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

Journal logoIUCrDATA
ISSN: 2414-3146

Ethyl 3-[3-amino-4-methyl­amino-N-(pyridin-2-yl)benzamido]­propano­ate

aCollege of Chemistry and Chemical Engineering, Southeast University, Nanjing 210096, People's Republic of China
*Correspondence e-mail: wgjzt@sina.com

Edited by D.-J. Xu, Zhejiang University (Yuquan Campus), China (Received 25 September 2016; accepted 4 December 2016; online 3 February 2017)

In the title compound, C18H22N4O3, the benzene ring is twisted by 63.29 (15)° with respect to the pyridine ring. In the crystal, mol­ecules are linked by N—H⋯O hydrogen bonds and C—H⋯π inter­actions, forming slabs parallel to the ac plane.

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

Structure description

The title compound (Fig. 1[link]), an important inter­mediate of dabigatran etexilate, has attracted much attention due to its oral anti­coagulant properties (Chen et al., 2013[Chen, Y., Liang, J., Chen, H.-S. & Yuan, L. (2013). Heterocycles, 87, 1699-1710.]).

[Figure 1]
Figure 1
The mol­ecular structure of the title compound, showing the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

The benzene ring forms a dihedral angles of 63.29 (15)° with the pyridine ring. The mean plane through the C15/C14/N3 fragment makes dihedral angles of 83.5 (3) and 56.0 (3)° with the pyridine and benzene rings, respectively. The N2—C5 bond [1.386 (3) Å] is slightly shorter than the N1—C4 bond [1.412 (4) Å], which implies that the –NH–CH3 group is a stronger electron-donating group compared to the NH2 group, thus resulting in a slightly shorter bond length.

In the crystal, mol­ecules are linked by N—H⋯O hydrogen bonds (Table 1[link]). The N1—H1B⋯O2ii hydrogen bond leads to the formation of chains along [101], while the N1—H1A⋯O1i hydrogen bond and C—H⋯π inter­action link the mol­ecules to form slabs parallel to the ac plane (Table 1[link] and Fig. 2[link]).

Table 1
Hydrogen-bond geometry (Å, °)

Cg2 is the centroid of the C2–C7 benzene ring.

D—H⋯A D—H H⋯A DA D—H⋯A
N1—H1A⋯O1i 0.86 2.31 3.035 (3) 142
N1—H1B⋯O2ii 0.86 2.41 3.018 (4) 128
C12—H12ACg2iii 0.93 2.79 3.566 (4) 142
Symmetry codes: (i) -x, -y, -z+1; (ii) x-1, y, z-1; (iii) x+1, y, z.
[Figure 2]
Figure 2
A view along the c axis of the crystal packing, with hydrogen bonds shown as dashed lines (see Table 1[link]).

Synthesis and crystallization

The title compound was synthesized by the procedures reported by Chen et al. (2013[Chen, Y., Liang, J., Chen, H.-S. & Yuan, L. (2013). Heterocycles, 87, 1699-1710.]). Single crystals were obtained from methanol solution.

Refinement

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

Table 2
Experimental details

Crystal data
Chemical formula C18H22N4O3
Mr 342.39
Crystal system, space group Triclinic, P[\overline{1}]
Temperature (K) 293
a, b, c (Å) 8.3380 (17), 10.435 (2), 10.885 (2)
α, β, γ (°) 102.95 (3), 97.94 (3), 97.51 (3)
V3) 901.2 (3)
Z 2
Radiation type Mo Kα
μ (mm−1) 0.09
Crystal size (mm) 0.20 × 0.10 × 0.10
 
Data collection
Diffractometer Enraf–Nonius CAD-4
No. of measured, independent and observed [I > 2σ(I)] reflections 3550, 3305, 1996
Rint 0.025
(sin θ/λ)max−1) 0.603
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.063, 0.192, 1.01
No. of reflections 3305
No. of parameters 226
No. of restraints 1
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.35, −0.25
Computer programs: CrystalClear (Rigaku, 2005[Rigaku. (2005). CrystalClear. Rigaku Corporation, Tokyo, Japan.]), SHELXS97 and SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]) and ORTEP-3 for Windows (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]).

