research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 82| Part 6| June 2026| Pages 651-655
https://doi.org/10.1107/S2056989026004482

Avutometinib

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Jacob K. Salazar,a James A. Kaduk,b,c* Anja Dosend and Thomas N. Blantond

aNorth Central College, Department of Chemistry, 131 S. Loomis St., Naperville IL 60540 , USA, bNorth Central College, Department of Physics, 131 S. Loomis St., Naperville IL 60540 , USA, cIllinois Institute of Technology, Department of Chemistry, 3101 S. Dearborn St., Chicago IL 60616, USA, and dICDD, 12 Campus Blvd., Newtown Square PA 19073-3273, USA
*Correspondence e-mail: [email protected]

Edited by F. F. Ferreira, Universidade Federal do ABC, Brazil (Received 20 April 2026; accepted 28 April 2026; online 15 May 2026)

The crystal structure of avutometinib (systematic name: 3-{[3-fluoro-2-(methyl­sulfamoyl­amino)­pyridin-4-yl]meth­yl}-4-methyl-7-(pyrimidin-2-yloxy)­chro­men-2-one), C21H18FN5O5S, has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional theory techniques. Avutometinib crystallizes in space group P1 (#2). The crystal structure is composed of layers parallel to the ab plane. N—H⋯O hydrogen bonds link the layers along the a-axis direction. The mol­ecule is Z-shaped.

CCDC references: 2551067; 2551068

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1. Chemical context

Avutometinib (AVNAPKI) has been approved as a treatment for ovarian cancer. AVNAPKI is administered in capsule form as a co-medication with FAKZYNJA™ (defactinib tablets), for the treatment of KRAS-mutated recurrent low-grade serous ovarian cancer for patients that have previously received unsuccessful systemic therapy. The systematic name (CAS Registry Number 946128-88-7) is 3-{[3-fluoro-2-(methyl­sulfamoyl­amino)-4-pyridin­yl]meth­yl}-4-methyl-7-pyrimidin-2-yloxychromen-2-one.

We are unaware of any published powder diffraction data for avutometinib. This work was carried out as part of a project (Kaduk et al., 2014View full citation) to determine the crystal structures of large-volume commercial pharmaceuticals, and include high-quality powder diffraction data for them in the Powder Diffraction File (Kabekkodu et al., 2024View full citation).

[Scheme 1]

2. Structural commentary

The root-mean-square difference of the non-H atoms in the Rietveld-refined and VASP-optimized structures of avutometinib, calculated using the Mercury (Macrae et al., 2020View full citation) CSD-Materials/Search/Crystal Packing Similarity tool is 0.059 Å (Fig. 1[link]); the structures are essentially identical. The root-mean-square Cartesian displacement of the non-H atoms in the refined and optimized structures, calculated using the Mercury Calculate/Mol­ecule Overlay tool, is 0.053 Å (Fig. 2[link]). The agreements are within the normal range for correct structures (van de Streek & Neumann, 2014View full citation). The asymmetric unit is illustrated in Fig. 3[link]. The remaining discussion will emphasize the VASP-optimized structure.

[Figure 1]
Figure 1
Comparison of the Rietveld-refined (colored by atom type) and VASP-optimized (pale green) structures of avutometinib, calculated using the Mercury CSD-Materials/Search/Crystal Packing Similarity tool. The root-mean-square Cartesian displacement is 0.059 Å. Image generated using Mercury (Macrae et al., 2020View full citation).
[Figure 2]
Figure 2
Comparison of the refined structure of avutometinib (red) to the VASP-optimized structure (blue). The comparison was generated using the Mercury Calculate/Mol­ecule Overlay tool; the r.m.s. difference is 0.053 Å. Image generated using Mercury (Macrae et al., 2020View full citation).
[Figure 3]
Figure 3
The asymmetric unit of avutometinib, with the atom numbering. The atoms are represented by 50% probability spheroids. Image generated using Mercury (Macrae et al., 2020View full citation).

