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Acta Crystallographica Section E: Structure Reports Online logoLink to Acta Crystallographica Section E: Structure Reports Online
. 2009 Dec 9;66(Pt 1):o87–o88. doi: 10.1107/S1600536809052258

2-[2-(4-Methoxyphenyl)-2,3-dihydro-1H-1,5-benzodiazepin-4-yl]phenol

Yvon Bibila Mayaya Bisseyou a,*, Ané Adjou b, Yapi Marcellin Yapo a, Guy Euloge Bany a, R C A Kakou-Yao a
PMCID: PMC2980025  PMID: 21580184

Abstract

In the structure of title compound, C22H20O2N2, the 11-membered benzodiazepine ring system adopts a distorted boat conformation. The benzene ring of this system forms dihedral angles of 89.69 (12) and 48.82 (12)° with those of the phenol and methoxy­phenyl substituents, respectively. The dihedral angle between the benzene rings is 49.61 (11)°. An intra­molecular O—H⋯N hydrogen bond generates an S(6) ring.

Related literature

For the biological activity of heterocyclic scaffolds containing nitro­gen atoms, see: MacDonald (2002 ▶); Gringauz (1999 ▶); Albright et al. (1998 ▶); Rahbaek et al. (1999 ▶). For related structures, see: Ravichandran et al. (2009a ▶,b ▶,c ▶,d ▶). For puckering parameters, see: Cremer & Pople (1975 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). For the weighting scheme, see: Prince (1982 ▶); Watkin (1994 ▶).graphic file with name e-66-00o87-scheme1.jpg

Experimental

Crystal data

  • C22H20N2O2

  • M r = 344.41

  • Monoclinic, Inline graphic

  • a = 27.5064 (5) Å

  • b = 7.3811 (2) Å

  • c = 19.5038 (4) Å

  • β = 117.699 (2)°

  • V = 3506.02 (15) Å3

  • Z = 8

  • Mo Kα radiation

  • μ = 0.08 mm−1

  • T = 223 K

  • 0.30 × 0.20 × 0.15 mm

Data collection

  • Nonius KappaCCD diffractometer

  • 19187 measured reflections

  • 2507 independent reflections

  • 2836 reflections with I > 3σ(I)

  • R int = 0.06

Refinement

  • R[F 2 > 2σ(F 2)] = 0.055

  • wR(F 2) = 0.065

  • S = 1.04

  • 2507 reflections

  • 235 parameters

  • H-atom parameters constrained

  • Δρmax = 0.25 e Å−3

  • Δρmin = −0.25 e Å−3

Data collection: COLLECT (Nonius, 2001 ▶); cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997 ▶); data reduction: DENZO/SCALEPACK; program(s) used to solve structure: SIR92 (Altomare et al., 1994 ▶); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: CRYSTALS.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809052258/bq2181sup1.cif

e-66-00o87-sup1.cif (17.8KB, cif)

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809052258/bq2181Isup2.hkl

e-66-00o87-Isup2.hkl (225.3KB, hkl)

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A D—H H⋯A D⋯A D—H⋯A
O1—H11⋯N1 0.87 1.74 2.523 (3) 148
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Acknowledgments

The authors thank the Spectropôle Service of the Faculty of Sciences and Techniques of Saint Jérôme (France) for the use of the diffractometer.

supplementary crystallographic information

Comment

Heterocyclic scaffolds containing nitrogen atoms have received great attention in organic and medicinal chemistry because of their broad range of beneficial biological properties. These heterocyclic compounds such as benzodiazepines exhibit bioactive profile including anticonvulsant (MacDonald, 2002), hypnotic (Gringauz, 1999) and vasopressin antagonists (Albright et al., 1998) activities. They are also used for treatment of gastrointestinal and central nervous system (CNS) disorder (Rahbaek et al., 1999). As part of continuing work on heterocyclic compounds biologically active, we have synthesized new benzodiazepine derivative in order to explore the effects of substituents on activity and scaffold conformation of this compound class. In this paper, we present molecular structure of the title compound. The molecular structure of title compound is shown in Fig. 1. The benzodiazepine ring system adopts a distorted boat conformation as shown in the recent studies related to benzodiazepine derivatives (Ravichandran et al., 2009a,b,c,d). The puckering parameters (Cremer & Pople, 1975) for this eleven-membered benzodiazepine ring system are: Q2 = 1.087 (3) Å,Q3 = 0.654 (3) Å,φ2 = 320.74 (4)° and φ3 = 26.7 (2)°. The benzene ring of this system forms dihedral angles of 89.69 (12)° and 48.82 (12)° with the phenyl rings of phenol and methoxy-phenyl fragments respectively which make them dihedral angle of 49.61 (11)°. Furthermore, there is in this structure the presence of O—H···N intra-molecular hydrogen bond, which generates an S (6) graph set motif (Bernstein et al., 1995).

