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Acta Cryst. (2007). E63, o3389    [ doi:10.1107/S1600536807031285 ]

5-Chloro-3-ethyl-N-[2-(morpholin-4-yl)ethyl]-1H-indole-2-carboxamide

K. E. A. Muirhead, L. Trembleau and W. T. A. Harrison

Abstract top

In the title compound, C17H22ClN3O2, the aromatic fused ring system and the amide group are close to being coplanar [dihedral angle = 14.66 (16)°]. Thus, the amide NH group is sterically blocked from forming a hydrogen bond by the pendant ethyl substituent of the adjacent five-membered ring. The NH group of the five-membered ring makes an intermolecular N-H...O bond, resulting in centrosymmetric dimers of molecules containing R22(10) loops.

Comment top

As part of our on-going investigations of allosteric modulators of the cannabinoid CB1 receptor (Price et al., 2005), the title compound, (I), C17H22ClN3O2, has been synthesized and structurally characterized (Fig. 1). It complements C18H24ClN3O2, reported in the next paper (Muirhead, Trembleau & Harrison, 2007).

The dihedral angle between the mean planes of the C1—C8/N1 fused aromatic ring system and atoms C6/C7/N1/O2 in (I) is 14.66 (16)°, i.e. the two fragments are slightly twisted. Atom C10 is displaced from the C1—C8/N1 mean plane by 1.459 (14) Å. The C14—C17/N3/O2 ring in (I) has a typical chair conformation, with N3 and O2 displaced from the mean plane of the carbon atoms by −0.656 (12)Å and 0.635 (14) Å, respectively. Otherwise, the bond lengths and angles in (I) may be regarded as normal (Allen et al., 1995).

The crystal packing for (I) results in inversion dimers linked by N1—H1···O1i hydrogen bonds (Table 1), thus forming R22(10) loops (Bernstein et al., 1995). The amide N2—H2 group is sterically blocked by the C9/C10 ethyl substituent to the 5-membered ring from making an hydrogen bond. A short C—H···O interaction also occurs (Table 1).

Related literature top

For a related structure, see: Muirhead et al. (2007). For background, see: Price et al. (2005); Allen et al. (1995); Bernstein et al. (1995). For related literature, see: Muirhead & Trembleau (2007).

Experimental top

To a solution of pentafluorophenol (0.130 g, 0.706 mmol) in dichloromethane (5 ml), 3-ethylindole-2-carboxylic acid (0.100 g, 0.447 mmol) (Muirhead & Trembleau, 2007) and N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.111 g, 0.581 mmol) were added and stirred at room temperature for 80 min. Silica gel (1.2 g) was added to the reaction mixture, stirred for 5 min and the mixture filtered through Celite and the solvent removed to give the activated ester as a white solid (0.167 g). The ester was redissolved in dichloromethane (2.6 ml), to which was added 2-morpholinoethylamine 5 (0.068 ml, 0.514 mmol) and triethylamine (0.072 ml, 0.514 mmol) and stirred at room temperature for 80 min. The solvent was removed under vacuum and the resulting solid taken up into ethyl acetate (30 ml), washed with saturated potassium carbonate solution (5 ml), dried over magnesium sulfate, filtered and dried. Recrystallization of the crude material from hot ethanol afforded 0.066 g (44%) of colourless blocks of (I)

Refinement top

The H atoms were placed in idealized locations (C—H = 0.93–0.99 Å, N—H = 0.88 Å) and refined as riding with Uiso(H) = 1.2Ueq(C,N) or 1.5Ueq(methyl C).

Computing details top

Data collection: COLLECT (Nonius, 1998); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: SCALEPACK and DENZO (Otwinowski & Minor, 1997), and SORTAV (Blessing, 1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXL97.

