Startseite The crystal structure of (2R,4S)-5-([1,1′-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)-2-methyl pentanoic acid, C23H29NO4
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The crystal structure of (2R,4S)-5-([1,1′-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)-2-methyl pentanoic acid, C23H29NO4

  • Tingting Han , Shuang Huang , Jing Chen und Yan Zhang EMAIL logo
Veröffentlicht/Copyright: 25. April 2025

Abstract

C23H29NO4, monoclinic, P21 (no. 4), a = 6.8799(3) Å, b = 14.4692(6) Å, c = 11.4832(5) Å, β = 105.680(2)°, V = 1000.57(8) Å3, Z = 2, R gt (F) = 0.0455, wR ref (F 2) = 0.1085, T = 170 K.

CCDC no.: 2424386

The molecular structure is shown in the figure. Table 1 contains the crystallographic data. The list of the atoms including atomic coordinates and displacement parameters can be found in the cif-file attached to this article.

1 Source of materials

Petroleum ether was added dropwise to a vial containing (2R, 4S)-5-([1,1′-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino) -2-methylpentanoic acid (0.38 g, 1 mmol) until saturation was achieved. The vial was sealed with a film, leaving a small pinhole for slow evaporation. After two weeks of storage at room temperature, colorless block crystals were obtained.

Table 1:

Data collection and handling.

Crystal: Colourless block
Size: 0.04 × 0.02 × 0.01 mm
Wavelength: Ga Kα radiation (1.34139 Å)
μ: 0.40 mm−1
Diffractometer, scan mode: Bruker D8 Venture, φ and ω scans
θ max, completeness: 59.4°, 100 %
N(hkl)measured , N(hkl)unique, R int: 20,371, 4,766, 0.051
Criterion for I obs, N(hkl)gt: I obs > 2 σ(I obs), 4,146
N(param)refined: 258
Programs: Bruker, 1 Olex2, 2 SHELX 3 , 4

2 Experimental details

All H atoms were positioned geometrically and refined using a riding model. The O–H, N–H, aromatic C–H, methylene, methine, and methyl H atoms were constrained respectively. Uiso(H) values were set to 1.2 Ueq(C) for CH and CH2 groups, and 1.5 Ueq(C) for CH3 groups.

3 Comment

The title compound, (2R, 4S)-5-([1,1′-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)-2-methylpentanoic acid, serves as a crucial intermediate in the synthesis of an important drug LCZ696. As a dual-acting angiotensin receptor-neprilysin inhibitor, LCZ696 was FDA-approved in 2015 for treating chronic heart failure in patients with reduced ejection fraction, showing significant reductions in cardiovascular mortality and hospitalization rates. 5

While the crystal structure of LCZ696 similar to title compound has been previously reported in the literature, 6 the structural characterization of the title compound remains unreported to date.

The asymmetric unit of the title structure contains one title molecule (cf. left part of the figure), which has two chiral centers at C16 (R configuration) and C14 (S configuration).

Bond lengths and angles are all in the expected ranges in the title molecule. 7

The molecular structure exhibits both intramolecular and intermolecular hydrogen bonding interactions. Three intramolecular hydrogen bonds are observed: C14–H14⋯O4, C21–H21A⋯O3, and C22–H22C⋯O3. Additionally, two intermolecular hydrogen bonds, (N1–H1⋯O1′, ′= 1+x, y, z) and (O2–H2⋯O3″, ″= −1+x, y, z), link adjacent molecules to form an infinite chain propagating along the crystallographic a-axis. (cf. right part of the figure, some hydrogen atoms and the t-butyloxy group are omitted for clarity purpose).


Corresponding author: Yan Zhang, Department of Pharmacy, Nanjing Drum Tower Hospital Group Suqian Hospital, Suqian 223800, Jiangsu Province, People’s Republic of China, E-mail:

  1. Author contribution: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Conflict of interest: The authors declare no conflicts of interest regarding this article.