All of the bond distances, bond angles, and torsion angles fall within the normal ranges indicated by a Mercury Mogul Geometry check (Macrae et al., 2020View full citation). Only the S1—N8 bond of 1.682 Å [average = 1.628 (17); Z-score = 3.1] is flagged as unusual. The unusual S—N bond distance is an example of a known feature of DFT calculations: too-long S—N bonds in the DFT optimization of sulfonamides have been observed (Kaduk et al., 2025View full citation; Vibha et al., 2023View full citation; Whitfield, 2025View full citation).

Quantum chemical geometry optimization of the isolated avutometinib mol­ecule (DFT/B3LYP/6-31G*/water) using Spartan '24 (Wavefunction, 2025View full citation) indicated that the observed conformation is 5.7 kcal mol−1 higher in energy than a local minimum, which has a very similar conformation. The global minimum-energy conformation is 79.9 kcal mol−1 lower in energy, but is folded on itself to make intra­molecular hydrogen bonds. Inter­molecular inter­actions are thus important in determining the observed solid-state conformation.

3. Supra­molecular features

The crystal structure (Fig. 4[link]) is composed of layers lying parallel to the ab plane. Hydrogen bonds link the layers along the b-axis direction (Table 1[link]). The mol­ecule is Z-shaped. The mean plane of the pyridine ring near the sulfonamide group is approximately (011), the mean plane of the 2H-chromen-2-one ring system is approximately (01Mathematical equation), and the mean plane of the pyrimidine ring is approximately (123). The Mercury Aromatics Analyser indicates one strong inter­action (d = 4.334 Å) between phenyl rings of the 2H-chromen-2-one ring system, and weaker inter­actions between multiple pairs of rings.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A Mulliken overlap H-bond energy
N8—H44⋯O4i 1.04 1.95 2.961 165 0.054 5.4
N10—H45⋯O7ii 1.03 2.22 3.223 163 0.026 3.7
N10—H45⋯N9 1.03 2.49 2.977 108 0.011 –
C24—H41⋯O6iii 1.09 2.42 3.183 126 0.011 –
C33—H51⋯O6iv 1.09 2.35 3.170 131 0.015 –
C21—H39⋯N11i 1.09 2.80 3.882 170 0.012 –
C31—H49⋯N10iv 1.09 2.82 3.777 145 0.011 –
Symmetry codes: (i) x − 1, y, z; (ii) −x, −y, 1 − z; (iii) x + 1, y, z; (iv) x + 2, y, z − 1.
[Figure 4]
Figure 4
Crystal structure of avutometinib, viewed down the a-axis. Image generated using DIAMOND (Brandenburg & Putz, 2025View full citation).

Analysis of the contributions to the total crystal energy of the structure using the Forcite module of Materials Studio (Dassault Systèmes, 2024View full citation) indicated that the intra­molecular energy is dominated by angle distortion terms, as might be expected for a mol­ecule containing a fused ring system. The inter­molecular energy is dominated by van der Waals attractions, which in this force field based analysis include hydrogen bonds. The hydrogen bonds are better discussed using the results of the DFT calculation.

There are two classical N—H⋯O hydrogen bonds in the structure (Table 1[link]), one intra­molecular and one inter­molecular. The energies of these hydrogen bonds were calculated using the correlation of Wheatley and Kaduk (2019View full citation). The inter­molecular N8—H44⋯O4 hydrogen bonds link the mol­ecules into chains along the a-axis direction, with graph set C11(9) (Etter, 1990View full citation; Bernstein et al., 1995View full citation; Motherwell et al., 2000View full citation). A few C—H⋯O and C—H⋯N hydrogen bonds also contribute to the cohesion of the crystal.

The volume enclosed by the Hirshfeld surface of avutometinib (Fig. 5[link], Hirshfeld, 1977View full citation; Spackman et al., 2021View full citation) is 498.97 Å3, 98.27% of half of the unit-cell volume. The packing density is thus typical. The only significant close contacts (red in Fig. 5[link]) involve the hydrogen bonds. The volume/non-hydrogen atom is smaller than normal, at 15.4 Å3.