Figures top
[Figure 1] Fig. 1. View of the molecular structure of (I) showing 40% displacement ellipsoids.
[Figure 2] Fig. 2. An inversion dimer in the crystal of (I) with hydrogen bonds shown as double dashed lines. All carbon-bound H atoms are omitted for clarity. Symmetry code as in Table 1.
5-Chloro-3-ethyl-N-(2-morpholin-4-ylethyl)-1H-indole-2-carboxamide top
Crystal data top
C17H22ClN3O2Z = 2
Mr = 335.83F(000) = 356
Triclinic, P1Dx = 1.296 Mg m−3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 9.1886 (13) ÅCell parameters from 3029 reflections
b = 9.7175 (13) Åθ = 2.9–27.5°
c = 11.2807 (10) ŵ = 0.24 mm−1
α = 73.755 (6)°T = 120 K
β = 79.612 (6)°Block, colourles
γ = 63.056 (5)°0.12 × 0.08 × 0.06 mm
V = 860.38 (18) Å3
Data collection top
Nonius KappaCCD
diffractometer		3155 independent reflections
Radiation source: fine-focus sealed tube1516 reflections with I > 2σ(I)
graphiteRint = 0.159
ω and φ scansθmax = 25.5°, θmin = 3.0°
Absorption correction: multi-scan
(SADABS; Bruker, 2003)		h = −11→11
Tmin = 0.972, Tmax = 0.987k = −11→11
10924 measured reflectionsl = −13→13
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)] = 0.129Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.289H-atom parameters constrained
S = 1.07 w = 1/[σ2(Fo2) + (0.039P)2 + 4.7894P]
where P = (Fo2 + 2Fc2)/3
3155 reflections(Δ/σ)max < 0.001
208 parametersΔρmax = 0.36 e Å−3
0 restraintsΔρmin = −0.38 e Å−3
Crystal data top
C17H22ClN3O2γ = 63.056 (5)°
Mr = 335.83V = 860.38 (18) Å3
Triclinic, P1Z = 2
a = 9.1886 (13) ÅMo Kα radiation
b = 9.7175 (13) ŵ = 0.24 mm−1
c = 11.2807 (10) ÅT = 120 K
α = 73.755 (6)°0.12 × 0.08 × 0.06 mm
β = 79.612 (6)°
Data collection top
Nonius KappaCCD
diffractometer		3155 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2003)		1516 reflections with I > 2σ(I)
Tmin = 0.972, Tmax = 0.987Rint = 0.159
10924 measured reflectionsθmax = 25.5°
Refinement top
R[F2 > 2σ(F2)] = 0.129H-atom parameters constrained
wR(F2) = 0.289Δρmax = 0.36 e Å−3
S = 1.07Δρmin = −0.38 e Å−3
3155 reflectionsAbsolute structure: ?
208 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
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
xyzUiso*/Ueq
C10.9563 (9)0.2441 (9)0.5535 (6)0.0404 (19)
C21.0584 (10)0.1514 (9)0.4714 (7)0.046 (2)
H2A1.12220.04140.50160.055*
C31.0679 (9)0.2169 (9)0.3478 (7)0.0393 (18)
H31.13650.15470.29080.047*
C40.9723 (9)0.3796 (8)0.3089 (6)0.0353 (18)
C50.8706 (9)0.4732 (9)0.3911 (7)0.0356 (17)
C60.8631 (9)0.4013 (9)0.5165 (6)0.0399 (19)
H60.79410.46160.57460.048*
C70.8504 (9)0.6271 (8)0.1992 (6)0.0364 (18)
C80.7926 (9)0.6324 (8)0.3215 (6)0.0368 (18)
C90.6664 (10)0.7674 (9)0.3750 (7)0.050 (2)
H9A0.68600.86300.33710.060*
H9B0.67930.74170.46490.060*
C100.4926 (12)0.8046 (14)0.3552 (10)0.089 (4)
H10A0.41630.89330.39250.134*
H10B0.47130.71130.39390.134*
H10C0.47770.83340.26630.134*
C110.8181 (9)0.7478 (9)0.0822 (7)0.0399 (19)
C120.7132 (13)1.0292 (9)−0.0191 (7)0.061 (3)
H12A0.59911.0711−0.04170.073*
H12B0.78750.9927−0.09030.073*