Structural data


Computing details top

Data collection: CrystalClear (Rigaku, 2005); cell refinement: CrystalClear (Rigaku, 2005); data reduction: CrystalClear (Rigaku, 2005); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Ethyl 3-[3-amino-4-methylamino-N-(pyridin-2-yl)benzamido]propanoate top
Crystal data top
C18H22N4O3Z = 2
Mr = 342.39F(000) = 364
Triclinic, P1Dx = 1.262 Mg m3
a = 8.3380 (17) ÅMo Kα radiation, λ = 0.71073 Å
b = 10.435 (2) ÅCell parameters from 445 reflections
c = 10.885 (2) Åθ = 2.4–22.8°
α = 102.95 (3)°µ = 0.09 mm1
β = 97.94 (3)°T = 293 K
γ = 97.51 (3)°Block, brown
V = 901.2 (3) Å30.20 × 0.10 × 0.10 mm
Data collection top
Enraf–Nonius CAD-4
diffractometer
θmax = 25.4°, θmin = 2.0°
Radiation source: fine-focus sealed tubeh = 010
ω/2θ scansk = 1212
3550 measured reflectionsl = 1312
3305 independent reflections3 standard reflections every 200 reflections
1996 reflections with I > 2σ(I) intensity decay: 1%
Rint = 0.025
Refinement top
Refinement on F21 restraint
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.063H-atom parameters constrained
wR(F2) = 0.192 w = 1/[σ2(Fo2) + (0.1P)2]
where P = (Fo2 + 2Fc2)/3
S = 1.01(Δ/σ)max < 0.001
3305 reflectionsΔρmax = 0.35 e Å3
226 parametersΔρmin = 0.25 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.2166 (3)0.1355 (2)0.65272 (19)0.0547 (6)
N10.0262 (3)0.0047 (2)0.1767 (2)0.0445 (6)
H1A0.06240.07310.20280.053*
H1B0.06350.00120.10080.053*
C10.3201 (3)0.1803 (3)0.5971 (3)0.0385 (7)
N20.0901 (3)0.2199 (3)0.0943 (2)0.0515 (7)
H2A0.00840.16150.04970.062*
C20.2749 (3)0.1894 (3)0.4627 (3)0.0353 (7)
O20.6824 (3)0.0688 (3)1.0268 (3)0.0793 (8)
N30.4777 (3)0.2287 (2)0.6610 (2)0.0399 (6)
C30.1552 (3)0.0899 (3)0.3803 (3)0.0356 (7)
H3A0.11540.01600.40840.043*
O30.6338 (4)0.2761 (3)1.0443 (2)0.0796 (9)
C40.0943 (3)0.0979 (3)0.2585 (3)0.0354 (7)
N40.7219 (3)0.3610 (3)0.6602 (3)0.0565 (8)
C50.1541 (3)0.2097 (3)0.2156 (3)0.0379 (7)
C60.2708 (4)0.3093 (3)0.2993 (3)0.0413 (7)
H6A0.30960.38450.27280.050*
C70.3308 (3)0.2995 (3)0.4209 (3)0.0397 (7)
H7A0.40950.36760.47500.048*
C80.1558 (5)0.3243 (4)0.0416 (3)0.0773 (12)
H8A0.09540.31430.04270.116*
H8B0.14720.40890.09520.116*
H8C0.26920.32020.03670.116*
C90.6160 (3)0.2519 (3)0.6011 (3)0.0379 (7)
C100.6416 (4)0.1628 (3)0.4945 (3)0.0439 (7)
H10A0.56460.08650.45610.053*
C110.7814 (4)0.1880 (3)0.4461 (3)0.0518 (8)
H11A0.80080.12910.37400.062*
C120.8924 (4)0.3007 (4)0.5044 (4)0.0620 (10)
H12A0.98880.32020.47330.074*
C130.8578 (4)0.3840 (4)0.6098 (4)0.0690 (11)
H13A0.93300.46120.64910.083*
C140.5114 (4)0.2464 (3)0.8003 (3)0.0475 (8)
H14A0.41040.25570.83370.057*
H14B0.58880.32820.83850.057*
C150.5797 (5)0.1331 (4)0.8390 (3)0.0655 (10)
H15A0.49580.05410.80980.079*
H15B0.67090.11600.79470.079*
C160.6378 (4)0.1525 (4)0.9788 (3)0.0599 (9)
C170.6878 (6)0.3086 (5)1.1817 (3)0.0847 (14)
H17A0.79710.28791.20140.102*
H17B0.61370.25711.22080.102*
