Methyl 2-(1H-indole-3-carboxamido)­acetate

Hu, F.; Zheng, L.; Zeng, X.C.; Li, K.P.

doi:10.1107/S1600536811006660

organic compounds

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ISSN: 2056-9890

Volume 67| Part 3| March 2011| Page o742

doi:10.1107/S1600536811006660

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Methyl 2-(1H-indole-3-carboxamido)acetate

Fang Hu,^a Le Zheng,^a Xiang Chao Zeng ^a ^* and Kai Ping Li ^a

^aDepartment of Chemistry, Jinan University, Guangzhou, Guangdong 510632, People's Republic of China
^*Correspondence e-mail: xczeng@126.com

(Received 5 February 2011; accepted 22 February 2011; online 26 February 2011)

The title compound, C₁₂H₁₂N₂O₃, was synthesized by condensation of methyl aminoacetate with 3-trichloroacetylindole. In the crystal, intermolecular N—H⋯O hydrogen bonds link the molecules into chains parallel to the b axis. The chains are further connected into a three-dimensional network by N—H⋯O hydrogen bonds involving the indole N atom. In the molecule, the indole skeleton is nearly planar [maximum deviation = 0.012 (1) Å] and the mean plane of the amido group is twisted from the mean plane of indole ring by 17.2 (1)°.

Related literature

For the bioactivity of indole derivatives, see: Di Fabio et al. (2007 ); Sharma & Tepe (2004 ). For related structures, see: Huang et al. (2009 , 2010 ).

Experimental

Crystal data

C₁₂H₁₂N₂O₃
M_r = 232.24
Orthorhombic, P 2₁ 2₁ 2₁
a = 8.0024 (2) Å
b = 9.1279 (2) Å
c = 15.9767 (3) Å
V = 1167.02 (4) Å³
Z = 4
Cu Kα radiation
μ = 0.80 mm⁻¹
T = 150 K
0.49 × 0.17 × 0.12 mm

Data collection

Oxford Gemini S Ultra area-detector diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2010) $[Oxford Diffraction (2010). CrysAlis PRO. Oxford Diffraction Ltd, Yarnton, England.]$ T_min = 0.694, T_max = 0.910
2269 measured reflections
1642 independent reflections
1613 reflections with I > 2σ(I)
R_int = 0.016

Refinement

R[F² > 2σ(F²)] = 0.029
wR(F²) = 0.077
S = 1.05
1642 reflections
155 parameters
H-atom parameters constrained
Δρ_max = 0.13 e Å⁻³
Δρ_min = −0.14 e Å⁻³
Absolute structure: Flack (1983 ), 568 Friedel pairs
Flack parameter: −0.2 (3)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2⋯O1ⁱ	0.88	2.00	2.8566 (17)	164
N1—H1A⋯O2ⁱⁱ	0.88	2.15	2.9680 (18)	154
Symmetry codes: (i) $[-x+2, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (ii) $[-x+{\script{3\over 2}}, -y, z-{\script{1\over 2}}]$ .

Data collection: CrysAlis PRO (Oxford Diffraction, 2010 $[Oxford Diffraction (2010). CrysAlis PRO. Oxford Diffraction Ltd, Yarnton, England.]$ ); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811006660/rz2556sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536811006660/rz2556Isup2.hkl

checkCIF report

Comment top

Many indole derivatives show important bioactivities, such as metabotropic receptor antagonists (Di Fabio et al., 2007) and protein kinase inhibiting activity (Sharma & Tepe, 2004). This is the reason they have attracted our interest. This study is related to our previous structural investigations of methyl 3-(1-butyl-1H-indole-3-carbonyl)aminopropionate (Huang et al., 2009) and methyl 3-(1H-indole-3-carbonyl)aminopropionate hemihydrate (Huang et al., 2010).

The molecular structure of the title compound is shown in Fig. 1. In the crystal structure, molecules of the title compound are linked through N2—H2···O1 H-bonds (Table 1) to form chains extending along the b axis, which are further connected by N1—HA···O2 H-bonds to form the three-dimensional network (Fig. 2 and Fig. 3). Bond lengths and angles are unexceptional.

Related literature top

For the bioactivity of indole derivatives, see: Di Fabio et al. (2007); Sharma & Tepe (2004). For related structures, see: Huang et al. (2009, 2010).

Experimental top

The hydrochloric acid salt of methyl aminoacetate (0.63 g, 5 mmol) and 3-trichloroacetylindole (1.32 g, 5 mmol) were added to acetonitrile (10 ml), followed by the dropwise addition of triethylamine (1.2 ml). The mixture was stirred at room temperature for 12 h and then poured into water. After filtration, the precipitate was collected as a yellow solid. The impure product was dissolved in EtOH at room temperature, light yellow orthorhombic crystals suitable for X-ray analysis (m.p. 448 K, 89.2% yield) grew over a period of one week on slow evaporation of the solvent.