References

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2. Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A. K.; Puschmann, H. OLEX2: a Complete Structure Solution, Refinement and Analysis Program. J. Appl. Crystallogr. 2009, 42, 339–341; https://doi.org/10.1107/s0021889808042726.Suche in Google Scholar

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7. Shankar, S. P.; Jagodzinska, M.; Malpezzi, L.; Lazzari, P.; Manca, I.; Greig, I. R.; Sani, M.; Zanda, M. Synthesis and Structure–Activity Relationship Studies of Novel Tubulysin U Analogues – Effect on Cytotoxicity of Structural Variations in the Tubuvaline Fragment. Org. Biomol. Chem. 2013, 11, 2273https://doi.org/10.1039/C3OB27111K.Suche in Google Scholar

Received: 2025-02-26
Accepted: 2025-04-02
Published Online: 2025-04-25
Published in Print: 2025-08-26

© 2025 the author(s), published by De Gruyter, Berlin/Boston

This work is licensed under the Creative Commons Attribution 4.0 International License.

Artikel in diesem Heft

  1. Frontmatter
  2. New Crystal Structures
  3. Hydrothermal synthesis, crystal structure of [K3:N1:N2:N4-3-(pyridin-2-yl)-1,2,4-triazole] binuclear Ni(II) complex[Ni2(C7H5N4)2(C7H4ClO2)2]
  4. The crystal structure of di(thiocyanato-κ1N)-bis(methanol)-di(1,3-bis((pyridin-4-ylthio)methyl)benzene)-iron(II), C40H40FeN6O2S6
  5. Crystal structure of poly[(μ 3-3,3″,5,5″-tetrafluoro-(1,1′:4′,1″-terphenyl)-4,4″-dicarboxylate-κ 3 O,O:O″)-(μ 4-3,3″,5,5″-tetrafluoro-(1,1′:4′,1″-terphenyl)-4,4″-dicarboxylate-κ 4 O,O,O,O‴)-dicadmium(II)]dimethylformamide solvate, C47H30Cd2F8N3O12
  6. The crystal structure of a 3d-4f complex based on 2-(benzo[d]thiazol-2-yl)-6-methoxyphenol C31H27N4O13S2CoEr
  7. Crystal structure of poly[(μ 2-1,4-bis(imidazol-1-yl)benzene-k 2 N:N′)(μ 4-biphenyl-3,3′,5,5′-tetracarboxylic-k 4 O,O,O,O)dizinc(II)] dihydrate, C40H28Zn2N8O9
  8. The crystal structure of 4-(bis(2-chloroethyl)amino)-2-hydroxybenzaldehyde, C11H13Cl2NO2
  9. Synthesis and crystal structure of-(10S,13S,16R,Z) −17-ethylidene-16-hydroxy-10,13-dimethylhexadecahydro-3 H-cyclopenta[α]phenanthren-3-one, C21H32O2
  10. The crystal structure of catena-((μ 2-4,4′-bipyridine-κ 2 N:N′)-bis(4-fluorobenzoato-κ1O)-copper(II)), C24H16F2N2O4Cu
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  12. The crystal structure of 4-chloro-1H-pyrazole-3-carboxylic acid, C4H3ClN2O2
  13. The crystal structure of bepotastine besilate, C27H31ClN2O6S
  14. The crystal structure of (η 6-p-cymene)benzyldiphenylphosphine-diiodido-ruthenium(II) dichloromethane solvate
  15. The crystal structure of poly[(μ 2-1-(1-imidazolyl)-4- (imidazol-1′-yl-methyl)benzene κ 2 N:N′)-(μ 2-3-nitrobenzene -1,2-dicarboxylato-k4,O,O′:O′′,O′′′]zinc(II)-κ 2, C21H15N5O6Zn
  16. The crystal structure of (2R,4S)-5-([1,1′-biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)-2-methyl pentanoic acid, C23H29NO4
  17. The crystal strucure of [2,2′-{1,2-phenylenebis [(azanylylidene)methanylylidene]}bis(4-fluorophenolato)-κ4 N,N′,O,O′] nickel(II) N, N-dimethylformamide solvate, C23H19F2N3NiO3
  18. The structure of (E)-6-(cyclopropylmethyl)-11-(2,2-difluoropropylidene)-2-methyl-6, 11-dihydrodibenzo[c,f][1,2]thiazepine 5,5-dioxide, C21H21F2NO2S
