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

Mukhtar, M.R.; Zainal Abidin, A.; Awang, K.; Hadi, A.H.A.; Ng, S.W.

doi:10.1107/S160053680900600X

organic compounds

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ISSN: 2056-9890

Volume 65| Part 3| March 2009| Page o594

doi:10.1107/S160053680900600X

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

Mat Ropi Mukhtar,^a Anissuhailin Zainal Abidin,^a Khalijah Awang,^a A. Hamid A. Hadi ^a and Seik Weng Ng ^a ^*

^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 ). For related compounds, see: Costa et al. (2006 ); Kobayashi et al. (1995 ).

Experimental

Crystal data

C₁₅H₁₃N₅
M_r = 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)
R_int = 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
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.23 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	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 ); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT; 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 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053680900600X/hg2480sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S160053680900600X/hg2480Isup2.hkl

checkCIF report

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.

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

	Fig. 1. Thermal ellipsoid plot (Barbour, 2001) of C₁₅H₁₃N₃ at the 70% probability level. Hydrogen atoms are drawn as spheres of arbitrary radius.
	Fig. 2. Layer structure (Dolomanov et al., 2003).

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

Crystal data top

C₁₅H₁₃N₅	F(000) = 552
M_r = 263.30	D_x = 1.385 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 4559 reflections
a = 11.4758 (2) Å	θ = 2.4–28.3°
b = 12.6095 (2) Å	µ = 0.09 mm⁻¹
c = 8.9241 (2) Å	T = 120 K
β = 102.116 (1)°	Irregular block, light brown
V = 1262.59 (4) Å³	0.45 × 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 tube	R_int = 0.026
Graphite monochromator	θ_max = 27.5°, θ_min = 1.8°
ω scans	h = −14→14
11840 measured reflections	k = −16→16
2905 independent reflections	l = −11→11

Refinement top

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)] = 0.037	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.102	H atoms treated by a mixture of independent and constrained refinement
S = 1.02	w = 1/[σ²(F_o²) + (0.0591P)² + 0.3611P] where P = (F_o² + 2F_c²)/3
2905 reflections	(Δ/σ)_max = 0.001
193 parameters	Δρ_max = 0.26 e Å⁻³
3 restraints	Δρ_min = −0.23 e Å⁻³

Crystal data top

C₁₅H₁₃N₅	V = 1262.59 (4) Å³
M_r = 263.30	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 11.4758 (2) Å	µ = 0.09 mm⁻¹
b = 12.6095 (2) Å	T = 120 K
c = 8.9241 (2) Å	0.45 × 0.35 × 0.15 mm
β = 102.116 (1)°

Data collection top

Bruker SMART APEX diffractometer	2485 reflections with I > 2σ(I)
11840 measured reflections	R_int = 0.026
2905 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.037	3 restraints
wR(F²) = 0.102	H atoms treated by a mixture of independent and constrained refinement
S = 1.02	Δρ_max = 0.26 e Å⁻³
2905 reflections	Δρ_min = −0.23 e Å⁻³
193 parameters

