Ethyl 2-amino-4-(4-bromo-phen-yl)-6-meth-oxy-4H-benzo[h]chromene-3-carboxyl-ate.

In the title compound, C23H20BrNO4, the pyran ring has a flattened boat conformation with the O and methine C atoms lying to one side of the plane [0.160 (5) and 0.256 (6) Å, respectively] defined by the remaining atoms. Nevertheless, the 4H-benzo[h]chromene ring system approximates a plane (r.m.s. deviation = 0.116 Å) with the bromo-benzene ring almost perpendicular [dihedral angle = 83.27 (16)°] and the ester group coplanar [C-C-C-O = 3.4 (5)°]; the meth-oxy substituent is also coplanar [C-O-C-C = 174.5 (3)°]. In addition to an intra-molecular N-H⋯O(ester carbon-yl) hydrogen bond, the ester carbonyl O atom also forms an inter-molecular N-H⋯O hydrogen bond with the second amine H atom, generating a zigzag supra-molecular chain along the c axis in the crystal packing. The chains are linked into layers in the bc plane by N-H⋯Br hydrogen bonds, and these layers are consolidated into a three-dimensional architecture by C-H⋯π inter-actions.

Related literature

For background to the pharmaceutical activity of 4H-chromene and its derivatives, see: Abd-El-Aziz et al. (2004 ▶, 2007 ▶); Kemnitzer et al. (2007 ▶); Alvey et al. (2009 ▶). For the isostructural 4-fluoro analogue, see: El-Agrody et al. (2012 ▶).

Experimental

Crystal data

C23H20BrNO4

M = 454.31

Monoclinic,

a = 13.1543 (14) Å

b = 16.8110 (18) Å

c = 9.3672 (12) Å

β = 96.628 (10)°

V = 2057.6 (4) Å3

Z = 4

Mo Kα radiation

μ = 2.03 mm−1

T = 295 K

0.30 × 0.20 × 0.03 mm

Data collection

Agilent SuperNova Dual diffractometer with an Atlas detector

Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011 ▶) T min = 0.828, T max = 1.000

12041 measured reflections

4740 independent reflections

2533 reflections with I > 2σ(I)

R int = 0.054

Refinement

R[F 2 > 2σ(F 2)] = 0.060

wR(F 2) = 0.164

S = 1.02

4740 reflections

270 parameters

2 restraints

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.91 e Å−3

Δρmin = −0.90 e Å−3

Data collection: CrysAlis PRO (Agilent, 2011 ▶); 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: ORTEP-3 for Windows (Farrugia, 2012 ▶) and DIAMOND (Brandenburg, 2006 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Click here for additional data file.

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S160053681300490X/hg5295sup1.cif

Click here for additional data file.

Structure factors: contains datablock(s) I. DOI: 10.1107/S160053681300490X/hg5295Isup2.hkl

Click here for additional data file.

Supplementary material file. DOI: 10.1107/S160053681300490X/hg5295Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C23H20BrNO4	F(000) = 928
Mr = 454.31	Dx = 1.467 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 1932 reflections
a = 13.1543 (14) Å	θ = 2.8–27.5°
b = 16.8110 (18) Å	µ = 2.03 mm−1
c = 9.3672 (12) Å	T = 295 K
β = 96.628 (10)°	Plate, light-orange
V = 2057.6 (4) Å3	0.30 × 0.20 × 0.03 mm
Z = 4

Agilent SuperNova Dual diffractometer with an Atlas detector	4740 independent reflections
Radiation source: SuperNova (Mo) X-ray Source	2533 reflections with I > 2σ(I)
Mirror monochromator	Rint = 0.054
Detector resolution: 10.4041 pixels mm-1	θmax = 27.6°, θmin = 2.9°
ω scan	h = −16→17
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011)	k = −21→21
Tmin = 0.828, Tmax = 1.000	l = −7→12
12041 measured reflections

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)] = 0.060	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.164	H atoms treated by a mixture of independent and constrained refinement
S = 1.02	w = 1/[σ2(Fo2) + (0.0575P)2 + 0.7996P] where P = (Fo2 + 2Fc2)/3
4740 reflections	(Δ/σ)max = 0.001
270 parameters	Δρmax = 0.91 e Å−3
2 restraints	Δρmin = −0.90 e Å−3