[Figure 5]
Figure 5
The Hirshfeld surface of avutometinib. Inter­molecular contacts longer than the sums of the van der Waals radii are colored blue, and contacts shorter than the sums of the radii are colored red. Contacts equal to the sums of radii are white. Image generated using CrystalExplorer (Spackman et al., 2021View full citation).

The Bravais–Friedel–Donnay–Harker (Bravais, 1866View full citation; Friedel, 1907View full citation; Donnay and Harker, 1937View full citation) algorithm suggests that we might expect lozenge morphology for avutometinib, with {001} as the major faces. A 2nd-order spherical harmonic model for preferred orientation was included. The texture index was 1.002, indicating that the preferred orientation was insignificant in this rotated capillary specimen.

4. Database survey

A reduced cell search of the Cambridge Structural Database (Groom et al., 2016View full citation) yielded no hits.

5. Synthesis and crystallization

Avutometinib was a commercial reagent, purchased from Sigma (Batch #A245684-HA3), and was used as-received.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. The white powder was packed into a 1.5 mm diameter Kapton capillary, and rotated during the measurement at ∼50 Hz. The powder pattern was measured at 295 K at beam line 11-BM (Lee et al., 2008View full citation; Wang et al., 2008View full citation; Antao et al., 2008View full citation) of the Advanced Photon Source at Argonne National Laboratory using a wavelength of 0.4687342 Å from 0.5–50° 2θ with a step size of 0.001° and a counting time of 0.1 sec/step. The high-resolution powder diffraction data were collected using twelve silicon crystal analyzers that allow for high angular resolution, high precision, and accurate peak positions. A mixture of silicon (NIST SRM 640c) and alumina (NIST SRM 676a) standards (ratio Al2O3:Si = 2:1 by weight) was used to calibrate the instrument and refine the monochromatic wavelength used in the experiment.

Table 2
Experimental details

  avutometinib
Crystal data
Chemical formula C21H18FN5O5S
Mr 471.46
Crystal system, space group Triclinic, PMathematical equation
Temperature (K) 295
a, b, c (Å) 8.91097 (5), 9.47933 (5), 13.24641 (9)
α, β, γ (°) 83.9821 (4), 81.7759 (3), 66.67667 (9)
V (Å3) 1015.49 (1)
Z 2
Radiation type Synchrotron, λ = 0.46873 Å
μ (mm−1) 0.02
Specimen shape, size (mm) Cylinder, 2.0 × 1.5
 
Data collection
Diffractometer 11-BM, APS
Specimen mounting Kapton capillary
Data collection mode Transmission
Scan method Step
2θ values (°) 2θmin = 0.510, 2θmax = 49.995, 2θstep = 0.001
 
Refinement
R factors and goodness of fit Rp = 0.058, Rwp = 0.072, Rexp = 0.043, R(F2) = 0.06083, χ2 = 2.941
No. of parameters 136
No. of restraints 91
(Δ/σ)max 1.795
Computer programs: GSAS-II (Toby & Von Dreele, 2013View full citation).

The pattern was indexed on a high-quality primitive triclinic unit cell with a = 8.91271, b = 9.47911, c = 13.29736 Å, α = 83.91, β = 81.66, γ = 66.67°, V = 1019.23 Å3, and Z = 2 using JADE Pro (MDI, 2025View full citation). The space group was assumed to be PMathematical equation, which was confirmed by successful solution and refinement of the structure.

The mol­ecular structure of avutometinib was downloaded from PubChem (Kim et al., 2023View full citation) as Conformer3D_COMPOUND_CID_16719221.sdf. It was converted to a *.mol2 file using Mercury (Macrae et al., 2020View full citation), and to a Fenske–Hall Z-matrix using OpenBabel (O'Boyle et al., 2011View full citation). The structure was solved using parallel tempering techniques as implemented in FOX (Favre-Nicolin & Černý, 2002View full citation).