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
N1	0.50153 (18)	0.76301 (16)	0.7128 (2)	0.0209 (4)
N2	0.55480 (17)	0.65191 (15)	0.9213 (2)	0.0187 (4)
N3	0.60199 (16)	0.61005 (14)	0.6777 (2)	0.0165 (4)
N4	0.73723 (17)	0.59739 (15)	0.4478 (2)	0.0180 (4)
C1	0.55292 (19)	0.67210 (17)	0.7718 (2)	0.0163 (4)
C2	0.6123 (2)	0.56393 (18)	0.9781 (3)	0.0194 (5)
H2	0.6172	0.5480	1.0833	0.023*
C3	0.6649 (2)	0.49480 (17)	0.8924 (3)	0.0187 (5)
H3	0.7049	0.4325	0.9356	0.022*
C4	0.65609 (18)	0.52161 (17)	0.7390 (2)	0.0159 (4)
C5	0.70796 (18)	0.45156 (17)	0.6351 (2)	0.0162 (4)
C6	0.7651 (2)	0.28242 (17)	0.5636 (3)	0.0199 (5)
H6A	0.6977	0.2605	0.4809	0.024*
H6B	0.7970	0.2176	0.6203	0.024*
C7	0.8626 (2)	0.32896 (17)	0.4896 (3)	0.0185 (5)
H7A	0.9393	0.3309	0.5650	0.022*
H7B	0.8728	0.2843	0.4020	0.022*
C8	0.82678 (19)	0.43888 (17)	0.4355 (2)	0.0165 (4)
C9	0.75008 (19)	0.49495 (17)	0.5047 (2)	0.0162 (4)
C10	0.86494 (19)	0.50915 (17)	0.3305 (2)	0.0168 (5)
C11	0.9446 (2)	0.50053 (18)	0.2302 (3)	0.0203 (5)
H11A	0.9863	0.4362	0.2233	0.024*
C12	0.9608 (2)	0.58717 (19)	0.1426 (3)	0.0227 (5)
H12A	1.0146	0.5823	0.0751	0.027*
C13	0.8991 (2)	0.68278 (19)	0.1512 (3)	0.0218 (5)
H13	0.9111	0.7406	0.0879	0.026*
C14	0.8217 (2)	0.69440 (18)	0.2493 (3)	0.0202 (5)
H14	0.7809	0.7593	0.2554	0.024*
C15	0.80577 (19)	0.60715 (17)	0.3395 (2)	0.0173 (5)
N5	0.71831 (17)	0.35226 (14)	0.6694 (2)	0.0188 (4)
H11	0.503 (3)	0.778 (2)	0.616 (2)	0.030 (8)*
H12	0.448 (3)	0.796 (2)	0.759 (4)	0.031 (8)*
H4	0.686 (2)	0.643 (2)	0.472 (3)	0.031 (8)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0250 (10)	0.0207 (10)	0.0199 (10)	0.0063 (8)	0.0115 (8)	0.0024 (7)
N2	0.0208 (9)	0.0199 (9)	0.0167 (9)	−0.0008 (7)	0.0067 (7)	−0.0013 (7)
N3	0.0172 (9)	0.0161 (9)	0.0179 (9)	−0.0004 (7)	0.0072 (7)	−0.0004 (7)
N4	0.0193 (9)	0.0169 (9)	0.0202 (9)	0.0031 (7)	0.0097 (7)	0.0028 (7)
C1	0.0152 (10)	0.0174 (10)	0.0175 (10)	−0.0027 (8)	0.0061 (8)	−0.0010 (8)
C2	0.0218 (11)	0.0208 (11)	0.0157 (10)	−0.0030 (9)	0.0043 (8)	0.0004 (8)
C3	0.0214 (11)	0.0159 (10)	0.0192 (11)	−0.0006 (8)	0.0050 (9)	0.0020 (8)
C4	0.0142 (9)	0.0153 (10)	0.0191 (11)	−0.0032 (8)	0.0057 (8)	−0.0005 (8)
C5	0.0145 (9)	0.0166 (10)	0.0178 (10)	−0.0009 (8)	0.0040 (8)	0.0002 (8)
C6	0.0237 (11)	0.0151 (10)	0.0217 (11)	−0.0001 (8)	0.0065 (9)	−0.0018 (8)
C7	0.0197 (10)	0.0176 (10)	0.0187 (10)	0.0019 (8)	0.0055 (8)	−0.0023 (8)
C8	0.0163 (10)	0.0171 (10)	0.0160 (10)	−0.0005 (8)	0.0036 (8)	−0.0015 (8)
C9	0.0162 (10)	0.0155 (10)	0.0175 (10)	−0.0006 (8)	0.0045 (8)	0.0001 (8)
C10	0.0164 (10)	0.0188 (10)	0.0154 (10)	−0.0006 (8)	0.0035 (8)	−0.0012 (8)
C11	0.0203 (11)	0.0226 (11)	0.0195 (11)	0.0000 (9)	0.0077 (9)	−0.0041 (8)
C12	0.0219 (11)	0.0289 (12)	0.0196 (11)	−0.0024 (9)	0.0095 (9)	−0.0021 (9)
C13	0.0213 (11)	0.0261 (12)	0.0186 (11)	−0.0029 (9)	0.0054 (9)	0.0040 (9)
C14	0.0187 (10)	0.0210 (11)	0.0214 (11)	0.0019 (9)	0.0053 (9)	0.0032 (9)
C15	0.0154 (10)	0.0205 (11)	0.0165 (10)	−0.0002 (8)	0.0046 (8)	−0.0006 (8)
N5	0.0204 (9)	0.0160 (9)	0.0209 (9)	−0.0001 (7)	0.0068 (7)	−0.0009 (7)