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
Br1	0.04105 (4)	0.70821 (4)	0.50571 (7)	0.0900 (3)
O1	0.30720 (18)	0.30429 (15)	0.7238 (3)	0.0464 (7)
O2	0.1283 (2)	0.34197 (17)	1.0635 (3)	0.0539 (7)
O3	0.1749 (2)	0.47024 (17)	1.0602 (3)	0.0558 (7)
O4	0.6285 (2)	0.50690 (18)	0.6512 (3)	0.0634 (8)
N1	0.1869 (3)	0.2527 (2)	0.8418 (4)	0.0538 (9)
H2	0.138 (3)	0.260 (4)	0.897 (5)	0.11 (2)*
H1	0.182 (3)	0.2203 (18)	0.768 (3)	0.044 (12)*
C1	0.3874 (3)	0.3580 (2)	0.7136 (4)	0.0397 (9)
C2	0.4654 (3)	0.3302 (2)	0.6337 (4)	0.0399 (9)
C3	0.4637 (3)	0.2537 (2)	0.5709 (4)	0.0447 (9)
H3	0.4095	0.2194	0.5807	0.054*
C4	0.5416 (3)	0.2300 (3)	0.4959 (4)	0.0533 (11)
H4	0.5404	0.1792	0.4562	0.064*
C5	0.6228 (3)	0.2812 (3)	0.4783 (5)	0.0613 (12)
H5	0.6752	0.2644	0.4267	0.074*
C6	0.6260 (3)	0.3553 (3)	0.5359 (5)	0.0579 (12)
H6	0.6802	0.3889	0.5223	0.069*
C7	0.5480 (3)	0.3824 (2)	0.6167 (4)	0.0436 (9)
C8	0.5483 (3)	0.4599 (2)	0.6797 (4)	0.0464 (10)
C9	0.4730 (3)	0.4824 (2)	0.7582 (4)	0.0463 (10)
H9	0.4756	0.5325	0.8007	0.056*
C10	0.3900 (3)	0.4308 (2)	0.7768 (4)	0.0409 (9)
C11	0.3054 (3)	0.4576 (2)	0.8616 (4)	0.0428 (9)
H11	0.3369	0.4829	0.9501	0.051*
C12	0.2446 (3)	0.3864 (2)	0.9034 (4)	0.0390 (9)
C13	0.2453 (3)	0.3168 (2)	0.8286 (4)	0.0394 (9)
C14	0.1773 (3)	0.3946 (2)	1.0137 (4)	0.0428 (9)
C15	0.1070 (4)	0.4882 (3)	1.1673 (5)	0.0741 (14)
H15A	0.1343	0.4669	1.2601	0.089*
H15B	0.0400	0.4652	1.1401	0.089*
C16	0.0999 (5)	0.5766 (3)	1.1742 (6)	0.097 (2)
H16A	0.0550	0.5913	1.2435	0.146*
H16B	0.0736	0.5968	1.0814	0.146*
H16C	0.1667	0.5984	1.2020	0.146*
C17	0.2379 (3)	0.5190 (2)	0.7770 (4)	0.0426 (9)
C18	0.1791 (3)	0.4979 (2)	0.6511 (5)	0.0516 (10)
H18	0.1789	0.4454	0.6199	0.062*
C19	0.1203 (3)	0.5538 (3)	0.5709 (5)	0.0582 (12)
H19	0.0813	0.5392	0.4858	0.070*
C20	0.1202 (3)	0.6312 (3)	0.6184 (5)	0.0568 (12)
C21	0.1771 (4)	0.6536 (3)	0.7419 (5)	0.0659 (13)
H21	0.1764	0.7061	0.7731	0.079*
C22	0.2362 (3)	0.5972 (3)	0.8208 (5)	0.0588 (12)
H22	0.2756	0.6124	0.9052	0.071*
C23	0.6286 (3)	0.5869 (3)	0.6996 (5)	0.0624 (12)
H23A	0.6879	0.6138	0.6725	0.094*
H23B	0.6302	0.5878	0.8023	0.094*
H23C	0.5680	0.6133	0.6566	0.094*

