4—C5—C9—C8161.4 (2)
C2—N2—C1—N31.3 (3)N5—C5—C9—N4174.8 (2)
C4—N3—C1—N1177.94 (19)C4—C5—C9—N48.1 (3)
C4—N3—C1—N20.2 (3)C9—C8—C10—C11177.9 (2)
C1—N2—C2—C31.5 (3)C7—C8—C10—C114.9 (4)
N2—C2—C3—C40.4 (3)C9—C8—C10—C151.1 (2)
C1—N3—C4—C31.5 (3)C7—C8—C10—C15174.0 (2)
C1—N3—C4—C5178.65 (18)C15—C10—C11—C121.1 (3)
C2—C3—C4—N31.3 (3)C8—C10—C11—C12179.9 (2)
C2—C3—C4—C5178.92 (19)C10—C11—C12—C130.3 (3)
N3—C4—C5—N5154.0 (2)C11—C12—C13—C141.2 (4)
C3—C4—C5—N526.2 (3)C12—C13—C14—C150.6 (3)
N3—C4—C5—C928.7 (3)C9—N4—C15—C14179.5 (2)
C3—C4—C5—C9151.1 (2)C9—N4—C15—C101.2 (2)
N5—C6—C7—C844.9 (3)C13—C14—C15—N4178.4 (2)
C6—C7—C8—C925.0 (3)C13—C14—C15—C100.9 (3)
C6—C7—C8—C10162.7 (2)C11—C10—C15—N4177.72 (19)
C10—C8—C9—N40.4 (3)C8—C10—C15—N41.4 (2)
C7—C8—C9—N4174.49 (18)C11—C10—C15—C141.7 (3)
C10—C8—C9—C5170.84 (19)C8—C10—C15—C14179.2 (2)
C7—C8—C9—C53.3 (3)C9—C5—N5—C65.1 (3)
C15—N4—C9—C80.5 (3)C4—C5—N5—C6177.67 (18)
C15—N4—C9—C5171.0 (2)C7—C6—N5—C536.6 (3)
N5—C5—C9—C815.7 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H11···N2i0.89 (2)2.14 (2)2.994 (3)161 (3)
N1—H12···N5ii0.91 (3)2.25 (3)3.138 (3)165 (3)
N4—H4···N30.88 (2)2.29 (3)2.825 (3)119 (2)
Symmetry codes: (i) x, y+3/2, z1/2; (ii) x+1, y+1/2, z+3/2.

Experimental details

Crystal data
Chemical formulaC15H13N5
Mr263.30
Crystal system, space groupMonoclinic, P21/c
Temperature (K)120
a, b, c (Å)11.4758 (2), 12.6095 (2), 8.9241 (2)
β (°) 102.116 (1)
V3)1262.59 (4)
Z4
Radiation typeMo Kα
µ (mm1)0.09
Crystal size (mm)0.45 × 0.35 × 0.15
Data collection
DiffractometerBruker SMART APEX
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
11840, 2905, 2485
Rint0.026
(sin θ/λ)max1)0.650
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.037, 0.102, 1.02
No. of reflections2905
No. of parameters193
No. of restraints3
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.26, 0.23

Computer programs: APEX2 (Bruker, 2007), SAINT (Bruker, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), OLEX (Dolomanov et al., 2003) and X-SEED (Barbour, 2001), publCIF (Westrip, 2009).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H11···N2i0.89 (2)2.14 (2)2.994 (3)161 (3)
N1—H12···N5ii0.91 (3)2.25 (3)3.138 (3)165 (3)
N4—H4···N30.88 (2)2.29 (3)2.825 (3)119 (2)
Symmetry codes: (i) x, y+3/2, z1/2; (ii) x+1, y+1/2, z+3/2.
 

Acknowledgements

We thank the University of Malaya for supporting this study (by PPP/PS231/2008B and Science Fund 12–02-03–2063).

References

First citationBarbour, L. J. (2001). J. Supramol. Chem. 1, 189–191.  CrossRef CAS Google Scholar
First citationBruker (2007). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationCosta, E. V., Phnheiro, M. L. B., Xavier, C. M., Silva, J. R. A., Amaral, A. C. F., Souza, A. D. L., Barison, A., Campos, F. R., Ferreira, A. G., Machado, G. M. C. & Leon, L. L. P. (2006). J. Nat. Prod. 69, 292–294.  Web of Science CrossRef PubMed CAS Google Scholar
First citationDolomanov, O. V., Blake, A. J., Champness, N. R. & Schröder, M. (2003). J. Appl. Cryst. 36, 1283–1284.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationGarcía, M. D., Wilson, A. J., Emmerson, D. P. G., Jenkins, P. R., Mahale, S. & Chaudhuri, B. (2006). Org. Biomol. Chem. 4, 4478–4484.  Web of Science PubMed Google Scholar
First citationKobayashi, M., Chen, Y.-J., Aoki, S., In, Y., Ishida, T. & Kitagawa, I. (1995). Tetrahedron, 51, 3727–3736.  CSD CrossRef CAS Web of Science Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationWestrip, S. P. (2009). publCIF. In preparation.  Google Scholar

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