Experimental

To a solution of 1-(2-hydroxyphenyl)-3-(p-tolyl) propenone (1.3 g, 5.4 mmol) and 1, 2-diaminobenzene in anhydrous ethanol (20 ml), was added triethylamine (6 ml, 32.4 mmol). The reaction mixture was stirred under shelter from the light for 24 h. The resulting mixture was cooled at room temperature then kept in the freezer all night long. The precipitate was then filtered and purified by chromatography silica gel. Elution solvent: hexane/ethyl acetate (90/10). We obtained yellow single crystals of title compound with a yield of 56% (m.p.: 413–415 K; Rf: 1/2, hexane/ethyl acetate: 80/20).

Refinement

The H atoms were all located in a difference of Fourier map. They were all initially refined with soft restraints on the bond lengths and angles to regularize their geometry (C—H in the range 0.95–0.97 Å, O—H = 0.87 Å, N—H = 0.88 Å and Uiso(H)in the range 1.2–1.7 times Ueq of the parent atom), after which their positions were refined with riding constraints.

Figures

Fig. 1.

Fig. 1.

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The molecular structure of the title compound and the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. Dashed lines indicate hydrogen bonds.

Crystal data

C22H20N2O2 F(000) = 1456
Mr = 344.41 Dx = 1.305 Mg m−3
Monoclinic, C2/c Melting point = 413–415 K
Hall symbol: -C 2yc Mo Kα radiation, λ = 0.71073 Å
a = 27.5064 (5) Å Cell parameters from 19187 reflections
b = 7.3811 (2) Å θ = 0–0°
c = 19.5038 (4) Å µ = 0.08 mm−1
β = 117.699 (2)° T = 223 K
V = 3506.02 (15) Å3 Block, yellow
Z = 8 0.30 × 0.20 × 0.15 mm
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Data collection

Nonius KappaCCD diffractometer Rint = 0.06
graphite θmax = 29.1°, θmin = 1.7°
φ and ω scans h = −37→32
19187 measured reflections k = −10→10
2507 independent reflections l = −25→25
2836 reflections with I > 3σ(I)
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Refinement

Refinement on F2 Primary atom site location: structure-invariant direct methods
Least-squares matrix: full Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.055 H-atom parameters constrained
wR(F2) = 0.065 Method, part 1, Chebychev polynomial, (Watkin, 1994, Prince, 1982) [weight] = 1.0/[A0*T0(x) + A1*T1(x) ··· + An-1]*Tn-1(x)] where Ai are the Chebychev coefficients listed below and x = F /Fmax Method = Robust Weighting (Prince, 1982) W = [weight] * [1-(deltaF/6*sigmaF)2]2 Ai are: 76.3 80.0 28.8 -10.0 -11.5
S = 1.04 (Δ/σ)max = 0.0004
2507 reflections Δρmax = 0.25 e Å−3
235 parameters Δρmin = −0.25 e Å−3
0 restraints
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Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