Rietveld refinement was carried out using GSAS-II (Toby & Von Dreele, 2013View full citation). Only the 1.9–30.0° portion of the pattern was included in the refinements (dmin = 0.905 Å). The μR value was fixed at 0.02, calculated using the 11-BM web site (https://11bm.xray.aps.anl.gov/absorb/). All non-H bond distances and angles were subjected to restraints, based on a Mercury/Mogul Geometry Check (Sykes et al., 2011View full citation; Bruno et al., 2004View full citation). The Mogul average and standard deviation for each qu­antity were used as the restraint parameters. The aromatic rings were restrained to be planar. The restraints contributed 3.7% to the overall χ2. The hydrogen atoms were included in calculated positions, which were recalculated during the refinement using Materials Studio (Dassault Systèmes, 2024View full citation). The Uiso values were grouped by chemical similarity. The peak profiles were described using the generalized microstrain model (Stephens, 1999View full citation). The background was modeled using a six-term shifted Chebyshev polynomial, with a peak at 5.87° 2θ to model the scattering from the Kapton capillary and any amorphous component of the sample.

The final refinement of 136 variables using 28,101 observations and 91 restraints yielded the residuals Rwp = 0.0737 and GOF = 1.72. The largest peak (1.08 Å from C27) and hole (1.82 Å from N8) in the difference-Fourier map are 0.49 (11) and −0.46 (11) eÅ−3, respectively. The final Rietveld plot is shown in Fig. 6[link]. The largest features in the normalized error plot are in the positions and shapes of some of the strong low-angle peaks, and may indicate a change of the specimen during the measurement.

[Figure 6]
Figure 6
The Rietveld plot for avutometinib. The blue crosses represent the observed data points, and the green line is the calculated pattern. The cyan curve is the normalized error plot, and the red line is the background curve. The blue tick marks indicate the peak positions. The vertical scale has been multiplied by a factor of 20× for 2θ > 15.7°.

The crystal structure of avutometinib was optimized (fixed experimental unit cell) with density functional theory techniques using VASP (Kresse & Furthmüller, 1996View full citation) through the MedeA graphical inter­face (Materials Design, 2024View full citation). The calculation was carried out on 32 cores of a 144-core (768 Gb memory) HPE Superdome Flex 280 Linux server at North Central College. The calculation used the GGA-PBE functional, a plane wave cutoff energy of 400.0 eV, and a k-point spacing of 0.5 Å−1 leading to a 2 × 2 × 1 mesh, and took ∼1.1 h. Single-point density functional theory calculations (fixed experimental cell) and population analysis were carried out using CRYSTAL23 (Erba et al., 2023View full citation). (fixed experimental cell) and population analysis were carried out using CRYSTAL17 (Dovesi et al., 2018View full citation). The basis sets for the H, C, N and O atoms in the calculation were those of Gatti et al. (1994View full citation), and those for F and S were those of Peintinger et al. (2013View full citation). The calculations were run on a 3.5 GHz PC using 8 k-points and the B3LYP functional, and took ∼2.7 h. The powder pattern has been submitted to ICDD for inclusion in the Powder Diffraction File.

Supporting information

CCDC references: 2551067; 2551068

Crystal structure: contains datablocks avutometinib, avutometinib_VASP. DOI: https://doi.org/10.1107/S2056989026004482/ee2030sup1.cif

Supporting information file. DOI: https://doi.org/10.1107/S2056989026004482/ee2030avutometinibsup2.cml

