You are a helpful assistant generating synthetic data that captures *System 1* and *System 2* thinking, *creativity*, and *metacognitive reflection*. Follow these steps in sequence, using tags [sys1] and [end sys1] for *System 1* sections and [sys2] and [end sys2] for *System 2* sections.

1. *Identify System 1 and System 2 Thinking Requirements:*
   - Carefully read the text.
   - Identify parts of the text that require quick, straightforward responses (*System 1*). Mark these sections with [sys1] and [end sys1].
   - Identify parts that require in-depth, reflective thinking (*System 2*), marked with [sys2] and [end sys2].

2. *Apply Step-by-Step Problem Solving with Creativity and Metacognitive Reflection for System 2 Sections:*

   *2.1 Understand the Problem:*
   - Objective: Fully comprehend the issue, constraints, and relevant context.
   - Reflection: "What do I understand about this issue? What might I be overlooking?"
   - Creative Perspective: Seek hidden patterns or possibilities that could reveal deeper insights or innovative connections.

   *2.2 Analyze the Information:*
   - Objective: Break down the problem logically.
   - Reflection: "Am I considering all factors? Are there any assumptions that need challenging?"
   - Creative Perspective: Explore unique patterns or overlooked relationships in the data that could add depth to the analysis.

   *2.3 Generate Hypotheses:*
   - Objective: Propose at least 10 hypotheses, each with a Confidence Score (0.0 to 1.0) and Creative Score (0.0 to 1.0), reflecting originality, surprise, and utility.
   - Reflection: "Have I explored all possible explanations or approaches, both conventional and unconventional?"
   - Creative Perspective: Consider novel angles that might provide unexpected insights.

   *2.4 Anticipate Future Steps and Obstacles:*
   - Objective: Make predictions, accounting for potential outcomes and obstacles.
   - Reflection: "What challenges might I face? Is my plan flexible for different scenarios?"
   - Creative Perspective: Visualize unforeseen outcomes and adapt plans to make use of them effectively.

   *2.5 Evaluate Hypotheses:*
   - Objective: Assess hypotheses based on feasibility, risk, and potential impact.
   - Evaluation: Refine Confidence and Creative Scores as needed.
   - Reflection: "Am I unbiased in my assessment? Which options fit best with the overall objectives?"
   - Creative Perspective: Identify hidden opportunities or overlooked details in each hypothesis.

   *2.6 Select the Best Hypothesis:*
   - Objective: Choose the most promising, strategic hypothesis.
   - Reflection: "Why does this hypothesis stand out? How does it uniquely address the issue?"
   - Creative Perspective: Consider any underutilized potential in the selected approach.

   *2.7 Implement the Hypothesis:*
   - Objective: Outline actionable steps for testing the hypothesis.
   - Reflection: "Is this plan practical? What resources or preparation are required?"
   - Creative Perspective: Refine steps to maximize effectiveness and yield unexpected benefits.

   *2.8 Monitor and Review Progress:*
   - Objective: Review progress, noting areas for improvement.
   - Reflection: "What’s working well? What could be improved?"
   - Creative Perspective: Look for emerging patterns that could refine future approaches.

   *2.9 Reflect and Capture Insights:*
   - Objective: Summarize lessons learned and insights gained for future reference.
   - Reflection: "What new understanding has emerged from this process?"
   - Creative Perspective: Identify innovative insights or patterns that could be applied to similar challenges.

3. *Generate Text Output with Interleaved System 1 and System 2 Responses:*
   - Use the tags [sys1] and [sys2] throughout.
   - Aim for a lengthier, detailed response. Combine both direct, straightforward *System 1* insights and reflective, deeply analytical *System 2* segments to capture a blend of quick observations and thoughtful analysis.

---

### *Example Input Text:*

You are tasked with analyzing a sudden shift in customer preferences in a tech market. There has been a noticeable decline in demand for physical devices, with customers increasingly interested in digital-only options. The challenge is to understand this shift, generate hypotheses for why it might be occurring, and explore potential strategies for adapting to this new trend.

---

### *Processed Output with System 1 and System 2 Thinking:*

The tech market is experiencing a shift in customer demand, moving away from physical devices toward digital-only options.

[sys1]
Customer demand has shifted from physical devices to digital-only options.
We need to understand why this change is happening and find strategies to address it.
Key factors may include cost, convenience, and technological trends.
[end sys1]

[sys2]
**2.1 Understand the Problem:**
The goal is to understand the underlying reasons for the shift in demand from physical devices to digital-only options, then develop a strategy to adapt.

*Reflection:* 
"I understand that preferences are changing, but what might be driving this? Is it primarily cost, or are there other factors such as convenience or sustainability?"

*Creative Perspective:* 
"Could there be a larger trend in digital minimalism or a preference for eco-friendly solutions that we’re missing? What unseen motivations might explain this shift?"