x y z Uiso*/Ueq
O1 0.93812 (7) 0.1834 (2) 0.28604 (9) 0.0613
O2 0.74005 (6) 0.9744 (2) 0.19252 (11) 0.0715
N1 0.92187 (7) 0.2773 (2) 0.15267 (10) 0.0441
N2 0.82826 (7) 0.4219 (3) 0.02002 (10) 0.0518
C1 0.90766 (9) 0.2197 (3) 0.07668 (13) 0.0465
C2 0.86133 (9) 0.2877 (3) 0.01157 (13) 0.0481
C3 0.84587 (10) 0.2063 (4) −0.06017 (14) 0.0600
C4 0.87638 (12) 0.0637 (4) −0.06710 (17) 0.0694
C5 0.92265 (12) 0.0009 (4) −0.00312 (18) 0.0690
C6 0.93752 (10) 0.0773 (3) 0.06788 (16) 0.0572
C7 0.92184 (7) 0.4477 (3) 0.16870 (12) 0.0385
C8 0.91134 (8) 0.5878 (3) 0.10725 (12) 0.0404
C9 0.85020 (8) 0.6032 (3) 0.04950 (12) 0.0435
C10 0.81802 (8) 0.6940 (3) 0.08532 (11) 0.0405
C11 0.82500 (9) 0.8789 (3) 0.10081 (14) 0.0547
C12 0.79940 (9) 0.9683 (3) 0.13693 (15) 0.0584
C13 0.76448 (8) 0.8738 (3) 0.15756 (14) 0.0526
C14 0.75569 (9) 0.6925 (3) 0.14123 (13) 0.0509
C15 0.78302 (8) 0.6032 (3) 0.10597 (12) 0.0475
C16 0.93285 (8) 0.4968 (3) 0.24729 (12) 0.0384
C17 0.93531 (8) 0.6780 (3) 0.27066 (12) 0.0442
C18 0.94419 (8) 0.7245 (3) 0.34386 (13) 0.0506
C19 0.95159 (9) 0.5901 (3) 0.39714 (13) 0.0532
C20 0.95014 (9) 0.4115 (3) 0.37696 (13) 0.0532
C21 0.94043 (8) 0.3622 (3) 0.30257 (13) 0.0455
C22 0.69528 (10) 0.8907 (4) 0.19955 (17) 0.0766
H82 0.9309 0.5495 0.0775 0.0489*
H81 0.9244 0.7079 0.1309 0.0491*
H191 0.9568 0.6222 0.4495 0.0668*
H91 0.8471 0.6809 0.0055 0.0540*
H111 0.8489 0.9442 0.0849 0.0673*
H141 0.7308 0.6258 0.1547 0.0624*
H151 0.7763 0.4730 0.0942 0.0604*
H201 0.9565 0.3167 0.4133 0.0656*
H51 0.9445 −0.0943 −0.0083 0.0953*
H171 0.9305 0.7735 0.2334 0.0558*
H181 0.9460 0.8507 0.3583 0.0644*
H21 0.7927 0.4133 −0.0098 0.0665*
H41 0.8660 0.0108 −0.1167 0.0911*
H121 0.8062 1.0951 0.1497 0.0723*
H31 0.8135 0.2496 −0.1043 0.0789*
H61 0.9693 0.0325 0.1134 0.0794*
H222 0.6805 0.9858 0.2210 0.1264*
H223 0.6683 0.8514 0.1473 0.1269*
H221 0.7094 0.7849 0.2350 0.1273*
H11 0.9322 0.1725 0.2385 0.0949*
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Atomic displacement parameters (Å2)

U11 U22 U33 U12 U13 U23
O1 0.0752 (11) 0.0399 (10) 0.0615 (10) 0.0001 (8) 0.0257 (9) 0.0135 (8)
O2 0.0518 (10) 0.0654 (12) 0.1058 (14) −0.0043 (9) 0.0437 (10) −0.0231 (10)
N1 0.0415 (10) 0.0383 (10) 0.0543 (11) −0.0021 (8) 0.0238 (9) 0.0006 (8)
N2 0.0363 (9) 0.0547 (12) 0.0585 (12) −0.0069 (9) 0.0171 (9) −0.0094 (10)
C1 0.0465 (12) 0.0374 (12) 0.0636 (15) −0.0115 (10) 0.0324 (12) −0.0060 (11)
C2 0.0481 (13) 0.0476 (13) 0.0560 (14) −0.0169 (11) 0.0305 (11) −0.0092 (11)
C3 0.0607 (15) 0.0623 (16) 0.0641 (16) −0.0240 (13) 0.0348 (13) −0.0153 (13)
C4 0.0840 (19) 0.0658 (18) 0.0814 (19) −0.0386 (16) 0.0579 (17) −0.0348 (16)
C5 0.0725 (18) 0.0542 (16) 0.100 (2) −0.0212 (14) 0.0570 (18) −0.0257 (16)
C6 0.0564 (13) 0.0436 (13) 0.0811 (17) −0.0112 (12) 0.0401 (13) −0.0116 (13)
C7 0.0296 (10) 0.0354 (11) 0.0507 (12) −0.0019 (8) 0.0187 (9) 0.0036 (9)
C8 0.0369 (10) 0.0366 (11) 0.0494 (12) −0.0043 (9) 0.0216 (9) 0.0028 (10)
C9 0.0388 (11) 0.0449 (13) 0.0442 (12) −0.0031 (10) 0.0171 (9) 0.0070 (10)
C10 0.0321 (10) 0.0391 (12) 0.0441 (12) −0.0001 (9) 0.0123 (9) 0.0076 (9)
C11 0.0426 (12) 0.0419 (14) 0.0816 (17) −0.0022 (10) 0.0307 (12) 0.0095 (12)
C12 0.0417 (12) 0.0384 (13) 0.0939 (19) −0.0027 (10) 0.0305 (13) −0.0044 (13)
C13 0.0370 (12) 0.0511 (14) 0.0664 (15) 0.0017 (11) 0.0211 (11) −0.0061 (12)
C14 0.0436 (12) 0.0480 (14) 0.0668 (15) −0.0064 (11) 0.0304 (11) −0.0008 (12)
C15 0.0457 (12) 0.0391 (12) 0.0596 (14) −0.0059 (10) 0.0262 (11) 0.0006 (11)
C16 0.0296 (10) 0.0379 (11) 0.0459 (12) 0.0015 (8) 0.0161 (9) 0.0061 (9)
C17 0.0392 (11) 0.0400 (13) 0.0526 (13) 0.0036 (9) 0.0206 (10) 0.0063 (10)
C18 0.0472 (13) 0.0501 (13) 0.0550 (14) 0.0061 (11) 0.0242 (11) −0.0012 (11)
C19 0.0447 (12) 0.0661 (16) 0.0488 (13) 0.0071 (12) 0.0217 (11) 0.0046 (12)
C20 0.0476 (13) 0.0612 (15) 0.0501 (13) 0.0048 (12) 0.0221 (11) 0.0162 (12)
C21 0.0369 (11) 0.0418 (12) 0.0544 (13) 0.0019 (10) 0.0182 (10) 0.0107 (11)
C22 0.0595 (15) 0.087 (2) 0.097 (2) −0.0058 (16) 0.0485 (16) −0.0176 (18)
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Geometric parameters (Å, °)