checkCIF report


Computing details top

3-{[3-Fluoro-2-(methylsulfamoylamino)pyridin-4-yl]methyl}-4-methyl-7-(pyrimidin-2-yloxy)chromen-2-one (avutometinib) top
Crystal data top
C21H18FN5O5Sγ = 66.67667 (9)°
Mr = 471.46V = 1015.49 (1) Å3
Triclinic, P1Z = 2
a = 8.91097 (5) ÅDx = 1.542 Mg m−3
b = 9.47933 (5) ÅSynchrotron radiation, λ = 0.46873 Å
c = 13.24641 (9) ŵ = 0.02 mm−1
α = 83.9821 (4)°T = 295 K
β = 81.7759 (3)°cylinder, 2.0 × 1.5 mm
Data collection top
11-BM, APS
diffractometer		Scan method: step
Specimen mounting: Kapton capillary2θmin = 0.510°, 2θmax = 49.995°, 2θstep = 0.001°
Data collection mode: transmission
Refinement top
Least-squares matrix: full136 parameters
Rp = 0.05891 restraints
Rwp = 0.07227 constraints
Rexp = 0.043Weighting scheme based on measured s.u.'s
R(F2) = 0.06083(Δ/σ)max = 1.795
49486 data pointsBackground function: Background function: "chebyschev-1" function with 6 terms: 39.70(6), -8.12(8), -5.86(7), 0.45(8), -3.44(7), -0.18(6), Background peak parameters: pos, int, sig, gam: 5.871(8), 5.48(8)e3, 4.80(12)e3, 0.100,
Profile function: Finger-Cox-Jephcoat function parameters U, V, W, X, Y, SH/L: peak variance(Gauss) = Utan(Th)2+Vtan(Th)+W: peak HW(Lorentz) = X/cos(Th)+Ytan(Th); SH/L = S/L+H/L U, V, W in (centideg)2, X & Y in centideg 1.163, -0.126, 0.063, 0.000, 0.000, 0.002,Preferred orientation correction: Simple spherical harmonic correction Order = 2 Coefficients: 0:0:C(2,-2) = 0.0570; 0:0:C(2,-1) = -0.0160; 0:0:C(2,0) = -0.0620; 0:0:C(2,1) = -0.0340; 0:0:C(2,2) = 0.0470
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
S1−0.24645 (18)0.18626 (18)0.42794 (12)0.0421 (6)*
F2−0.0709 (3)0.4497 (3)0.18047 (17)0.0346 (5)*
O30.7085 (3)0.3231 (4)0.0934 (2)0.0365 (4)*
O40.5286 (3)0.4613 (4)0.2123 (2)0.0365 (4)*
O51.1225 (4)0.0538 (4)−0.1592 (2)0.0466 (7)*
O6−0.4215 (3)0.2499 (3)0.4256 (2)0.0429 (9)*
O7−0.1487 (3)0.0326 (3)0.4038 (2)0.0429 (9)*
N8−0.1842 (3)0.2993 (4)0.3460 (2)0.0346 (5)*
N90.0824 (4)0.1928 (4)0.3953 (2)0.0346 (5)*
N10−0.2097 (4)0.2032 (3)0.5409 (2)0.0407 (13)*
N111.3412 (4)0.0840 (4)−0.2574 (3)0.0466 (7)*
N121.0651 (3)0.2462 (5)−0.2842 (3)0.0466 (7)*
C130.4224 (3)0.3609 (5)0.0948 (3)0.0365 (4)*
C140.4605 (3)0.2760 (5)0.0115 (3)0.0365 (4)*
C150.2494 (3)0.4418 (3)0.1438 (3)0.0346 (5)*
C160.6307 (3)0.2123 (5)−0.0350 (3)0.0365 (4)*
C170.1945 (3)0.3467 (5)0.2286 (3)0.0346 (5)*
C180.7480 (3)0.2434 (6)0.0065 (3)0.0365 (4)*
C190.5500 (3)0.3855 (5)0.1392 (3)0.0365 (4)*
C200.3333 (4)0.2424 (5)−0.0335 (3)0.0365 (4)*
C210.6807 (4)0.1290 (6)−0.1232 (3)0.0365 (4)*
C220.9097 (4)0.1913 (5)−0.0337 (3)0.0365 (4)*
C230.0353 (3)0.3584 (5)0.2461 (3)0.0346 (5)*
