Diethyl 4-(biphenyl-4-yl)-2,6-dimethyl-1,4-di-hydro-pyridine-3,5-di-carboxyl-ate.

The title compound, C25H27NO4, has a flattened di-hydro-pyridine ring. The benzene and phenyl rings are synclinal to one another, forming a dihedral angle of 49.82 (8)°; the axis of the biphenyl rings makes an 81.05 (9)° angle to the plane of the di-hydro-pyridine ring. In the crystal, N-H⋯O hydrogen bonds link the mol-ecules into chain motifs running along the a-axis direction. The chains are cross-linked by C-H⋯O inter-actions, forming sheet motifs running slightly off the (110) plane, together with an intermolecular interaction between head-to tail biphenyl groups, thus making the whole crystal packing a three-dimensional network. Intra-molecular C-H⋯O hydrogen bonds are also observed.

Related literature

For general structure–activity relationship studies of 1,4-di­hydro­pyridines (DHPs) as calcium channel modulators, see: Bossert et al. (1981 ▶); Triggle (2003 ▶). For binding studies of DHPs to multiple drug resistant protein 1 (MDR1), see: Abe et al. (1995 ▶); Cole et al. (1989 ▶); Tasaki et al. (1995 ▶); Vanhoefer et al. (1999 ▶); Tolomero et al. (1994 ▶); Cindric et al. (2010 ▶).

Experimental

Crystal data

C25H27NO4

M = 405.47

Triclinic,

a = 7.3431 (3) Å

b = 10.6075 (4) Å

c = 13.8449 (6) Å

α = 85.762 (3)°

β = 88.124 (3)°

γ = 73.530 (2)°

V = 1031.25 (7) Å3

Z = 2

Mo Kα radiation

μ = 0.09 mm−1

T = 100 K

0.15 × 0.14 × 0.13 mm

Data collection

Bruker SMART BREEZE CCD diffractometer

Absorption correction: multi-scan (SADABS; Bruker, 2012 ▶) T min = 0.919, T max = 1.000

19956 measured reflections

4752 independent reflections

2983 reflections with I > 2σ(I)

R int = 0.072

Refinement

R[F 2 > 2σ(F 2)] = 0.062

wR(F 2) = 0.149

S = 1.02

4752 reflections

279 parameters

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.43 e Å−3

Δρmin = −0.37 e Å−3

Data collection: APEX2 (Bruker, 2012 ▶); cell refinement: SAINT (Bruker, 2012 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: OLEX2 (Dolomanov et al., 2009 ▶); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009 ▶).

Crystal structure: contains datablock(s) I. DOI: 10.1107/S1600536814013294/zl2590sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814013294/zl2590Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S1600536814013294/zl2590Isup3.cml

Additional supporting information: crystallographic information; 3D view; checkCIF report

C25H27NO4	Z = 2
Mr = 405.47	F(000) = 432
Triclinic, P1	Dx = 1.306 Mg m−3
a = 7.3431 (3) Å	Mo Kα radiation, λ = 0.71073 Å
b = 10.6075 (4) Å	Cell parameters from 5122 reflections
c = 13.8449 (6) Å	θ = 2.4–27.4°
α = 85.762 (3)°	µ = 0.09 mm−1
β = 88.124 (3)°	T = 100 K
γ = 73.530 (2)°	Prism, pale white
V = 1031.25 (7) Å3	0.15 × 0.14 × 0.13 mm

Bruker SMART BREEZE CCD diffractometer	2983 reflections with I > 2σ(I)
Radiation source: 2 kW sealed X-ray tube	Rint = 0.072
φ and ω scans	θmax = 27.6°, θmin = 2.0°
Absorption correction: multi-scan (SADABS; Bruker, 2012)	h = −9→9
Tmin = 0.919, Tmax = 1.000	k = −13→13
19956 measured reflections	l = −17→18
4752 independent reflections

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.062	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.149	w = 1/[σ2(Fo2) + (0.0537P)2 + 0.8331P] where P = (Fo2 + 2Fc2)/3
S = 1.02	(Δ/σ)max = 0.001
4752 reflections	Δρmax = 0.43 e Å−3
279 parameters	Δρmin = −0.37 e Å−3
0 restraints

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.