C180.6888 (6)0.4523 (5)1.2312 (4)0.0952 (15)
H18A0.72420.47661.32230.143*
H18B0.76280.50241.19210.143*
H18C0.58010.47161.21150.143*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0435 (13)0.0743 (16)0.0496 (13)0.0010 (11)0.0100 (11)0.0272 (12)
N10.0462 (15)0.0471 (15)0.0367 (14)0.0005 (12)0.0029 (11)0.0137 (11)
C10.0357 (16)0.0398 (16)0.0391 (16)0.0055 (13)0.0030 (13)0.0108 (13)
N20.0542 (17)0.0577 (17)0.0418 (15)0.0017 (13)0.0019 (13)0.0212 (13)
C20.0284 (14)0.0419 (16)0.0388 (16)0.0093 (12)0.0059 (12)0.0143 (13)
O20.0681 (17)0.094 (2)0.0817 (19)0.0158 (15)0.0147 (14)0.0491 (17)
N30.0369 (14)0.0513 (15)0.0321 (13)0.0058 (11)0.0041 (11)0.0137 (11)
C30.0306 (15)0.0371 (16)0.0419 (16)0.0068 (12)0.0049 (12)0.0153 (13)
O30.103 (2)0.101 (2)0.0398 (14)0.0422 (17)0.0046 (14)0.0235 (14)
C40.0308 (15)0.0403 (16)0.0347 (15)0.0096 (12)0.0026 (12)0.0081 (13)
N40.0394 (15)0.0587 (18)0.0618 (18)0.0022 (13)0.0067 (13)0.0026 (14)
C50.0354 (16)0.0432 (17)0.0374 (16)0.0112 (13)0.0051 (13)0.0123 (14)
C60.0456 (17)0.0386 (16)0.0446 (17)0.0073 (14)0.0130 (14)0.0174 (14)
C70.0344 (16)0.0411 (17)0.0409 (17)0.0009 (13)0.0033 (13)0.0094 (13)
C80.105 (3)0.077 (3)0.052 (2)0.001 (2)0.005 (2)0.035 (2)
C90.0347 (15)0.0392 (16)0.0409 (16)0.0077 (13)0.0013 (13)0.0143 (13)
C100.0427 (18)0.0427 (18)0.0472 (18)0.0100 (14)0.0077 (14)0.0113 (15)
C110.050 (2)0.055 (2)0.058 (2)0.0177 (17)0.0181 (16)0.0182 (17)
C120.0394 (19)0.069 (2)0.086 (3)0.0152 (18)0.0211 (19)0.027 (2)
C130.043 (2)0.059 (2)0.094 (3)0.0072 (17)0.005 (2)0.009 (2)
C140.0495 (19)0.058 (2)0.0350 (17)0.0111 (15)0.0008 (14)0.0157 (15)
C150.081 (3)0.069 (2)0.051 (2)0.021 (2)0.0042 (19)0.0235 (18)
C160.052 (2)0.079 (3)0.055 (2)0.0171 (19)0.0002 (17)0.030 (2)
C170.091 (3)0.126 (4)0.039 (2)0.043 (3)0.001 (2)0.018 (2)
C180.086 (3)0.126 (4)0.061 (3)0.016 (3)0.003 (2)0.008 (3)
Geometric parameters (Å, º) top
O1—C11.223 (3)C7—H7A0.9300
N1—C41.412 (4)C8—H8A0.9600
N1—H1A0.8600C8—H8B0.9600
N1—H1B0.8600C8—H8C0.9600
C1—N31.371 (4)C9—C101.375 (4)
C1—C21.487 (4)C10—C111.363 (4)
N2—C51.386 (3)C10—H10A0.9300
N2—C81.424 (4)C11—C121.364 (5)
N2—H2A0.8600C11—H11A0.9300
C2—C71.377 (4)C12—C131.365 (5)
C2—C31.394 (4)C12—H12A0.9300
O2—C161.187 (4)C13—H13A0.9300
N3—C91.421 (4)C14—C151.494 (4)
N3—C141.469 (3)C14—H14A0.9700
C3—C41.378 (4)C14—H14B0.9700
C3—H3A0.9300C15—C161.492 (5)
O3—C161.333 (4)C15—H15A0.9700
O3—C171.450 (4)C15—H15B0.9700
C4—C51.409 (4)C17—C181.474 (6)
N4—C91.320 (4)C17—H17A0.9700
N4—C131.342 (4)C17—H17B0.9700
C5—C61.387 (4)C18—H18A0.9600
C6—C71.380 (4)C18—H18B0.9600
C6—H6A0.9300C18—H18C0.9600
C4—N1—H1A120.0C10—C9—N3122.2 (3)
C4—N1—H1B120.0C11—C10—C9119.1 (3)
H1A—N1—H1B120.0C11—C10—H10A120.5
O1—C1—N3119.9 (3)C9—C10—H10A120.5
O1—C1—C2120.6 (2)C10—C11—C12119.3 (3)
N3—C1—C2119.5 (2)C10—C11—H11A120.4
C5—N2—C8121.9 (3)C12—C11—H11A120.4
C5—N2—H2A119.0C11—C12—C13118.0 (3)
C8—N2—H2A119.0C11—C12—H12A121.0