	U11	U22	U33	U12	U13	U23
Br1	0.0945 (4)	0.0850 (5)	0.0981 (5)	0.0486 (3)	0.0437 (3)	0.0394 (3)
O1	0.0453 (14)	0.0431 (16)	0.0537 (18)	−0.0112 (12)	0.0179 (12)	−0.0067 (13)
O2	0.0601 (17)	0.0524 (19)	0.0521 (18)	−0.0043 (14)	0.0187 (13)	0.0031 (14)
O3	0.0770 (19)	0.0445 (17)	0.0495 (18)	0.0043 (14)	0.0229 (14)	−0.0045 (14)
O4	0.0519 (17)	0.058 (2)	0.083 (2)	−0.0210 (15)	0.0179 (14)	−0.0057 (17)
N1	0.058 (2)	0.046 (2)	0.062 (3)	−0.0103 (19)	0.0252 (19)	−0.0082 (19)
C1	0.0367 (19)	0.042 (2)	0.041 (2)	−0.0061 (17)	0.0063 (16)	0.0040 (18)
C2	0.0375 (19)	0.042 (2)	0.040 (2)	0.0000 (17)	0.0032 (15)	0.0032 (18)
C3	0.043 (2)	0.043 (2)	0.047 (2)	−0.0030 (19)	0.0062 (17)	−0.0026 (19)
C4	0.059 (3)	0.050 (3)	0.052 (3)	0.004 (2)	0.012 (2)	−0.006 (2)
C5	0.049 (3)	0.069 (3)	0.068 (3)	0.001 (2)	0.019 (2)	−0.008 (3)
C6	0.046 (2)	0.063 (3)	0.068 (3)	−0.007 (2)	0.018 (2)	−0.002 (2)
C7	0.036 (2)	0.047 (2)	0.048 (2)	−0.0049 (18)	0.0054 (16)	0.0043 (19)
C8	0.041 (2)	0.047 (2)	0.051 (3)	−0.0103 (18)	0.0025 (17)	0.001 (2)
C9	0.045 (2)	0.040 (2)	0.054 (3)	−0.0053 (18)	0.0043 (18)	−0.0024 (19)
C10	0.039 (2)	0.041 (2)	0.041 (2)	−0.0011 (17)	0.0025 (16)	0.0002 (18)
C11	0.049 (2)	0.041 (2)	0.039 (2)	−0.0021 (18)	0.0034 (16)	−0.0040 (18)
C12	0.043 (2)	0.036 (2)	0.039 (2)	0.0007 (17)	0.0069 (16)	0.0008 (17)
C13	0.0392 (19)	0.037 (2)	0.043 (2)	−0.0039 (17)	0.0095 (16)	0.0037 (18)
C14	0.044 (2)	0.044 (2)	0.040 (2)	0.0026 (19)	0.0023 (17)	0.0041 (19)
C15	0.102 (4)	0.071 (4)	0.055 (3)	0.018 (3)	0.029 (3)	−0.008 (3)
C16	0.151 (6)	0.073 (4)	0.073 (4)	0.044 (4)	0.037 (4)	−0.005 (3)
C17	0.046 (2)	0.035 (2)	0.048 (2)	−0.0047 (17)	0.0116 (17)	−0.0024 (18)
C18	0.060 (2)	0.038 (2)	0.056 (3)	0.001 (2)	0.007 (2)	0.001 (2)
C19	0.056 (3)	0.064 (3)	0.054 (3)	0.002 (2)	0.007 (2)	0.010 (2)
C20	0.056 (3)	0.050 (3)	0.070 (3)	0.018 (2)	0.031 (2)	0.016 (2)
C21	0.093 (3)	0.038 (3)	0.072 (3)	0.014 (2)	0.032 (3)	0.000 (2)
C22	0.077 (3)	0.042 (3)	0.058 (3)	0.000 (2)	0.012 (2)	−0.008 (2)
C23	0.061 (3)	0.050 (3)	0.074 (3)	−0.016 (2)	−0.001 (2)	0.008 (2)