	x	y	z	Uiso*/Ueq
O3	0.1263 (2)	0.73985 (17)	0.98682 (13)	0.0183 (4)
O1	0.4574 (2)	0.44644 (15)	0.75695 (12)	0.0149 (4)
O4	0.2751 (2)	0.84869 (17)	1.07429 (13)	0.0191 (4)
N1	0.7805 (3)	0.68215 (19)	0.92579 (15)	0.0127 (5)
O2	0.7739 (2)	0.38137 (18)	0.73785 (14)	0.0248 (5)
C3	0.4394 (3)	0.6641 (2)	0.85636 (17)	0.0111 (5)
H3	0.3408	0.6153	0.8619	0.013*
C4	0.4521 (3)	0.7191 (2)	0.95378 (17)	0.0115 (5)
C20	0.1965 (3)	1.0952 (2)	0.55708 (17)	0.0118 (5)
C14	0.3787 (3)	0.7763 (2)	0.77713 (17)	0.0107 (5)
C25	0.2602 (3)	1.0854 (2)	0.46091 (18)	0.0156 (5)
H25	0.3384	1.0037	0.4406	0.019*
C1	0.7918 (3)	0.5861 (2)	0.86166 (17)	0.0122 (5)
C18	0.2529 (3)	0.8563 (2)	0.61659 (18)	0.0141 (5)
H18	0.2085	0.8383	0.5569	0.017*
C5	0.6197 (3)	0.7352 (2)	0.98050 (17)	0.0112 (5)
C2	0.6293 (3)	0.5673 (2)	0.83079 (17)	0.0118 (5)
C7	0.2713 (3)	0.7670 (2)	1.00548 (18)	0.0136 (5)
C21	0.0758 (3)	1.2152 (2)	0.58379 (18)	0.0138 (5)
H21	0.0290	1.2231	0.6485	0.017*
C22	0.0236 (3)	1.3226 (2)	0.51739 (19)	0.0167 (6)
H22	−0.0601	1.4031	0.5365	0.020*
C17	0.2607 (3)	0.9835 (2)	0.63075 (17)	0.0107 (5)
C16	0.3313 (3)	1.0043 (2)	0.71876 (18)	0.0144 (5)
H16	0.3398	1.0897	0.7301	0.017*
C6	0.6587 (3)	0.8067 (2)	1.06364 (18)	0.0163 (6)
H6A	0.7962	0.7883	1.0711	0.025*
H6B	0.6033	0.7768	1.1233	0.025*
H6C	0.6021	0.9017	1.0508	0.025*
C19	0.3093 (3)	0.7555 (2)	0.68872 (18)	0.0139 (5)
H19	0.3004	0.6701	0.6776	0.017*
C15	0.3893 (3)	0.9031 (2)	0.78989 (18)	0.0125 (5)
H15	0.4374	0.9204	0.8488	0.015*
C13	0.9930 (3)	0.5135 (3)	0.8374 (2)	0.0204 (6)
H13A	1.0506	0.5717	0.7965	0.031*
H13B	0.9946	0.4360	0.8025	0.031*
H13C	1.0654	0.4853	0.8972	0.031*
C8	0.0994 (3)	0.9041 (2)	1.12773 (18)	0.0152 (5)
H8A	0.0608	0.8337	1.1667	0.018*
H8B	−0.0041	0.9496	1.0825	0.018*
C10	0.6336 (3)	0.4574 (2)	0.77147 (18)	0.0146 (5)
C9	0.1404 (4)	1.0005 (2)	1.19262 (19)	0.0195 (6)
H9A	0.1838	1.0672	1.1532	0.029*
H9B	0.2395	0.9535	1.2386	0.029*
H9C	0.0246	1.0433	1.2283	0.029*
C23	0.0929 (4)	1.3132 (2)	0.42313 (19)	0.0177 (6)
H23	0.0603	1.3878	0.3781	0.021*
C24	0.2102 (3)	1.1940 (2)	0.39484 (19)	0.0168 (6)
H24	0.2564	1.1868	0.3300	0.020*
C11	0.4471 (4)	0.3420 (2)	0.69640 (18)	0.0176 (6)
H11A	0.3249	0.3213	0.7091	0.021*
H11B	0.5507	0.2616	0.7141	0.021*
C12	0.4631 (4)	0.3793 (3)	0.59046 (19)	0.0245 (6)
H12A	0.4454	0.3093	0.5526	0.037*
H12B	0.5891	0.3912	0.5763	0.037*
H12C	0.3654	0.4618	0.5733	0.037*
H1	0.893 (4)	0.696 (3)	0.9411 (19)	0.023 (8)*