C130.7398 (12)1.1575 (10)0.0105 (7)0.057 (2)
H13A0.85841.12290.01430.069*
H13B0.69931.2542−0.05650.069*
C140.4797 (11)1.2850 (12)0.1173 (8)0.063 (3)
H14A0.43561.22230.09200.075*
H14B0.45691.38430.05300.075*
C150.3973 (12)1.3236 (14)0.2387 (10)0.086 (4)
H15A0.27851.38750.22890.103*
H15B0.41211.22380.30040.103*
C160.6288 (13)1.3189 (14)0.2949 (10)0.080 (3)
H16A0.65011.21820.35710.096*
H16B0.67211.37930.32430.096*
C170.7163 (10)1.2833 (11)0.1741 (8)0.060 (2)
H17A0.70021.38380.11290.072*
H17B0.83501.22110.18510.072*
N10.9593 (7)0.4741 (7)0.1933 (5)0.0373 (15)
H11.01190.44270.12560.045*
N20.7448 (9)0.8985 (7)0.0874 (5)0.053 (2)
H20.71300.92070.16090.064*
N30.6561 (8)1.1948 (7)0.1276 (6)0.0426 (16)
O10.8611 (7)0.7085 (6)−0.0193 (5)0.0570 (16)
O20.4578 (8)1.4077 (9)0.2841 (7)0.086 (2)
Cl10.9493 (3)0.1505 (3)0.71052 (19)0.0626 (7)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.038 (5)0.045 (5)0.034 (4)−0.022 (4)−0.005 (4)0.005 (4)
C20.039 (5)0.039 (5)0.047 (5)−0.008 (4)−0.003 (4)−0.006 (4)
C30.034 (4)0.042 (5)0.039 (4)−0.014 (4)0.001 (3)−0.013 (4)
C40.031 (4)0.036 (4)0.041 (4)−0.018 (4)0.003 (3)−0.009 (4)
C50.031 (4)0.038 (4)0.043 (4)−0.017 (4)0.000 (4)−0.015 (4)
C60.041 (5)0.046 (5)0.031 (4)−0.020 (4)0.008 (3)−0.011 (4)
C70.040 (5)0.033 (4)0.035 (4)−0.014 (4)−0.004 (3)−0.007 (3)
C80.037 (4)0.035 (4)0.040 (4)−0.014 (4)0.004 (4)−0.017 (4)
C90.061 (6)0.044 (5)0.037 (4)−0.019 (4)0.002 (4)−0.008 (4)
C100.052 (7)0.104 (9)0.083 (8)−0.007 (6)0.008 (6)−0.033 (7)
C110.042 (5)0.037 (5)0.039 (4)−0.014 (4)−0.003 (4)−0.010 (4)
C120.103 (8)0.037 (5)0.034 (4)−0.025 (5)−0.003 (5)−0.003 (4)
C130.072 (7)0.042 (5)0.047 (5)−0.019 (5)0.008 (5)−0.008 (4)
C140.063 (7)0.074 (7)0.063 (6)−0.040 (6)−0.001 (5)−0.017 (5)
C150.047 (6)0.115 (9)0.112 (9)−0.034 (6)0.018 (6)−0.066 (8)
C160.070 (8)0.105 (9)0.099 (8)−0.044 (7)0.005 (6)−0.069 (7)
C170.040 (5)0.059 (6)0.077 (6)−0.012 (5)−0.001 (5)−0.029 (5)
N10.044 (4)0.035 (4)0.029 (3)−0.012 (3)0.003 (3)−0.014 (3)
N20.089 (6)0.032 (4)0.026 (3)−0.015 (4)0.000 (3)−0.009 (3)
N30.038 (4)0.045 (4)0.048 (4)−0.015 (3)0.000 (3)−0.021 (3)
O10.071 (4)0.048 (3)0.035 (3)−0.008 (3)−0.001 (3)−0.018 (3)
O20.049 (4)0.105 (6)0.129 (6)−0.031 (4)0.018 (4)−0.080 (5)
Cl10.0756 (17)0.0625 (15)0.0402 (12)−0.0305 (13)−0.0032 (11)0.0040 (10)
Geometric parameters (Å, °) top
C1—C61.352 (10)C12—N21.442 (9)
C1—C21.393 (10)C12—C131.505 (11)
C1—Cl11.754 (7)C12—H12A0.9900
C2—C31.366 (10)C12—H12B0.9900
C2—H2A0.9500C13—N31.455 (9)
C3—C41.399 (10)C13—H13A0.9900
C3—H30.9500C13—H13B0.9900
C4—N11.357 (9)C14—N31.460 (11)
C4—C51.397 (9)C14—C151.499 (12)
C5—C61.397 (10)C14—H14A0.9900
C5—C81.429 (10)C14—H14B0.9900
C6—H60.9500C15—O21.410 (11)
C7—N11.378 (9)C15—H15A0.9900
C7—C81.393 (9)C15—H15B0.9900
C7—C111.472 (10)C16—O21.418 (11)
C8—C91.497 (10)C16—C171.497 (12)
C9—C101.514 (12)C16—H16A0.9900
C9—H9A0.9900C16—H16B0.9900
C9—H9B0.9900C17—N31.452 (10)
C10—H10A0.9800C17—H17A0.9900
C10—H10B0.9800C17—H17B0.9900
C10—H10C0.9800N1—H10.8800
C11—O11.248 (8)N2—H20.8800
C11—N21.319 (9)