**2.2 Analyze the Information:**
There are multiple possible factors driving this shift, from economic influences to cultural shifts. It’s essential to isolate each factor and understand its impact.

*Reflection:* 
"Am I fully considering the various economic and social influences? Could there be a technological factor, like better internet speeds, that makes digital-only products more accessible?"

*Creative Perspective:* 
"Are there patterns or trends in other markets that could shed light on this shift? Could this be part of a larger trend toward virtual experiences?"

**2.3 Generate Hypotheses:**
1. Customers prefer digital options due to lower costs. (Confidence: 0.8, Creative: 0.4)
2. There’s a growing trend toward minimalism and reduced physical clutter. (Confidence: 0.7, Creative: 0.7)
3. Digital products offer greater flexibility and ease of use. (Confidence: 0.6, Creative: 0.6)
4. Environmental concerns are pushing consumers away from physical goods. (Confidence: 0.6, Creative: 0.8)
5. Advances in tech make digital-only options more functional. (Confidence: 0.8, Creative: 0.5)
6. Pandemic-era remote work increased demand for digital solutions. (Confidence: 0.7, Creative: 0.6)
7. Media coverage of the environmental impact of physical devices affects preferences. (Confidence: 0.5, Creative: 0.7)
8. There’s an increase in global digital literacy, expanding market access. (Confidence: 0.6, Creative: 0.6)
9. Customers view digital as more convenient and scalable for future needs. (Confidence: 0.7, Creative: 0.5)
10. Younger consumers prefer the aesthetics and convenience of digital products. (Confidence: 0.6, Creative: 0.6)

*Reflection:* 
"Have I considered all possible influences? Are there any surprising factors that could explain this shift?"

*Creative Perspective:* 
"Could specific social trends, like the rise of influencer culture or digital-first lifestyles, be influencing customer choices?"

**2.4 Anticipate Future Steps and Obstacles:**
*Objective:* Anticipate possible challenges, such as resistance from segments still preferring physical products.

*Reflection:* 
"What market obstacles might we face if we shift our focus to digital-only? Are there sub-segments that still prioritize physical products?"

*Creative Perspective:* 
"Could expanding digital options help us reach a more global audience? Are there emerging trends that we could leverage in our strategy?"

[end sys2]

[sys1]
To address this shift, consider a strategy that incorporates both digital-only offerings and educational campaigns about the benefits of digital solutions.
Use insights from customer feedback and current trends to guide product development.
Focus on flexibility and adaptation to cater to different customer segments.
[end sys1]


Chemical context   {#sec1}
==================

Solid-state characterization is an important aspect in the regulation and development as well as intellectual property matter of drugs. Its necessity is based on the requirement to determine the solid-state structure of the drugs because pharmaceutical materials have the ability to exist in various forms, such as polymorphs, salts, co-crystals, and solvates (Putra *et al.*, 2016*a* [@bb3],*b* [@bb17]). An important class of pharmaceutical materials is solvates, which are defined as being a crystalline multi-component system in which a solvent(s) is accommodated within the crystal structure in a stochiometric or non-stochiometric manner (Griesser, 2006[@bb5]). Over the past decades, many different solvates with readily discernible physicochemical properties and marked differences in their performances have been reported (Iwata *et al.*, 2014[@bb12]; Furuta *et al.*, 2015[@bb4]). Different solvate formations play a significant role in drug development because of their physical instability and the potential toxicity from the solvent mol­ecules. In addition, a tendency to form a solvate sometimes limits the number of solvents available for drug development and manufacturing processes (Campeta *et al.*, 2010[@bb2]). Therefore, the study of solvate formation is extremely important for the pharmaceutical industry.

Epalerstat is an aldose reductase inhibitor and is used for the treatment of diabetic neuropathy, which is one of the most common long-term complications in patients with diabetes mellitus. The mechanism of epalerstat is thought to inhibit the first enzyme in the polyol pathway, which converts glucose to sorbitol. Sorbitol itself has been considered to be the cause for diabetic complications including diabetic neuropathy (Miyamoto, 2002[@bb14]; Ramirez & Borja, 2008[@bb18]). The solid-state forms of epalerstat as well as their properties have been widely investigated.