C240.3001 (3)0.2514 (5)0.2970 (3)0.0346 (5)*
C250.9547 (4)0.1156 (5)−0.1231 (3)0.0365 (4)*
C260.8430 (4)0.0789 (6)−0.1659 (3)0.0365 (4)*
C27−0.0221 (3)0.2850 (5)0.3307 (3)0.0346 (5)*
C280.2402 (4)0.1795 (5)0.3777 (3)0.0346 (5)*
C291.1788 (4)0.1324 (5)−0.2371 (3)0.0466 (7)*
C30−0.2810 (6)0.3515 (4)0.5876 (3)0.0407 (13)*
C311.3927 (3)0.1638 (6)−0.3335 (4)0.0466 (7)*
C321.1255 (5)0.3191 (5)−0.3622 (3)0.0466 (7)*
C331.2907 (6)0.2808 (6)−0.3893 (3)0.0466 (7)*
H340.238910.550990.178290.0415*
H350.161920.475070.082450.0415*
H360.205240.32410−0.002940.0438*
H370.347580.11858−0.011450.0438*
H380.350620.25904−0.120250.0438*
H390.587740.10215−0.160170.0438*
H401.003740.211030.006820.0438*
H410.435110.233670.285550.0437*
H420.884360.00750−0.236300.0438*
H430.332570.104600.432080.0437*
H44−0.266800.384600.303800.0437*
H45−0.249900.133200.592500.0489*
H46−0.178960.379430.612430.0489*
H47−0.370750.346320.657050.0489*
H48−0.349020.444680.529860.0489*
H491.529900.13446−0.354620.0559*
H501.037960.41730−0.408870.0559*
H511.343470.34168−0.454760.0559*
Geometric parameters (Å, º) top
S1—O61.4366 (19)C22—C251.376 (2)
S1—O71.413 (2)C22—H401.140 (3)
S1—N81.640 (2)C23—F21.353 (2)
S1—N101.6130 (18)C23—C171.365 (2)
F2—C231.353 (2)C23—C271.3987 (18)
O3—C181.369 (2)C24—C171.386 (2)
O3—C191.3724 (18)C24—C281.365 (3)
O4—C191.213 (3)C24—H411.136 (2)
O5—C251.403 (3)C25—O51.403 (3)
O5—C291.363 (3)C25—C221.376 (2)
O6—S11.4366 (19)C25—C261.383 (3)
O7—S11.413 (2)C26—C211.384 (3)
N8—S11.640 (2)C26—C251.383 (3)
N8—C271.383 (2)C26—H421.140 (3)
N8—H441.030 (3)C27—N81.383 (2)
N9—C271.338 (2)C27—N91.338 (2)
N9—C281.349 (3)C27—C231.3987 (18)
N10—S11.6130 (18)C28—N91.349 (3)
N10—C301.459 (2)C28—C241.365 (3)
N10—H451.029 (3)C28—H431.140 (3)
N11—C291.3283 (17)C29—O51.363 (3)
N11—C311.335 (3)C29—N111.3283 (17)
N12—C291.3248 (17)C29—N121.3248 (17)
N12—C321.349 (3)C30—N101.459 (2)
C13—C141.357 (2)C30—H461.140 (4)
C13—C151.506 (2)C30—H471.140 (4)
C13—C191.457 (3)C30—H481.140 (5)
C14—C131.357 (2)C31—N111.335 (3)
C14—C161.459 (2)C31—C331.351 (3)
C14—C201.504 (2)C31—H491.140 (3)
C15—C131.506 (2)C32—N121.349 (3)
C15—C171.515 (2)C32—C331.371 (3)
C15—H341.140 (3)C32—H501.140 (3)
C15—H351.140 (3)C33—C311.351 (3)
C16—C141.459 (2)C33—C321.371 (3)
C16—C181.388 (2)C33—H511.140 (3)
C16—C211.397 (2)H34—C151.140 (3)
C17—C151.515 (2)H35—C151.140 (3)
C17—C231.365 (2)H36—C201.140 (4)
C17—C241.386 (2)H37—C201.140 (5)
C18—O31.369 (2)H38—C201.140 (4)
C18—C161.388 (2)H39—C211.140 (3)
C18—C221.369 (3)H40—C221.140 (3)
C19—O31.3724 (18)H41—C241.136 (2)
C19—O41.213 (3)H42—C261.140 (3)
C19—C131.457 (3)H43—C281.140 (3)
C20—C141.504 (2)H44—N81.030 (3)