C7—C2—C3118.6 (3)C13—C12—H12A121.0
C7—C2—C1122.7 (3)N4—C13—C12124.0 (3)
C3—C2—C1118.3 (2)N4—C13—H13A118.0
C1—N3—C9124.7 (2)C12—C13—H13A118.0
C1—N3—C14118.6 (2)N3—C14—C15113.1 (3)
C9—N3—C14116.4 (2)N3—C14—H14A109.0
C4—C3—C2121.9 (3)C15—C14—H14A109.0
C4—C3—H3A119.1N3—C14—H14B109.0
C2—C3—H3A119.1C15—C14—H14B109.0
C16—O3—C17117.4 (3)H14A—C14—H14B107.8
C3—C4—C5119.3 (3)C16—C15—C14115.9 (3)
C3—C4—N1120.7 (3)C16—C15—H15A108.3
C5—C4—N1120.0 (2)C14—C15—H15A108.3
C9—N4—C13116.7 (3)C16—C15—H15B108.3
N2—C5—C6122.1 (3)C14—C15—H15B108.3
N2—C5—C4119.5 (3)H15A—C15—H15B107.4
C6—C5—C4118.3 (2)O2—C16—O3123.7 (3)
C7—C6—C5121.6 (3)O2—C16—C15124.5 (4)
C7—C6—H6A119.2O3—C16—C15111.7 (3)
C5—C6—H6A119.2O3—C17—C18107.8 (3)
C2—C7—C6120.3 (3)O3—C17—H17A110.2
C2—C7—H7A119.8C18—C17—H17A110.2
C6—C7—H7A119.8O3—C17—H17B110.2
N2—C8—H8A109.5C18—C17—H17B110.2
N2—C8—H8B109.5H17A—C17—H17B108.5
H8A—C8—H8B109.5C17—C18—H18A109.5
N2—C8—H8C109.5C17—C18—H18B109.5
H8A—C8—H8C109.5H18A—C18—H18B109.5
H8B—C8—H8C109.5C17—C18—H18C109.5
N4—C9—C10123.0 (3)H18A—C18—H18C109.5
N4—C9—N3114.7 (3)H18B—C18—H18C109.5
O1—C1—C2—C7136.9 (3)C5—C6—C7—C20.3 (4)
N3—C1—C2—C740.0 (4)C13—N4—C9—C101.3 (5)
O1—C1—C2—C334.9 (4)C13—N4—C9—N3177.4 (3)
N3—C1—C2—C3148.3 (3)C1—N3—C9—N4140.7 (3)
O1—C1—N3—C9163.5 (3)C14—N3—C9—N445.4 (3)
C2—C1—N3—C919.6 (4)C1—N3—C9—C1043.2 (4)
O1—C1—N3—C1410.3 (4)C14—N3—C9—C10130.7 (3)
C2—C1—N3—C14166.6 (2)N4—C9—C10—C110.8 (4)
C7—C2—C3—C41.1 (4)N3—C9—C10—C11176.5 (3)
C1—C2—C3—C4173.2 (2)C9—C10—C11—C120.1 (5)
C2—C3—C4—C50.1 (4)C10—C11—C12—C130.0 (5)
C2—C3—C4—N1179.6 (2)C9—N4—C13—C121.3 (5)
C8—N2—C5—C68.7 (5)C11—C12—C13—N40.7 (6)
C8—N2—C5—C4174.3 (3)C1—N3—C14—C1598.0 (3)
C3—C4—C5—N2178.3 (2)C9—N3—C14—C1576.3 (3)
N1—C4—C5—N22.0 (4)N3—C14—C15—C16172.1 (3)
C3—C4—C5—C61.2 (4)C17—O3—C16—O20.1 (6)
N1—C4—C5—C6179.1 (2)C17—O3—C16—C15179.8 (3)
N2—C5—C6—C7178.4 (3)C14—C15—C16—O2173.4 (4)
C4—C5—C6—C71.4 (4)C14—C15—C16—O36.6 (5)
C3—C2—C7—C60.9 (4)C16—O3—C17—C18174.3 (3)
C1—C2—C7—C6172.7 (2)
Hydrogen-bond geometry (Å, º) top
Cg2 is the centroid of the C2–C7 benzene ring.
D—H···AD—HH···AD···AD—H···A
N1—H1A···O1i0.862.313.035 (3)142
N1—H1B···O2ii0.862.413.018 (4)128
C12—H12A···Cg2iii0.932.793.566 (4)142
Symmetry codes: (i) x, y, z+1; (ii) x1, y, z1; (iii) x+1, y, z.
 

Acknowledgements

We are very grateful for the financial support from the National Natural Science Foundation of China (grant No. 21371031).

References

First citationChen, Y., Liang, J., Chen, H.-S. & Yuan, L. (2013). Heterocycles, 87, 1699–1710.  Web of Science CrossRef CAS Google Scholar
First citationFarrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationRigaku. (2005). CrystalClear. Rigaku Corporation, Tokyo, Japan.  Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoIUCrDATA
ISSN: 2414-3146
Follow IUCr Journals
Sign up for e-alerts
Follow IUCr on Twitter
Follow us on facebook
Sign up for RSS feeds