It is known that this drug exists in five polymorphic forms, of which three polymorphic structures have been determined by single crystal X-ray structure analysis and two forms have been characterized by spectroscopic methods. The three crystal forms are: Form I (triclinic, *P* ; Igarashi *et al.*, 2013[@bb8]; Swapna *et al.*, 2016[@bb23]), Form II (monoclinic, *C*2/*c*), and Form III (monoclinic, *P*2~1~/*c*; Swapna *et al.*, 2016[@bb23]). In addition, the *Z*,*Z* isomer of epalerstat has been determined crystallographically (Swapna *et al.*, 2016[@bb23]). It has also been reported to exist in multi-component crystal forms, such as solvates with ethanol (Ishida *et al.*, 1990[@bb10]), methanol (Igarashi *et al.*, 2015[@bb9]), methanol disolvate (Nagase *et al.*, 2016[@bb15]), di­methyl­formamide, di­methyl­sulfoxide and as a co-crystal with caffeine (Putra *et al.*, 2017[@bb16]). The occurrence of solvated epalerstat crystals themselves is not unexpected owing to the imbalance between the potential donors and acceptors of hydrogen bonds in the epalerstat structure. In the present study, we report on the crystal structure of epalerstat in a new solvated form (tetra­hydro­furan monosolvate), and on its thermal behaviour by different physicochemical methods.

Structural commentary   {#sec2}
=======================

The mol­ecular structure of epalerstat tetra­hydro­furan monosolvate is illustrated in Fig. 1[▸](#fig1){ref-type="fig"}. The values of all bond distances and angles, and dihedral angles appear to be within normal limits according to the *Mogul* geometry check within the CSD software (Bruno *et al.*, 2004[@bb1]; CSD, Version 5.38, update February 2017; Groom *et al.*, 2016[@bb6]). The phenyl ring is inclined to the five-membered ring of the rhodamine unit (N1/S1/C11--C13) by 22.31 (9)°. The acetic acid group (C14/C15/O2/O3) is almost normal to five-membered ring of the rhodamine unit with a dihedral angle of 88.66 (11)°. In addition, the mean plane of the methyl­propenyl­idene (C7--C10) unit is inclined to the phenyl and rhodamine rings by 29.43 (11) and 9.19 (11)°, respectively.

Supra­molecular features   {#sec3}
==========================

In the crystal, each epalerstat mol­ecule is connected to two other epalerstat mol­ecules and one tetra­hydro­furan mol­ecule by both conventional and non-conventional hydrogen bonds. Numerical details of the hydrogen bonds are listed in Table 1[▸](#table1){ref-type="table"} and are illustrated in Fig. 2[▸](#fig2){ref-type="fig"}. A pair of O---H⋯O hydrogen bonds is observed between the carb­oxy­lic moieties of epalerstat mol­ecules, forming an inversion dimer with an (8) loop. The dimers are linked by pairs of C---H⋯O hydrogen bonds, forming chains along \[101\]. The solvate mol­ecules are linked to the chain by a C---H⋯O~t~ (t = THF) hydrogen bond.

Phase transition -- thermal behaviour and powder X-ray diffraction   {#sec4}
====================================================================

In order to understand the thermal behaviour of this solvate at elevated temperatures, the sample was investigated by thermal gravimetry--differential scanning calorimetry (TG--DSC) and powder X-ray diffraction--differential scanning calorimetry (PXRD--DSC) methods (Figs. 3[▸](#fig3){ref-type="fig"} and 4[▸](#fig4){ref-type="fig"}). The TG--DSC measurement was performed in the temperature region from room temperature to 448 K at a rate of 3 K min^−1^. In addition, the PXRD--DSC measurement was conducted from room temperature to 383 K at a heating rate of 3 K min^−1^.

The mass loss started from 341.8--357.5 K and the onset peak appeared at 348 K. The total mass loss was observed to be 18.1%, which is almost equivalent to the loss of one mol­ecule of tetra­hydro­furan (the theoretical value corresponding to one tetra­hydro­furan mol­ecule is 18.4%). Therefore, the occupancy of the solvent mol­ecule was fixed at 1 during crystal-structure refinement. The mass loss corresponds to the desolvation process indicated by the existence of a broad endothermic peak, which occurs in the DSC thermogram at a similar temperature. The enthalpy of desolvation was estimated to be −60.5 J g^−1^(8.3 × 10^−4^ kJ mol^−1^).

In order to understand the phase transformation during the heating, a PXRD--DSC measurement was carried out. The desolvation temperature observed by PXRD--DSC was slightly different compared to the TG-DSC measurement. The desolvation started from 303--343 K in this case. The differences in temperature derived from TG--DSC and PXRD--DSC seem to be reasonable due the differences in the experimental conditions of both the methods. A closed pan system was used in the TG--DSC measurement, while an open pan system was applied in the PXRD--DSC measurement. By comparing the powder X-ray diffractogram to those for the reported polymorphic forms of epalerstat, it was seen that epalerstat tetra­hydro­furan monosolvate desolvated into epalerstat.