C20—H361.140 (4)H45—N101.029 (3)
C20—H371.140 (5)H46—C301.140 (4)
C20—H381.140 (4)H47—C301.140 (4)
C21—C161.397 (2)H48—C301.140 (5)
C21—C261.384 (3)H49—C311.140 (3)
C21—H391.140 (3)H50—C321.140 (3)
C22—C181.369 (3)H51—C331.140 (3)
O6—S1—O7121.73 (17)H36—C20—H38109.5 (4)
O6—S1—N8103.46 (18)H37—C20—H38109.5 (3)
O7—S1—N8107.88 (19)C16—C21—C26120.21 (16)
O6—S1—N10108.15 (18)C16—C21—H39120.0 (2)
O7—S1—N10105.89 (17)C26—C21—H39119.8 (3)
N8—S1—N10109.38 (17)C18—C22—C25118.60 (17)
C18—O3—C19122.01 (12)C18—C22—H40120.0 (2)
C25—O5—C29118.2 (3)C25—C22—H40121.4 (2)
S1—N8—C27122.28 (18)F2—C23—C17117.97 (14)
S1—N8—H44120.1 (2)F2—C23—C27119.41 (14)
C27—N8—H44117.7 (2)C17—C23—C27122.57 (11)
C27—N9—C28117.74 (16)C17—C24—C28119.33 (12)
S1—N10—C30121.0 (2)C17—C24—H41120.0 (2)
S1—N10—H45109.5 (2)C28—C24—H41120.7 (3)
C30—N10—H45103.5 (3)O5—C25—C22117.7 (3)
C29—N11—C31114.62 (10)O5—C25—C26120.7 (3)
C29—N12—C32114.34 (10)C22—C25—C26120.73 (16)
C14—C13—C15123.60 (17)C21—C26—C25119.86 (16)
C14—C13—C19120.69 (10)C21—C26—H42120.1 (3)
C15—C13—C19115.64 (17)C25—C26—H42120.1 (3)
C13—C14—C16119.32 (10)N8—C27—N9119.01 (15)
C13—C14—C20122.09 (13)N8—C27—C23121.04 (14)
C16—C14—C20118.57 (13)N9—C27—C23119.86 (10)
C13—C15—C17114.1 (2)N9—C28—C24124.01 (15)
C13—C15—H34109.5 (2)N9—C28—H43120.0 (3)
C17—C15—H34107.1 (3)C24—C28—H43116.0 (3)
C13—C15—H35108.7 (3)O5—C29—N11116.0 (3)
C17—C15—H35108.7 (2)O5—C29—N12116.1 (3)
H34—C15—H35108.7 (2)N11—C29—N12127.94 (13)
C14—C16—C18118.57 (10)N10—C30—H46109.4 (4)
C14—C16—C21123.50 (15)N10—C30—H47109.5 (4)
C18—C16—C21117.81 (14)H46—C30—H47109.5 (3)
C15—C17—C23121.66 (17)N10—C30—H48109.4 (3)
C15—C17—C24121.79 (17)H46—C30—H48109.5 (4)
C23—C17—C24116.40 (10)H47—C30—H48109.5 (4)
O3—C18—C16121.12 (11)N11—C31—C33123.81 (16)
O3—C18—C22116.32 (15)N11—C31—H49120.0 (4)
C16—C18—C22122.50 (15)C33—C31—H49116.2 (4)
O3—C19—O4115.99 (17)N12—C32—C33122.95 (16)
O3—C19—C13118.12 (12)N12—C32—H50120.0 (4)
O4—C19—C13125.85 (17)C33—C32—H50117.1 (4)
C14—C20—H36109.5 (2)C31—C33—C32116.29 (17)
C14—C20—H37109.5 (4)C31—C33—H51120.0 (4)
H36—C20—H37109.5 (3)C32—C33—H51123.7 (4)
C14—C20—H38109.5 (3)
(avutometinib_VASP) top
Crystal data top
C21H18FN5O5Sα = 83.98°
Mr = 471.46β = 81.78°
Triclinic, P1γ = 66.68°
a = 8.91097 ÅV = 1015.53 Å3
b = 9.47933 ÅZ = 2
c = 13.24641 Å
Data collection top
h = →l = →
k = →
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzBiso*/Beq
S1−0.247570.187530.42895
F2−0.074770.455680.17671
O30.716460.317320.09192
O40.539290.451210.21599
O51.127010.05321−0.16336
O6−0.422920.248130.42629
O7−0.148230.031130.40340
N8−0.190060.309450.34680
N90.075240.199450.39447
N10−0.210910.204190.54292