Geometric parameters (Å, º) top

N1—C1	1.345 (3)	C6—C7	1.531 (3)
N1—H11	0.894 (17)	C6—H6A	0.9900
N1—H12	0.91 (3)	C6—H6B	0.9900
N2—C2	1.335 (3)	C7—C8	1.497 (3)
N2—C1	1.354 (3)	C7—H7A	0.9900
N3—C4	1.336 (3)	C7—H7B	0.9900
N3—C1	1.354 (3)	C8—C9	1.373 (3)
N4—C15	1.374 (3)	C8—C10	1.424 (3)
N4—C9	1.384 (3)	C10—C11	1.411 (3)
N4—H4	0.883 (17)	C10—C15	1.420 (3)
C2—C3	1.380 (3)	C11—C12	1.379 (3)
C2—H2	0.9500	C11—H11A	0.9500
C3—C4	1.393 (3)	C12—C13	1.408 (3)
C3—H3	0.9500	C12—H12A	0.9500
C4—C5	1.492 (3)	C13—C14	1.380 (3)
C5—N5	1.288 (3)	C13—H13	0.9500
C5—C9	1.457 (3)	C14—C15	1.398 (3)
C6—N5	1.472 (3)	C14—H14	0.9500

C1—N1—H11	117.6 (19)	C8—C7—H7A	110.0
C1—N1—H12	120.0 (19)	C6—C7—H7A	110.0
H11—N1—H12	120 (3)	C8—C7—H7B	110.0
C2—N2—C1	115.78 (18)	C6—C7—H7B	110.0
C4—N3—C1	116.49 (18)	H7A—C7—H7B	108.4
C15—N4—C9	108.00 (17)	C9—C8—C10	106.88 (19)
C15—N4—H4	128 (2)	C9—C8—C7	119.37 (19)
C9—N4—H4	123 (2)	C10—C8—C7	133.41 (19)
N1—C1—N2	117.46 (19)	C8—C9—N4	110.16 (18)
N1—C1—N3	117.05 (19)	C8—C9—C5	121.2 (2)
N2—C1—N3	125.5 (2)	N4—C9—C5	127.99 (19)
N2—C2—C3	123.6 (2)	C11—C10—C15	119.0 (2)
N2—C2—H2	118.2	C11—C10—C8	134.3 (2)
C3—C2—H2	118.2	C15—C10—C8	106.69 (18)
C2—C3—C4	116.2 (2)	C12—C11—C10	118.7 (2)
C2—C3—H3	121.9	C12—C11—H11A	120.6
C4—C3—H3	121.9	C10—C11—H11A	120.6
N3—C4—C3	122.46 (19)	C11—C12—C13	121.2 (2)
N3—C4—C5	116.83 (18)	C11—C12—H12A	119.4
C3—C4—C5	120.71 (19)	C13—C12—H12A	119.4
N5—C5—C9	121.66 (19)	C14—C13—C12	121.6 (2)
N5—C5—C4	117.19 (19)	C14—C13—H13	119.2
C9—C5—C4	121.09 (19)	C12—C13—H13	119.2
N5—C6—C7	116.45 (18)	C13—C14—C15	117.5 (2)
N5—C6—H6A	108.2	C13—C14—H14	121.3
C7—C6—H6A	108.2	C15—C14—H14	121.3
N5—C6—H6B	108.2	N4—C15—C14	129.7 (2)
C7—C6—H6B	108.2	N4—C15—C10	108.25 (18)
H6A—C6—H6B	107.3	C14—C15—C10	122.0 (2)
C8—C7—C6	108.57 (17)	C5—N5—C6	117.20 (18)