	U11	U22	U33	U12	U13	U23
O3	0.0103 (9)	0.0255 (10)	0.0221 (11)	−0.0085 (8)	0.0015 (7)	−0.0084 (8)
O1	0.0152 (9)	0.0113 (9)	0.0194 (10)	−0.0046 (7)	0.0007 (7)	−0.0057 (7)
O4	0.0115 (9)	0.0269 (10)	0.0210 (10)	−0.0064 (8)	0.0055 (7)	−0.0145 (8)
N1	0.0078 (10)	0.0152 (11)	0.0168 (12)	−0.0054 (9)	0.0013 (8)	−0.0049 (9)
O2	0.0154 (9)	0.0238 (10)	0.0328 (12)	0.0018 (8)	−0.0007 (8)	−0.0158 (9)
C3	0.0091 (11)	0.0108 (12)	0.0145 (13)	−0.0040 (9)	−0.0004 (10)	−0.0026 (10)
C4	0.0122 (12)	0.0108 (12)	0.0110 (13)	−0.0026 (9)	0.0003 (9)	0.0000 (9)
C20	0.0106 (12)	0.0127 (12)	0.0127 (13)	−0.0044 (10)	−0.0018 (10)	−0.0002 (10)
C14	0.0068 (11)	0.0106 (12)	0.0130 (13)	0.0005 (9)	0.0019 (9)	−0.0018 (10)
C25	0.0126 (12)	0.0170 (13)	0.0181 (14)	−0.0047 (10)	−0.0010 (10)	−0.0039 (11)
C1	0.0108 (12)	0.0119 (12)	0.0126 (13)	−0.0016 (10)	−0.0005 (10)	0.0021 (10)
C18	0.0143 (12)	0.0145 (13)	0.0128 (14)	−0.0018 (10)	−0.0022 (10)	−0.0052 (10)
C5	0.0126 (12)	0.0093 (11)	0.0118 (13)	−0.0038 (9)	−0.0001 (10)	0.0011 (10)
C2	0.0131 (12)	0.0111 (12)	0.0120 (13)	−0.0050 (10)	0.0003 (10)	0.0006 (10)
C7	0.0142 (12)	0.0131 (12)	0.0136 (14)	−0.0044 (10)	−0.0007 (10)	0.0012 (10)
C21	0.0149 (12)	0.0138 (12)	0.0126 (13)	−0.0033 (10)	−0.0010 (10)	−0.0028 (10)
C22	0.0154 (13)	0.0113 (12)	0.0229 (15)	−0.0020 (10)	−0.0035 (11)	−0.0040 (11)
C17	0.0076 (11)	0.0116 (12)	0.0119 (13)	−0.0013 (9)	0.0018 (9)	−0.0011 (10)
C16	0.0161 (13)	0.0114 (12)	0.0168 (14)	−0.0051 (10)	0.0004 (10)	−0.0032 (10)
C6	0.0125 (12)	0.0205 (13)	0.0167 (14)	−0.0050 (10)	−0.0001 (10)	−0.0040 (11)
C19	0.0129 (12)	0.0091 (12)	0.0191 (14)	−0.0017 (10)	0.0003 (10)	−0.0020 (10)
C15	0.0131 (12)	0.0147 (12)	0.0109 (13)	−0.0050 (10)	−0.0022 (10)	−0.0033 (10)
C13	0.0133 (13)	0.0238 (14)	0.0220 (15)	−0.0003 (11)	0.0000 (11)	−0.0078 (12)
C8	0.0102 (12)	0.0200 (13)	0.0145 (14)	−0.0024 (10)	0.0040 (10)	−0.0048 (11)
C10	0.0147 (13)	0.0121 (12)	0.0156 (14)	−0.0016 (10)	−0.0009 (10)	0.0002 (10)
C9	0.0163 (13)	0.0194 (14)	0.0230 (16)	−0.0041 (11)	0.0036 (11)	−0.0089 (11)
C23	0.0221 (14)	0.0155 (13)	0.0163 (14)	−0.0075 (11)	−0.0065 (11)	0.0048 (11)
C24	0.0172 (13)	0.0244 (14)	0.0108 (13)	−0.0091 (11)	−0.0004 (10)	−0.0011 (11)
C11	0.0228 (14)	0.0110 (12)	0.0203 (15)	−0.0052 (11)	0.0002 (11)	−0.0081 (11)
C12	0.0253 (15)	0.0329 (16)	0.0195 (15)	−0.0135 (13)	−0.0007 (12)	−0.0067 (12)