C6—C1—C2122.5 (7)C13—C12—H12B109.8
C6—C1—Cl1119.6 (6)H12A—C12—H12B108.3
C2—C1—Cl1117.9 (6)N3—C13—C12111.9 (7)
C3—C2—C1120.7 (7)N3—C13—H13A109.2
C3—C2—H2A119.7C12—C13—H13A109.2
C1—C2—H2A119.7N3—C13—H13B109.2
C2—C3—C4117.1 (7)C12—C13—H13B109.2
C2—C3—H3121.4H13A—C13—H13B107.9
C4—C3—H3121.4N3—C14—C15110.3 (8)
N1—C4—C5108.2 (6)N3—C14—H14A109.6
N1—C4—C3129.4 (7)C15—C14—H14A109.6
C5—C4—C3122.3 (7)N3—C14—H14B109.6
C4—C5—C6118.7 (7)C15—C14—H14B109.6
C4—C5—C8107.9 (6)H14A—C14—H14B108.1
C6—C5—C8133.4 (7)O2—C15—C14113.3 (8)
C1—C6—C5118.6 (7)O2—C15—H15A108.9
C1—C6—H6120.7C14—C15—H15A108.9
C5—C6—H6120.7O2—C15—H15B108.9
N1—C7—C8109.4 (6)C14—C15—H15B108.9
N1—C7—C11117.3 (6)H15A—C15—H15B107.7
C8—C7—C11133.3 (7)O2—C16—C17111.7 (8)
C7—C8—C5105.4 (6)O2—C16—H16A109.3
C7—C8—C9130.1 (7)C17—C16—H16A109.3
C5—C8—C9124.3 (6)O2—C16—H16B109.3
C8—C9—C10113.5 (7)C17—C16—H16B109.3
C8—C9—H9A108.9H16A—C16—H16B107.9
C10—C9—H9A108.9N3—C17—C16111.0 (7)
C8—C9—H9B108.9N3—C17—H17A109.4
C10—C9—H9B108.9C16—C17—H17A109.4
H9A—C9—H9B107.7N3—C17—H17B109.4
C9—C10—H10A109.5C16—C17—H17B109.4
C9—C10—H10B109.5H17A—C17—H17B108.0
H10A—C10—H10B109.5C4—N1—C7109.1 (6)
C9—C10—H10C109.5C4—N1—H1125.5
H10A—C10—H10C109.5C7—N1—H1125.5
H10B—C10—H10C109.5C11—N2—C12124.4 (6)
O1—C11—N2120.9 (7)C11—N2—H2117.8
O1—C11—C7120.8 (7)C12—N2—H2117.8
N2—C11—C7118.3 (6)C17—N3—C13112.2 (6)
N2—C12—C13109.3 (7)C17—N3—C14108.7 (6)
N2—C12—H12A109.8C13—N3—C14111.6 (7)
C13—C12—H12A109.8C15—O2—C16109.2 (7)
N2—C12—H12B109.8
C6—C1—C2—C3−0.3 (12)N1—C7—C11—O114.0 (11)
Cl1—C1—C2—C3179.3 (6)C8—C7—C11—O1−166.0 (8)
C1—C2—C3—C40.5 (11)N1—C7—C11—N2−165.1 (7)
C2—C3—C4—N1179.5 (7)C8—C7—C11—N214.9 (13)
C2—C3—C4—C5−0.1 (11)N2—C12—C13—N3−48.9 (10)
N1—C4—C5—C6179.8 (6)N3—C14—C15—O256.9 (12)
C3—C4—C5—C6−0.6 (11)O2—C16—C17—N3−58.9 (11)
N1—C4—C5—C8−0.2 (8)C5—C4—N1—C7−0.3 (8)
C3—C4—C5—C8179.4 (7)C3—C4—N1—C7−179.8 (7)
C2—C1—C6—C5−0.3 (12)C8—C7—N1—C40.6 (8)
Cl1—C1—C6—C5−179.9 (6)C11—C7—N1—C4−179.4 (6)
C4—C5—C6—C10.8 (11)O1—C11—N2—C12−2.5 (13)
C8—C5—C6—C1−179.2 (8)C7—C11—N2—C12176.6 (8)
N1—C7—C8—C5−0.7 (8)C13—C12—N2—C11−141.5 (8)
C11—C7—C8—C5179.3 (8)C16—C17—N3—C13−179.6 (8)
N1—C7—C8—C9−176.1 (7)C16—C17—N3—C1456.5 (10)
C11—C7—C8—C93.9 (14)C12—C13—N3—C17163.8 (7)
C4—C5—C8—C70.6 (8)C12—C13—N3—C14−74.0 (9)
C6—C5—C8—C7−179.5 (8)C15—C14—N3—C17−54.9 (10)
C4—C5—C8—C9176.3 (7)C15—C14—N3—C13−179.1 (7)
C6—C5—C8—C9−3.7 (13)C14—C15—O2—C16−56.9 (12)
C7—C8—C9—C1076.4 (11)C17—C16—O2—C1557.2 (11)
C5—C8—C9—C10−98.2 (9)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.881.972.803 (7)157
C6—H6···O2ii0.952.583.491 (11)161
Symmetry codes: (i) −x+2, −y+1, −z; (ii) −x+1, −y+2, −z+1.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.881.972.803 (7)157
C6—H6···O2ii0.952.583.491 (11)161
Symmetry codes: (i) −x+2, −y+1, −z; (ii) −x+1, −y+2, −z+1.
Acknowledgements top

We thank the EPSRC UK National Crystallography Service (University of Southampton) for the data collection.

references
References top

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