C2—N2—C1—N1	−176.44 (19)	C4—C5—C9—C8	161.4 (2)
C2—N2—C1—N3	1.3 (3)	N5—C5—C9—N4	174.8 (2)
C4—N3—C1—N1	177.94 (19)	C4—C5—C9—N4	−8.1 (3)
C4—N3—C1—N2	0.2 (3)	C9—C8—C10—C11	177.9 (2)
C1—N2—C2—C3	−1.5 (3)	C7—C8—C10—C11	4.9 (4)
N2—C2—C3—C4	0.4 (3)	C9—C8—C10—C15	−1.1 (2)
C1—N3—C4—C3	−1.5 (3)	C7—C8—C10—C15	−174.0 (2)
C1—N3—C4—C5	178.65 (18)	C15—C10—C11—C12	−1.1 (3)
C2—C3—C4—N3	1.3 (3)	C8—C10—C11—C12	−179.9 (2)
C2—C3—C4—C5	−178.92 (19)	C10—C11—C12—C13	−0.3 (3)
N3—C4—C5—N5	−154.0 (2)	C11—C12—C13—C14	1.2 (4)
C3—C4—C5—N5	26.2 (3)	C12—C13—C14—C15	−0.6 (3)
N3—C4—C5—C9	28.7 (3)	C9—N4—C15—C14	179.5 (2)
C3—C4—C5—C9	−151.1 (2)	C9—N4—C15—C10	−1.2 (2)
N5—C6—C7—C8	−44.9 (3)	C13—C14—C15—N4	178.4 (2)
C6—C7—C8—C9	25.0 (3)	C13—C14—C15—C10	−0.9 (3)
C6—C7—C8—C10	−162.7 (2)	C11—C10—C15—N4	−177.72 (19)
C10—C8—C9—N4	0.4 (3)	C8—C10—C15—N4	1.4 (2)
C7—C8—C9—N4	174.49 (18)	C11—C10—C15—C14	1.7 (3)
C10—C8—C9—C5	−170.84 (19)	C8—C10—C15—C14	−179.2 (2)
C7—C8—C9—C5	3.3 (3)	C9—C5—N5—C6	−5.1 (3)
C15—N4—C9—C8	0.5 (3)	C4—C5—N5—C6	177.67 (18)
C15—N4—C9—C5	171.0 (2)	C7—C6—N5—C5	36.6 (3)
N5—C5—C9—C8	−15.7 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	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+3/2, z−1/2; (ii) −x+1, y+1/2, −z+3/2.

Experimental details

Crystal data
Chemical formula	C₁₅H₁₃N₅
M_r	263.30
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	120
a, b, c (Å)	11.4758 (2), 12.6095 (2), 8.9241 (2)
β (°)	102.116 (1)
V (Å³)	1262.59 (4)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.45 × 0.35 × 0.15

Data collection
Diffractometer	Bruker SMART APEX diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	11840, 2905, 2485
R_int	0.026
(sin θ/λ)_max (Å⁻¹)	0.650

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.037, 0.102, 1.02
No. of reflections	2905
No. of parameters	193
No. of restraints	3
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	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···A	D—H	H···A	D···A	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+3/2, z−1/2; (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

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