O3—C7	1.219 (3)	C21—C22	1.382 (3)
O1—C10	1.354 (3)	C22—H22	0.9500
O1—C11	1.458 (3)	C22—C23	1.385 (4)
O4—C7	1.340 (3)	C17—C16	1.396 (3)
O4—C8	1.459 (3)	C16—H16	0.9500
N1—C1	1.383 (3)	C16—C15	1.385 (3)
N1—C5	1.383 (3)	C6—H6A	0.9800
N1—H1	0.91 (3)	C6—H6B	0.9800
O2—C10	1.217 (3)	C6—H6C	0.9800
C3—H3	1.0000	C19—H19	0.9500
C3—C4	1.525 (3)	C15—H15	0.9500
C3—C14	1.536 (3)	C13—H13A	0.9800
C3—C2	1.527 (3)	C13—H13B	0.9800
C4—C5	1.356 (3)	C13—H13C	0.9800
C4—C7	1.464 (3)	C8—H8A	0.9900
C20—C25	1.398 (3)	C8—H8B	0.9900
C20—C21	1.396 (3)	C8—C9	1.506 (3)
C20—C17	1.484 (3)	C9—H9A	0.9800
C14—C19	1.397 (3)	C9—H9B	0.9800
C14—C15	1.392 (3)	C9—H9C	0.9800
C25—H25	0.9500	C23—H23	0.9500
C25—C24	1.388 (4)	C23—C24	1.388 (3)
C1—C2	1.352 (3)	C24—H24	0.9500
C1—C13	1.500 (3)	C11—H11A	0.9900
C18—H18	0.9500	C11—H11B	0.9900
C18—C17	1.395 (3)	C11—C12	1.500 (4)
C18—C19	1.389 (3)	C12—H12A	0.9800
C5—C6	1.502 (3)	C12—H12B	0.9800
C2—C10	1.468 (3)	C12—H12C	0.9800
C21—H21	0.9500
C10—O1—C11	115.95 (18)	C5—C6—H6B	109.5
C7—O4—C8	117.92 (18)	C5—C6—H6C	109.5
C1—N1—H1	115.9 (17)	H6A—C6—H6B	109.5
C5—N1—C1	123.2 (2)	H6A—C6—H6C	109.5
C5—N1—H1	119.4 (17)	H6B—C6—H6C	109.5
C4—C3—H3	108.3	C14—C19—H19	119.1
C4—C3—C14	110.48 (18)	C18—C19—C14	121.8 (2)
C4—C3—C2	110.09 (19)	C18—C19—H19	119.1
C14—C3—H3	108.3	C14—C15—H15	119.2
C2—C3—H3	108.3	C16—C15—C14	121.6 (2)
C2—C3—C14	111.20 (19)	C16—C15—H15	119.2
C5—C4—C3	119.3 (2)	C1—C13—H13A	109.5
C5—C4—C7	124.8 (2)	C1—C13—H13B	109.5
C7—C4—C3	115.4 (2)	C1—C13—H13C	109.5
C25—C20—C17	121.4 (2)	H13A—C13—H13B	109.5
C21—C20—C25	118.4 (2)	H13A—C13—H13C	109.5
C21—C20—C17	120.2 (2)	H13B—C13—H13C	109.5
C19—C14—C3	121.1 (2)	O4—C8—H8A	110.5
C15—C14—C3	121.9 (2)	O4—C8—H8B	110.5
C15—C14—C19	117.0 (2)	O4—C8—C9	106.34 (19)
C20—C25—H25	119.7	H8A—C8—H8B	108.7
C24—C25—C20	120.5 (2)	C9—C8—H8A	110.5
C24—C25—H25	119.7	C9—C8—H8B	110.5
N1—C1—C13	112.5 (2)	O1—C10—C2	112.0 (2)
C2—C1—N1	118.8 (2)	O2—C10—O1	121.3 (2)
C2—C1—C13	128.7 (2)	O2—C10—C2	126.7 (2)
C17—C18—H18	119.6	C8—C9—H9A	109.5
C19—C18—H18	119.6	C8—C9—H9B	109.5
C19—C18—C17	120.8 (2)	C8—C9—H9C	109.5
N1—C5—C6	112.8 (2)	H9A—C9—H9B	109.5
C4—C5—N1	118.6 (2)	H9A—C9—H9C	109.5
C4—C5—C6	128.6 (2)	H9B—C9—H9C	109.5
C1—C2—C3	119.2 (2)	C22—C23—H23	120.2