Br1—C20	1.903 (4)	C9—H9	0.9300
O1—C13	1.362 (4)	C10—C11	1.508 (5)
O1—C1	1.400 (4)	C11—C12	1.517 (5)
O2—C14	1.218 (4)	C11—C17	1.524 (5)
O3—C14	1.346 (5)	C11—H11	0.9800
O3—C15	1.450 (5)	C12—C13	1.364 (5)
O4—C8	1.369 (4)	C12—C14	1.442 (5)
O4—C23	1.419 (5)	C15—C16	1.489 (7)
N1—C13	1.338 (5)	C15—H15A	0.9700
N1—H2	0.876 (10)	C15—H15B	0.9700
N1—H1	0.878 (10)	C16—H16A	0.9600
C1—C10	1.359 (5)	C16—H16B	0.9600
C1—C2	1.417 (5)	C16—H16C	0.9600
C2—C3	1.413 (5)	C17—C22	1.378 (5)
C2—C7	1.420 (5)	C17—C18	1.380 (5)
C3—C4	1.366 (5)	C18—C19	1.382 (6)
C3—H3	0.9300	C18—H18	0.9300
C4—C5	1.397 (6)	C19—C20	1.375 (6)
C4—H4	0.9300	C19—H19	0.9300
C5—C6	1.355 (6)	C20—C21	1.356 (6)
C5—H5	0.9300	C21—C22	1.384 (6)
C6—C7	1.418 (6)	C21—H21	0.9300
C6—H6	0.9300	C22—H22	0.9300
C7—C8	1.430 (6)	C23—H23A	0.9600
C8—C9	1.354 (6)	C23—H23B	0.9600
C9—C10	1.421 (5)	C23—H23C	0.9600
C13—O1—C1	117.9 (3)	C14—C12—C11	119.7 (3)
C14—O3—C15	117.4 (3)	N1—C13—O1	109.9 (3)
C8—O4—C23	117.3 (3)	N1—C13—C12	127.2 (4)
C13—N1—H2	114 (4)	O1—C13—C12	122.9 (3)
C13—N1—H1	115 (3)	O2—C14—O3	121.9 (4)
H2—N1—H1	125 (5)	O2—C14—C12	126.8 (4)
C10—C1—O1	122.1 (3)	O3—C14—C12	111.2 (4)
C10—C1—C2	123.0 (3)	O3—C15—C16	106.5 (4)
O1—C1—C2	114.9 (3)	O3—C15—H15A	110.4
C1—C2—C3	122.9 (3)	C16—C15—H15A	110.4
C1—C2—C7	117.8 (3)	O3—C15—H15B	110.4
C3—C2—C7	119.4 (3)	C16—C15—H15B	110.4
C4—C3—C2	120.2 (4)	H15A—C15—H15B	108.6
C4—C3—H3	119.9	C15—C16—H16A	109.5
C2—C3—H3	119.9	C15—C16—H16B	109.5
C3—C4—C5	120.6 (4)	H16A—C16—H16B	109.5
C3—C4—H4	119.7	C15—C16—H16C	109.5
C5—C4—H4	119.7	H16A—C16—H16C	109.5
C6—C5—C4	120.5 (4)	H16B—C16—H16C	109.5
C6—C5—H5	119.7	C22—C17—C18	118.3 (4)
C4—C5—H5	119.7	C22—C17—C11	121.3 (4)
C5—C6—C7	121.1 (4)	C18—C17—C11	120.4 (3)
C5—C6—H6	119.4	C19—C18—C17	120.8 (4)
C7—C6—H6	119.4	C19—C18—H18	119.6
C6—C7—C2	118.1 (4)	C17—C18—H18	119.6
C6—C7—C8	123.1 (4)	C18—C19—C20	119.3 (4)
C2—C7—C8	118.8 (3)	C18—C19—H19	120.4
C9—C8—O4	125.0 (4)	C20—C19—H19	120.4
C9—C8—C7	120.8 (4)	C21—C20—C19	121.2 (4)
O4—C8—C7	114.3 (3)	C21—C20—Br1	119.8 (4)
C8—C9—C10	121.1 (4)	C19—C20—Br1	119.0 (4)
C8—C9—H9	119.5	C20—C21—C22	119.0 (4)
C10—C9—H9	119.5	C20—C21—H21	120.5
C1—C10—C9	118.5 (4)	C22—C21—H21	120.5
C1—C10—C11	121.0 (3)	C17—C22—C21	121.4 (4)
C9—C10—C11	120.4 (3)	C17—C22—H22	119.3
C10—C11—C12	110.1 (3)	C21—C22—H22	119.3
C10—C11—C17	110.4 (3)	O4—C23—H23A	109.5
C12—C11—C17	112.1 (3)	O4—C23—H23B	109.5
C10—C11—H11	108.0	H23A—C23—H23B	109.5
C12—C11—H11	108.0	O4—C23—H23C	109.5