  19. Crystal structure of catena-poly[(μ 2-(2-(1H-imidazol-1-ylmethyl)benzyl)-1H-imidazole κ2N:N′)- (μ 2-cyclohexane-1,2-dicarboxylato κ2O,O′)cobalt(II) monohydrate]
  20. The crystal structure of 3,5,7-trinitro-1,3,5,7-oxatriazocane
  21. Crystal structure of poly[(μ2-nitrato-κ3 O,O′:O′′)(μ2-1-[(2-propyl-1H-benzimidazole-1-yl)methyl]-1H-benzotriazole-k2 N:N′)silver(I)], C17H17AgN6O3
  22. The crystal structure of (5-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-sulfanylidene-1,3,4-oxadiazol-3(2H)-yl)(3-methylphenyl)methanone, C18H14N2O4S
  23. The crystal structure of diaqua-bis[5-(4-methylphenyl)-1H-pyrazole-3-carboxylato-κ2N,O]-cobalt(II), C11H11Co0.5N2O3
  24. Crystal structure of 2-(6-methoxynaphthalen-2-yl)-N-(4-morpholinophenyl)propanamide, C24H26N2O3
  25. The crystal structure of sodium methylsulfonate
  26. Crystal structure of catena-poly[bis(isothiocyanate κ 1 N)-(μ 2-3,3ʹ-methylenebis(1-methyl-1,3-dihydro-2H-imidazole-2-thione)-κ 2 S:S′)-cobalt(II)], C11H12CoN6S4
  27. The crystal structure of {hexakis(1-methyl-1H-imidazole-κ 1N)nickel(II)} (μ 2-oxo)-hexaoxido-di-molybdenum(VI)─1-methyl-1H-imidazole (1/2), C32H48NiMo2N16O7
  28. 6-(Diphenylphosphoryl)-3,3′,6′-tris(10H-phenoxazin-10-yl)-[1,1′-biphenyl]-2,2′-dicarbonitrile, C62H38N5O4P
  29. The crystal structure of R-2′-amino-N-methyl-N-(1-phenylethyl)-[1,1′-biphenyl]-4-carboxamide, C22H22N2O
  30. The crystal structure of bis{tetrakis(n-butyl)(μ-hydroxy)(2,3,5,6-tetrafluorobenzoate) (μ 3 -oxo)ditin(IV)}
  31. Crystal structure of catena-poly[aqua-(μ 2(3,4-dimethylthieno[2,3-b]thiophene-2,5-dicarboxylato-κ 2 O:O′)-(3,6-bis(4′-pyridyl)-1,2,4,5-tetrazine-κ 1 N)zinc(II)], C22H16N6O5S2Zn
  32. The crystal structure of 3-bromo-5-cyano–N-(5-(cyanomethyl)quinolin-8-yl)pentanamide, C19H15BrN4O
  33. The crystal structure of bis(tetramethylammonium) (di-μ2-aqua)hexaaqua-dibarium(II)) decavanadate
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  37. The crystal structure of 2-acetylpyridine-ortho-fluoro-phenylhydrazone, C14H12FN3O
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  50. Crystal structure of-(1S,4aR,5S)-5,6,7-trihydroxy-8-isopropyl-1-methyl-1,2,3,4,5,10,11,11a-octahydro-4a,1-(epoxymethano)dibenzo[a,d][7]annulen-13-one C20H26O5
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  53. Crystal structure of N-(adamantan-1-yl)-4-methylpiperazine-1-carbothioamide, C16H27N3S
  54. Crystal structure of poly[(μ 2-2,2′-[1,4-phenylenebis(methylenesulfanediyl)]dibenzoato-κ 4 O,O′:O″,O‴)-(μ 2-1,1′-([1,1′-biphenyl]-4,4′-diyl)bis(1H-benzimidazole)-κ 2 N:N′)cadmium(II)]dimethylformamide solvate, C51H41N5O5S2Cd
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  56. The crystal structure of 1-(4-cyanobenzyl)-4-phenyl-1,4-dihydropyridine-3-carbonitrile, C20H15N3
  57. Crystal structure of (1,3-dioxolan-2-ylmethyl)triphenylphosphonium bromide, C22H22BrO2P
  58. Crystal structure of [(2,4-dichlorobenzyl)triphenylphosphonium] tetrachloridomanganese(II)
  59. The crystal structure of 2-(2-hydroxy-4-n-octyloxyphenyl)-4,6-bis(2,4-dimethylphenyl)-1,3,5-triazine, C33H39N3O2
  60. Crystal structure of catena-poly[aqua-(5-carboxypyridine-2-carboxylate-κ 2N,O)(2,5-pyridine-dicarboxylate-κ 4O,O′:N:O″)bismuth(III)], C14H9BiN2O9
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