O1—C21 1.353 (2) C9—H91 1.002
O1—H11 0.867 C10—C11 1.392 (3)
O2—C13 1.376 (3) C10—C15 1.378 (3)
O2—C22 1.440 (3) C11—C12 1.374 (3)
N1—C1 1.411 (3) C11—H111 0.975
N1—C7 1.297 (3) C12—C13 1.389 (3)
N2—C2 1.405 (3) C12—H121 0.964
N2—C9 1.470 (3) C13—C14 1.371 (3)
N2—H21 0.877 C14—C15 1.397 (3)
C1—C2 1.409 (3) C14—H141 0.972
C1—C6 1.393 (3) C15—H151 0.986
C2—C3 1.395 (3) C16—C17 1.405 (3)
C3—C4 1.391 (3) C16—C21 1.409 (3)
C3—H31 0.960 C17—C18 1.375 (3)
C4—C5 1.384 (4) C17—H171 0.976
C4—H41 0.956 C18—C19 1.381 (3)
C5—C6 1.370 (3) C18—H181 0.968
C5—H51 0.960 C19—C20 1.371 (3)
C6—H61 0.970 C19—H191 0.993
C7—C8 1.505 (3) C20—C21 1.396 (3)
C7—C16 1.463 (3) C20—H201 0.953
C8—C9 1.533 (3) C22—H222 0.997
C8—H82 0.999 C22—H223 0.985
C8—H81 0.987 C22—H221 0.995
C9—C10 1.515 (3)
C21—O1—H11 108.1 C11—C10—C15 117.3 (2)
C13—O2—C22 116.84 (19) C10—C11—C12 122.0 (2)
C1—N1—C7 120.97 (18) C10—C11—H111 117.5
C2—N2—C9 121.12 (16) C12—C11—H111 120.5
C2—N2—H21 117.0 C11—C12—C13 119.7 (2)
C9—N2—H21 117.0 C11—C12—H121 120.9
N1—C1—C2 122.16 (19) C13—C12—H121 119.3
N1—C1—C6 117.7 (2) C12—C13—O2 115.8 (2)
C2—C1—C6 119.7 (2) C12—C13—C14 119.6 (2)
C1—C2—N2 120.6 (2) O2—C13—C14 124.6 (2)
C1—C2—C3 118.5 (2) C13—C14—C15 119.8 (2)
N2—C2—C3 120.6 (2) C13—C14—H141 120.1
C2—C3—C4 120.4 (3) C15—C14—H141 120.1
C2—C3—H31 118.6 C14—C15—C10 121.6 (2)
C4—C3—H31 120.9 C14—C15—H151 119.3
C3—C4—C5 120.6 (2) C10—C15—H151 119.2
C3—C4—H41 119.9 C7—C16—C17 122.07 (19)
C5—C4—H41 119.5 C7—C16—C21 120.80 (19)
C4—C5—C6 119.4 (3) C17—C16—C21 117.1 (2)
C4—C5—H51 120.6 C16—C17—C18 122.2 (2)
C6—C5—H51 120.0 C16—C17—H171 118.5
C1—C6—C5 121.3 (3) C18—C17—H171 119.4
C1—C6—H61 118.5 C17—C18—C19 119.7 (2)
C5—C6—H61 120.2 C17—C18—H181 120.2
N1—C7—C8 119.71 (19) C19—C18—H181 120.2
N1—C7—C16 118.03 (19) C18—C19—C20 120.0 (2)
C8—C7—C16 122.26 (18) C18—C19—H191 120.2
C7—C8—C9 112.03 (16) C20—C19—H191 119.7
C7—C8—H82 108.3 C19—C20—C21 121.0 (2)
C9—C8—H82 107.3 C19—C20—H201 121.4
C7—C8—H81 110.6 C21—C20—H201 117.5
C9—C8—H81 108.3 C16—C21—C20 120.0 (2)
H82—C8—H81 110.3 C16—C21—O1 122.1 (2)
C8—C9—N2 109.30 (17) C20—C21—O1 117.9 (2)
C8—C9—C10 111.76 (17) O2—C22—H222 105.8
N2—C9—C10 111.18 (16) O2—C22—H223 107.2
C8—C9—H91 107.4 H222—C22—H223 112.5
N2—C9—H91 109.2 O2—C22—H221 109.1
C10—C9—H91 107.8 H222—C22—H221 111.4
C9—C10—C11 118.86 (19) H223—C22—H221 110.6
C9—C10—C15 123.85 (19)
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Hydrogen-bond geometry (Å, °)