Computing details top

Data collection: CrysAlis PRO (Oxford Diffraction, 2010); cell refinement: CrysAlis PRO (Oxford Diffraction, 2010); data reduction: CrysAlis PRO (Oxford Diffraction, 2010); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

	Fig. 1. The molecular structure of the title compound, with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 2. Crystal packing of the title compound viewed approximately along the a axis. Dashed lines indicate hydrogen bonds.
	Fig. 3. Crystal packing of the title compound viewed along the b axis. Dashed lines indicate hydrogen bonds.

Methyl 2-(1H-indole-3-carboxamido)acetate top

Crystal data top

C₁₂H₁₂N₂O₃	D_x = 1.322 Mg m⁻³
M_r = 232.24	Melting point: 448 K
Orthorhombic, P2₁2₁2₁	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: P 2ac 2ab	Cell parameters from 1985 reflections
a = 8.0024 (2) Å	θ = 4.8–62.6°
b = 9.1279 (2) Å	µ = 0.80 mm⁻¹
c = 15.9767 (3) Å	T = 150 K
V = 1167.02 (4) Å³	Prism, light yellow
Z = 4	0.49 × 0.17 × 0.12 mm
F(000) = 488

Data collection top

Oxford Gemini S Ultra area-detector diffractometer	1642 independent reflections
Radiation source: fine-focus sealed tube	1613 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.016
ϕ and ω scans	θ_max = 62.7°, θ_min = 5.6°
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2010)	h = −5→9
T_min = 0.694, T_max = 0.910	k = −10→8
2269 measured reflections	l = −18→15

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.029	H-atom parameters constrained
wR(F²) = 0.077	w = 1/[σ²(F_o²) + (0.0478P)² + 0.0803P] where P = (F_o² + 2F_c²)/3
S = 1.05	(Δ/σ)_max = 0.011
1642 reflections	Δρ_max = 0.13 e Å⁻³
155 parameters	Δρ_min = −0.14 e Å⁻³
0 restraints	Absolute structure: Flack (1983), 568 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.2 (3)

Crystal data top

C₁₂H₁₂N₂O₃	V = 1167.02 (4) Å³
M_r = 232.24	Z = 4
Orthorhombic, P2₁2₁2₁	Cu Kα radiation
a = 8.0024 (2) Å	µ = 0.80 mm⁻¹
b = 9.1279 (2) Å	T = 150 K
c = 15.9767 (3) Å	0.49 × 0.17 × 0.12 mm

Data collection top

Oxford Gemini S Ultra area-detector diffractometer	1642 independent reflections
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2010)	1613 reflections with I > 2σ(I)
T_min = 0.694, T_max = 0.910	R_int = 0.016
2269 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.029	H-atom parameters constrained
wR(F²) = 0.077	Δρ_max = 0.13 e Å⁻³
S = 1.05	Δρ_min = −0.14 e Å⁻³
1642 reflections	Absolute structure: Flack (1983), 568 Friedel pairs
155 parameters	Absolute structure parameter: −0.2 (3)
0 restraints