C1—C2—C10	120.9 (2)	C22—C23—C24	119.6 (2)
C10—C2—C3	119.9 (2)	C24—C23—H23	120.2
O3—C7—O4	121.7 (2)	C25—C24—C23	120.3 (2)
O3—C7—C4	124.1 (2)	C25—C24—H24	119.9
O4—C7—C4	114.2 (2)	C23—C24—H24	119.9
C20—C21—H21	119.5	O1—C11—H11A	109.1
C22—C21—C20	120.9 (2)	O1—C11—H11B	109.1
C22—C21—H21	119.5	O1—C11—C12	112.4 (2)
C21—C22—H22	119.9	H11A—C11—H11B	107.9
C21—C22—C23	120.2 (2)	C12—C11—H11A	109.1
C23—C22—H22	119.9	C12—C11—H11B	109.1
C18—C17—C20	122.8 (2)	C11—C12—H12A	109.5
C18—C17—C16	117.5 (2)	C11—C12—H12B	109.5
C16—C17—C20	119.7 (2)	C11—C12—H12C	109.5
C17—C16—H16	119.3	H12A—C12—H12B	109.5
C15—C16—C17	121.3 (2)	H12A—C12—H12C	109.5
C15—C16—H16	119.3	H12B—C12—H12C	109.5
C5—C6—H6A	109.5
N1—C1—C2—C3	8.3 (3)	C14—C3—C2—C10	−87.0 (3)
N1—C1—C2—C10	−173.2 (2)	C25—C20—C21—C22	−1.3 (3)
C3—C4—C5—N1	−10.0 (3)	C25—C20—C17—C18	−50.9 (3)
C3—C4—C5—C6	169.1 (2)	C25—C20—C17—C16	129.5 (2)
C3—C4—C7—O3	16.6 (3)	C1—N1—C5—C4	−17.3 (3)
C3—C4—C7—O4	−161.2 (2)	C1—N1—C5—C6	163.4 (2)
C3—C14—C19—C18	179.7 (2)	C1—C2—C10—O1	173.1 (2)
C3—C14—C15—C16	−178.9 (2)	C1—C2—C10—O2	−6.4 (4)
C3—C2—C10—O1	−8.3 (3)	C18—C17—C16—C15	−0.8 (3)
C3—C2—C10—O2	172.2 (2)	C5—N1—C1—C2	18.3 (4)
C4—C3—C14—C19	−163.0 (2)	C5—N1—C1—C13	−160.6 (2)
C4—C3—C14—C15	16.7 (3)	C5—C4—C7—O3	−171.8 (2)
C4—C3—C2—C1	−31.2 (3)	C5—C4—C7—O4	10.5 (3)
C4—C3—C2—C10	150.2 (2)	C2—C3—C4—C5	32.1 (3)
C20—C25—C24—C23	−1.3 (4)	C2—C3—C4—C7	−155.7 (2)
C20—C21—C22—C23	−0.9 (4)	C2—C3—C14—C19	74.4 (3)
C20—C17—C16—C15	178.8 (2)	C2—C3—C14—C15	−105.9 (2)
C14—C3—C4—C5	−91.1 (3)	C7—O4—C8—C9	−174.9 (2)
C14—C3—C4—C7	81.1 (2)	C7—C4—C5—N1	178.6 (2)
C14—C3—C2—C1	91.6 (3)	C7—C4—C5—C6	−2.3 (4)

D—H···A	D—H	H···A	D···A	D—H···A
C21—H21···O2i	0.95	2.50	3.256 (3)	137
C6—H6A···O3ii	0.98	2.59	3.452 (3)	147
C19—H19···O1	0.95	2.51	3.227 (3)	132
C13—H13B···O2	0.98	2.11	2.857 (3)	131
C8—H8A···O2iii	0.99	2.55	3.344 (3)	137
N1—H1···O3ii	0.91 (3)	2.03 (3)	2.938 (3)	173 (2)

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C21—H21⋯O2i	0.95	2.50	3.256 (3)	137
C6—H6A⋯O3ii	0.98	2.59	3.452 (3)	147
C19—H19⋯O1	0.95	2.51	3.227 (3)	132
C13—H13B⋯O2	0.98	2.11	2.857 (3)	131
C8—H8A⋯O2iii	0.99	2.55	3.344 (3)	137
N1—H1⋯O3ii	0.91 (3)	2.03 (3)	2.938 (3)	173 (2)

Symmetry codes: (i) ; (ii) ; (iii) .