C17—C11—H11	108.0	H23A—C23—H23C	109.5
C13—C12—C14	119.5 (4)	H23B—C23—H23C	109.5
C13—C12—C11	120.6 (3)
C13—O1—C1—C10	−17.1 (5)	C1—C10—C11—C17	−105.9 (4)
C13—O1—C1—C2	162.4 (3)	C9—C10—C11—C17	72.4 (4)
C10—C1—C2—C3	178.4 (3)	C10—C11—C12—C13	−21.7 (5)
O1—C1—C2—C3	−1.0 (5)	C17—C11—C12—C13	101.7 (4)
C10—C1—C2—C7	−1.7 (5)	C10—C11—C12—C14	164.5 (3)
O1—C1—C2—C7	178.8 (3)	C17—C11—C12—C14	−72.1 (4)
C1—C2—C3—C4	−179.5 (4)	C1—O1—C13—N1	−167.7 (3)
C7—C2—C3—C4	0.7 (5)	C1—O1—C13—C12	13.7 (5)
C2—C3—C4—C5	−1.0 (6)	C14—C12—C13—N1	2.2 (6)
C3—C4—C5—C6	0.2 (7)	C11—C12—C13—N1	−171.6 (4)
C4—C5—C6—C7	0.8 (7)	C14—C12—C13—O1	−179.5 (3)
C5—C6—C7—C2	−1.0 (6)	C11—C12—C13—O1	6.8 (5)
C5—C6—C7—C8	179.8 (4)	C15—O3—C14—O2	−3.3 (6)
C1—C2—C7—C6	−179.5 (4)	C15—O3—C14—C12	177.5 (3)
C3—C2—C7—C6	0.3 (5)	C13—C12—C14—O2	10.4 (6)
C1—C2—C7—C8	−0.4 (5)	C11—C12—C14—O2	−175.7 (3)
C3—C2—C7—C8	179.5 (3)	C13—C12—C14—O3	−170.4 (3)
C23—O4—C8—C9	−4.4 (6)	C11—C12—C14—O3	3.4 (5)
C23—O4—C8—C7	174.5 (3)	C14—O3—C15—C16	−166.9 (4)
C6—C7—C8—C9	−178.7 (4)	C10—C11—C17—C22	−111.9 (4)
C2—C7—C8—C9	2.1 (6)	C12—C11—C17—C22	125.0 (4)
C6—C7—C8—O4	2.2 (6)	C10—C11—C17—C18	66.0 (5)
C2—C7—C8—O4	−176.9 (3)	C12—C11—C17—C18	−57.2 (5)
O4—C8—C9—C10	177.0 (3)	C22—C17—C18—C19	0.2 (6)
C7—C8—C9—C10	−1.9 (6)	C11—C17—C18—C19	−177.7 (4)
O1—C1—C10—C9	−178.5 (3)	C17—C18—C19—C20	−0.5 (6)
C2—C1—C10—C9	2.1 (5)	C18—C19—C20—C21	0.4 (7)
O1—C1—C10—C11	−0.2 (5)	C18—C19—C20—Br1	178.9 (3)
C2—C1—C10—C11	−179.6 (3)	C19—C20—C21—C22	0.1 (7)
C8—C9—C10—C1	−0.2 (6)	Br1—C20—C21—C22	−178.4 (3)
C8—C9—C10—C11	−178.5 (4)	C18—C17—C22—C21	0.2 (7)
C1—C10—C11—C12	18.4 (5)	C11—C17—C22—C21	178.1 (4)
C9—C10—C11—C12	−163.3 (3)	C20—C21—C22—C17	−0.4 (7)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H2···O2	0.88 (1)	2.09 (5)	2.744 (5)	131 (5)
N1—H1···O2i	0.88 (1)	2.22 (2)	3.075 (5)	163 (3)
N1—H2···Br1ii	0.88 (4)	2.76 (4)	3.547 (4)	149 (5)
C4—H4···Cg1i	0.93	2.90	3.673 (5)	142
C6—H6···Cg2iii	0.93	2.98	3.743 (5)	140
C23—H23C···Cg3iii	0.96	2.70	3.593 (5)	154

Table 1

Hydrogen-bond geometry (Å, °)

Cg1, Cg2 and Cg3 are the centroids of the C1,C2,C7–C10, C17–C22 and C2–C7 rings, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H2⋯O2	0.88 (1)	2.09 (5)	2.744 (5)	131 (5)
N1—H1⋯O2i	0.88 (1)	2.22 (2)	3.075 (5)	163 (3)
N1—H2⋯Br1ii	0.88 (4)	2.76 (4)	3.547 (4)	149 (5)
C4—H4⋯Cg1i	0.93	2.90	3.673 (5)	142
C6—H6⋯Cg2iii	0.93	2.98	3.743 (5)	140
C23—H23C⋯Cg3iii	0.96	2.70	3.593 (5)	154

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