Special details top

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

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

	x	y	z	U_iso*/U_eq
C1	0.8259 (2)	0.08538 (18)	0.12627 (10)	0.0418 (4)
H1	0.9222	0.0261	0.1184	0.050*
N1	0.68538 (19)	0.07824 (16)	0.07961 (9)	0.0491 (4)
H1A	0.6691	0.0180	0.0374	0.059*
C8	0.5711 (2)	0.17992 (19)	0.10821 (10)	0.0451 (4)
C3	0.6450 (2)	0.25391 (16)	0.17586 (9)	0.0400 (4)
C4	0.5524 (2)	0.36258 (18)	0.21720 (11)	0.0498 (4)
H4	0.5985	0.4145	0.2633	0.060*
C5	0.3925 (3)	0.3921 (2)	0.18931 (12)	0.0608 (5)
H5	0.3288	0.4657	0.2167	0.073*
C6	0.3219 (3)	0.3166 (3)	0.12172 (14)	0.0660 (6)
H6	0.2115	0.3397	0.1044	0.079*
C7	0.4094 (3)	0.2099 (2)	0.08007 (12)	0.0593 (5)
H7	0.3621	0.1586	0.0341	0.071*
C9	0.9272 (2)	0.22893 (16)	0.25277 (10)	0.0383 (4)
C10	1.1689 (2)	0.1685 (2)	0.33471 (10)	0.0432 (4)
H10A	1.2129	0.2687	0.3260	0.052*
H10B	1.2642	0.0995	0.3315	0.052*
C11	1.0915 (2)	0.15897 (18)	0.42041 (10)	0.0394 (4)
C12	1.1129 (3)	0.2444 (3)	0.55958 (11)	0.0767 (7)
H12A	1.1425	0.1492	0.5839	0.115*
H12B	0.9915	0.2577	0.5621	0.115*
H12C	1.1680	0.3226	0.5912	0.115*
C2	0.8088 (2)	0.19136 (16)	0.18683 (10)	0.0380 (4)
N2	1.05189 (17)	0.13476 (14)	0.26902 (8)	0.0419 (3)
H2	1.0620	0.0534	0.2399	0.050*
O1	0.91340 (16)	0.34378 (12)	0.29446 (7)	0.0476 (3)
O2	0.97901 (16)	0.07845 (14)	0.43919 (8)	0.0561 (4)
O3	1.16709 (15)	0.24943 (15)	0.47336 (7)	0.0549 (4)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0480 (9)	0.0397 (8)	0.0377 (8)	0.0024 (8)	−0.0025 (8)	−0.0015 (7)
N1	0.0594 (9)	0.0479 (8)	0.0401 (7)	0.0050 (8)	−0.0094 (7)	−0.0091 (7)
C8	0.0508 (10)	0.0442 (9)	0.0404 (9)	0.0019 (8)	−0.0013 (8)	0.0033 (8)
C3	0.0511 (9)	0.0351 (8)	0.0339 (7)	0.0003 (7)	0.0034 (8)	0.0053 (7)
C4	0.0644 (11)	0.0433 (8)	0.0417 (9)	0.0059 (9)	0.0127 (9)	0.0024 (8)
C5	0.0680 (12)	0.0583 (11)	0.0561 (11)	0.0205 (10)	0.0158 (11)	0.0109 (9)
C6	0.0540 (11)	0.0778 (14)	0.0662 (13)	0.0175 (11)	0.0044 (11)	0.0201 (12)
C7	0.0564 (11)	0.0669 (12)	0.0546 (11)	0.0039 (11)	−0.0117 (10)	0.0074 (10)
C9	0.0491 (9)	0.0338 (7)	0.0319 (7)	−0.0079 (7)	0.0056 (7)	0.0023 (7)
C10	0.0386 (8)	0.0511 (9)	0.0398 (8)	−0.0043 (8)	0.0017 (8)	−0.0026 (8)
C11	0.0371 (8)	0.0409 (8)	0.0403 (9)	−0.0010 (8)	−0.0037 (7)	0.0024 (7)
C12	0.0694 (13)	0.1237 (19)	0.0370 (9)	−0.0244 (14)	0.0026 (10)	−0.0143 (12)
C2	0.0483 (9)	0.0319 (8)	0.0337 (8)	−0.0024 (7)	0.0030 (7)	0.0011 (6)
N2	0.0491 (8)	0.0394 (6)	0.0372 (7)	−0.0002 (6)	0.0000 (6)	−0.0061 (6)
O1	0.0636 (7)	0.0346 (5)	0.0446 (6)	−0.0035 (6)	−0.0024 (6)	−0.0080 (5)
O2	0.0574 (7)	0.0629 (7)	0.0481 (7)	−0.0217 (7)	0.0045 (6)	0.0062 (6)
O3	0.0528 (7)	0.0742 (8)	0.0376 (6)	−0.0197 (7)	−0.0002 (6)	−0.0072 (7)

Geometric parameters (Å, º) top

C1—N1	1.351 (2)	C7—H7	0.9500
C1—C2	1.375 (2)	C9—O1	1.2470 (19)
C1—H1	0.9500	C9—N2	1.342 (2)
N1—C8	1.381 (2)	C9—C2	1.458 (2)
N1—H1A	0.8800	C10—N2	1.440 (2)
C8—C7	1.397 (3)	C10—C11	1.505 (2)
C8—C3	1.405 (2)	C10—H10A	0.9900
C3—C4	1.403 (2)	C10—H10B	0.9900
C3—C2	1.440 (2)	C11—O2	1.2002 (19)
C4—C5	1.381 (3)	C11—O3	1.328 (2)
C4—H4	0.9500	C12—O3	1.445 (2)
C5—C6	1.400 (3)	C12—H12A	0.9800
C5—H5	0.9500	C12—H12B	0.9800
C6—C7	1.372 (3)	C12—H12C	0.9800
C6—H6	0.9500	N2—H2	0.8800