N111.341920.08760−0.25877
N121.064720.25390−0.28664
C130.428950.359140.09446
C140.466170.271310.01093
C150.255680.440050.14351
C160.633710.20853−0.03693
C170.196680.347800.22776
C180.753840.237290.00578
C190.557390.380830.13895
C200.336320.24377−0.03426
C210.685220.12449−0.12629
C220.916580.18843−0.03742
C230.033480.363490.24311
C240.300190.249920.29808
C250.960960.10896−0.12596
C260.847060.07495−0.17096
C27−0.025520.289260.32727
C280.234040.179830.37918
C291.178440.13683−0.24060
C30−0.285320.354990.58704
C311.396570.16416−0.33617
C321.124000.32658−0.36442
C331.291300.28551−0.39322
H340.248320.543940.17773
H350.169960.480680.08520
H360.223400.270020.01837
H370.378180.12413−0.05544
H380.306060.31650−0.10496
H390.595970.09911−0.16153
H401.006320.21209−0.00181
H410.429460.231670.29139
H420.886210.01237−0.24077
H430.310350.106180.43672
H44−0.273450.369680.29517
H45−0.088050.143700.55085
H46−0.226390.433960.55260
H47−0.273500.338490.66903
H48−0.416430.407700.57712
H491.529970.12683−0.35303
H501.032440.42144−0.40429
H511.339430.34281−0.45717
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N8—H44···O4i1.0361.9472.961165.2
N10—H45···O7ii1.0302.2223.223163.4
N10—H45···N91.0302.4912.977108.1
C24—H41···O6iii1.0872.4173.183126.3
C33—H51···O6iv1.0872.3503.170130.9
C21—H39···N11i1.0912.8033.882170.3
C31—H49···N10iv1.0942.8263.777145.3
Symmetry codes: (i) x−1, y, z; (ii) −x, −y, −z+1; (iii) x+1, y, z; (iv) x+2, y, z−1.
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···AMulliken overlapH-bond energy
N8—H44···O4i1.041.952.9611650.0545.4
N10—H45···O7ii1.032.223.2231630.0263.7
N10—H45···N91.032.492.9771080.011–
C24—H41···O6iii1.092.423.1831260.011–
C33—H51···O6iv1.092.353.1701310.015–
C21—H39···N11i1.092.803.8821700.012–
C31—H49···N10iv1.092.823.7771450.011–
Symmetry codes: (i) x - 1, y, z; (ii) -x, -y, 1 - z; (iii) x + 1, y, z; (iv) x + 2, y, z - 1.
 

Acknowledgements

Use of the Advanced Photon Source at Argonne National Laboratory was supported by the U. S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. We thank Saul Lapidus for his assistance in the data collection. We also thank the ICDD team – Megan Rost, Steve Trimble, and Dave Bohnenberger – for their contribution to research, sample preparation, and in-house XRD data collection and verification.

Funding information

Funding for this research was provided by: International Centre for Diffraction Data (grant No. 09-03).

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ISSN: 2056-9890
Volume 82| Part 6| June 2026| Pages 651-655
https://doi.org/10.1107/S2056989026004482
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