D—H···A D—H H···A D···A D—H···A
O1—H11···N1 0.87 1.74 2.523 (3) 148
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Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BQ2181).

References

  1. Albright, J. D., Feich, M. F., Santos, E. G. D., Dusza, J. P., Sum, F.-W., Venkatesan, A. M., Coupet, J., Chan, P. S., Ru, X., Mazandarani, H. & Bailey, T. (1998). J. Med. Chem.41, 2442–2444. [DOI] [PubMed]
  2. Altomare, A., Cascarano, G., Giacovazzo, C., Guagliardi, A., Burla, M. C., Polidori, G. & Camalli, M. (1994). J. Appl. Cryst.27, 435.
  3. Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl.34, 1555–1573.
  4. Betteridge, P. W., Carruthers, J. R., Cooper, R. I., Prout, K. & Watkin, D. J. (2003). J. Appl. Cryst.36, 1487.
  5. Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc.97, 1354–1358.
  6. Farrugia, L. J. (1997). J. Appl. Cryst.30, 565.
  7. Gringauz, A. (1999). Introduction to Medicinal Chemistry, pp. 578–580. New York: Wiley-VCH.
  8. MacDonald, R. L. (2002). Benzodiazepines - Mechanisms of Action In Antiepileptic Drugs, 5th ed., edited by R. H. Levy, R. H. Mattson, B. S. Meldrum & E. Perucca, pp. 179–186. Philadelphia: Lippincott Williams and Wilkins.
  9. Nonius (2001). COLLECT Nonius BV, Delft, The Netherlands.
  10. Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307–326. New York: Academic Press.
  11. Prince, E. (1982). Mathematical Techniques in Crystallography and Materials Science New York: Springer-Verlag.
  12. Rahbaek, L., Breinholt, J., Frisvad, J. C. & Christophersen, C. (1999). J. Org. Chem.64, 1689–1692. [DOI] [PubMed]
  13. Ravichandran, K., Sakthivel, P., Ponnuswamy, S., Ramesh, P. & Ponnuswamy, M. N. (2009a). Acta Cryst. E65, o2361. [DOI] [PMC free article] [PubMed]
  14. Ravichandran, K., Sakthivel, P., Ponnuswamy, S., Ramesh, P. & Ponnuswamy, M. N. (2009b). Acta Cryst. E65, o2362. [DOI] [PMC free article] [PubMed]
  15. Ravichandran, K., Sakthivel, P., Ponnuswamy, S., Shalini, M. & Ponnuswamy, M. N. (2009c). Acta Cryst. E65, o2551–o2552. [DOI] [PMC free article] [PubMed]
  16. Ravichandran, K., Sathiyaraj, K., Ilango, S. S., Ponnuswamy, S. & Ponnuswamy, M. N. (2009d). Acta Cryst. E65, o2363–o2364. [DOI] [PMC free article] [PubMed]
  17. Watkin, D. (1994). Acta Cryst. A50, 411–437.

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809052258/bq2181sup1.cif

e-66-00o87-sup1.cif (17.8KB, cif)

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809052258/bq2181Isup2.hkl

e-66-00o87-Isup2.hkl (225.3KB, hkl)

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

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography

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