N1—C1—C2	109.84 (15)	O1—C9—C2	121.73 (15)
N1—C1—H1	125.1	N2—C9—C2	118.18 (13)
C2—C1—H1	125.1	N2—C10—C11	112.53 (13)
C1—N1—C8	109.64 (14)	N2—C10—H10A	109.1
C1—N1—H1A	125.2	C11—C10—H10A	109.1
C8—N1—H1A	125.2	N2—C10—H10B	109.1
N1—C8—C7	129.68 (17)	C11—C10—H10B	109.1
N1—C8—C3	107.41 (15)	H10A—C10—H10B	107.8
C7—C8—C3	122.90 (17)	O2—C11—O3	124.28 (16)
C4—C3—C8	118.67 (16)	O2—C11—C10	124.84 (15)
C4—C3—C2	134.70 (16)	O3—C11—C10	110.86 (14)
C8—C3—C2	106.61 (14)	O3—C12—H12A	109.5
C5—C4—C3	118.38 (18)	O3—C12—H12B	109.5
C5—C4—H4	120.8	H12A—C12—H12B	109.5
C3—C4—H4	120.8	O3—C12—H12C	109.5
C4—C5—C6	121.75 (18)	H12A—C12—H12C	109.5
C4—C5—H5	119.1	H12B—C12—H12C	109.5
C6—C5—H5	119.1	C1—C2—C3	106.50 (14)
C7—C6—C5	121.2 (2)	C1—C2—C9	127.52 (15)
C7—C6—H6	119.4	C3—C2—C9	125.89 (14)
C5—C6—H6	119.4	C9—N2—C10	119.16 (13)
C6—C7—C8	117.10 (19)	C9—N2—H2	120.4
C6—C7—H7	121.4	C10—N2—H2	120.4
C8—C7—H7	121.4	C11—O3—C12	116.79 (14)
O1—C9—N2	120.08 (15)

C2—C1—N1—C8	0.05 (19)	N1—C1—C2—C3	−0.22 (18)
C1—N1—C8—C7	−178.97 (19)	N1—C1—C2—C9	176.50 (15)
C1—N1—C8—C3	0.15 (19)	C4—C3—C2—C1	178.82 (17)
N1—C8—C3—C4	−179.08 (14)	C8—C3—C2—C1	0.30 (17)
C7—C8—C3—C4	0.1 (3)	C4—C3—C2—C9	2.0 (3)
N1—C8—C3—C2	−0.28 (18)	C8—C3—C2—C9	−176.48 (14)
C7—C8—C3—C2	178.92 (16)	O1—C9—C2—C1	166.46 (15)
C8—C3—C4—C5	−0.1 (2)	N2—C9—C2—C1	−14.7 (2)
C2—C3—C4—C5	−178.51 (18)	O1—C9—C2—C3	−17.4 (2)
C3—C4—C5—C6	0.2 (3)	N2—C9—C2—C3	161.42 (15)
C4—C5—C6—C7	−0.2 (3)	O1—C9—N2—C10	−0.2 (2)
C5—C6—C7—C8	0.2 (3)	C2—C9—N2—C10	−179.07 (14)
N1—C8—C7—C6	178.87 (18)	C11—C10—N2—C9	69.72 (19)
C3—C8—C7—C6	−0.1 (3)	O2—C11—O3—C12	2.6 (3)
N2—C10—C11—O2	30.2 (2)	C10—C11—O3—C12	−175.89 (17)
N2—C10—C11—O3	−151.31 (14)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O1ⁱ	0.88	2.00	2.8566 (17)	164
N1—H1A···O2ⁱⁱ	0.88	2.15	2.9680 (18)	154

Symmetry codes: (i) −x+2, y−1/2, −z+1/2; (ii) −x+3/2, −y, z−1/2.

Experimental details

Crystal data
Chemical formula	C₁₂H₁₂N₂O₃
M_r	232.24
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	150
a, b, c (Å)	8.0024 (2), 9.1279 (2), 15.9767 (3)
V (Å³)	1167.02 (4)
Z	4
Radiation type	Cu Kα
µ (mm⁻¹)	0.80
Crystal size (mm)	0.49 × 0.17 × 0.12

Data collection
Diffractometer	Oxford Gemini S Ultra area-detector diffractometer
Absorption correction	Multi-scan (CrysAlis PRO; Oxford Diffraction, 2010)
T_min, T_max	0.694, 0.910
No. of measured, independent and observed [I > 2σ(I)] reflections	2269, 1642, 1613
R_int	0.016
(sin θ/λ)_max (Å⁻¹)	0.576

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.029, 0.077, 1.05
No. of reflections	1642
No. of parameters	155
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.13, −0.14
Absolute structure	Flack (1983), 568 Friedel pairs
Absolute structure parameter	−0.2 (3)

Computer programs: CrysAlis PRO (Oxford Diffraction, 2010), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O1ⁱ	0.88	2.00	2.8566 (17)	164
N1—H1A···O2ⁱⁱ	0.88	2.15	2.9680 (18)	154

Symmetry codes: (i) −x+2, y−1/2, −z+1/2; (ii) −x+3/2, −y, z−1/2.

Acknowledgements

We thank the Natural Science Foundation of Guangdong Province, China (No. 06300581) for generously supporting this study.

References

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