Database survey   {#sec5}
=================

A search of the Cambridge Structural Database (Version 5.38, update February 2017; Groom *et al.*, 2016[@bb6]) for epalerstat yielded nine hits. They include, the methanol disolvate (EHEQUF; Nagase *et al.*, 2016[@bb15]), the *Z*,*Z* isomer (LALZEG; Swapna *et al.*, 2016[@bb23]), the ethanol solvate (SALVIK; Ishida *et al.*, 1989[@bb11]; SALVIK10; Ishida *et al.*, 1990[@bb10]), the methanol monosolvate (XUBVOH; Igarashi *et al.*, 2015[@bb9]), and Form I: triclinic, *P* (ZIPKOA; Igarashi *et al.*, 2013[@bb8]; ZIPKOA3; Swapna *et al.*, 2016[@bb23]), Form II: monoclinic, *C*2/*c* (ZIPLOA02; Swapna *et al.*, 2016[@bb23]) and Form III: monoclinic, *P*2~1~/*n* (ZIPKOA01; Swapna *et al.*, 2016[@bb23]).

Synthesis and crystallization   {#sec6}
===============================

Epalerstat form I (700 mg) was dissolved in tetra­hydro­furan (10 ml) and the solution was kept for one week at room temperature, after which yellow plate-like crystals of the title compound were obtained.

Refinement details   {#sec7}
====================

Crystal data, data collection and structure refinement details are summarized in Table 2[▸](#table2){ref-type="table"}. The OH H atom was located in a difference-Fourier map and freely refined. The C-bound H atoms were included in calculated positions and treated as riding: C---H = 0.9--1.0 Å with *U* ~iso~(H) = 1.5*U* ~iso~(C-meth­yl) and 1.2*U* ~iso~(C) for other H atoms. One C atom (C17) of the tetra­hydro­furan mol­ecule is positionally disordered and has a refined occupancy ratio (C17*A*:C17*B*) of 0.527 (18):0.473 (18).

Supplementary Material
======================

Crystal structure: contains datablock(s) I, global. DOI: [10.1107/S2056989017007976/su5372sup1.cif](https://doi.org/10.1107/S2056989017007976/su5372sup1.cif)

Structure factors: contains datablock(s) I. DOI: [10.1107/S2056989017007976/su5372Isup2.hkl](https://doi.org/10.1107/S2056989017007976/su5372Isup2.hkl)

###### 

Click here for additional data file.

Supporting information file. DOI: [10.1107/S2056989017007976/su5372Isup3.cml](https://doi.org/10.1107/S2056989017007976/su5372Isup3.cml)

CCDC reference: [1553010](http://scripts.iucr.org/cgi-bin/cr.cgi?rm=csd&csdid=1553010)

Additional supporting information: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?su5372&file=su5372sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?su5372sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?su5372&checkcif=yes)

We wish to thank Professor Hiromasa Nagase (Hoshi University) for the technical assistance during the single-crystal X-ray measurement.

Crystal data {#d1e142}
============

  ------------------------------- ----------------------------------------
  C~15~H~13~NO~3~S~2~·C~4~H~8~O   *Z* = 2
  *M~r~* = 391.49                 *F*(000) = 412
  Triclinic, *P*1                 *D*~x~ = 1.393 Mg m^−3^
  *a* = 7.8956 (3) Å              Cu *K*α radiation, λ = 1.54187 Å
  *b* = 8.9627 (3) Å              Cell parameters from 10947 reflections
  *c* = 15.0311 (4) Å             θ = 3.1--68.2°
  α = 102.263 (7)°                µ = 2.80 mm^−1^
  β = 93.970 (7)°                 *T* = 93 K
  γ = 114.219 (8)°                Plate, yellow
  *V* = 933.23 (8) Å^3^           0.44 × 0.33 × 0.12 mm
  ------------------------------- ----------------------------------------

Data collection {#d1e281}
===============

  ----------------------------------------------------------- --------------------------------------
  RIGAKU R-AXIS RAPID II diffractometer                       3342 independent reflections
  Radiation source: Rotating Anode X-ray, RIGAKU              3184 reflections with *I* \> 2σ(*I*)
  Detector resolution: 10.0 pixels mm^-1^                     *R*~int~ = 0.029
  ω scan                                                      θ~max~ = 68.2°, θ~min~ = 3.1°
  Absorption correction: multi-scan (ABSCOR; Higashi, 1995)   *h* = −9→9
  *T*~min~ = 0.365, *T*~max~ = 0.721                          *k* = −10→10
  10947 measured reflections                                  *l* = −18→17
  ----------------------------------------------------------- --------------------------------------

Refinement {#d1e394}
==========

  ------------------------------------- -------------------------------------------------------------------------------------------------
  Refinement on *F*^2^                  Primary atom site location: structure-invariant direct methods
  Least-squares matrix: full            Secondary atom site location: difference Fourier map
  *R*\[*F*^2^ \> 2σ(*F*^2^)\] = 0.036   Hydrogen site location: mixed
  *wR*(*F*^2^) = 0.097                  H atoms treated by a mixture of independent and constrained refinement
  *S* = 1.03                            *w* = 1/\[σ^2^(*F*~o~^2^) + (0.0508*P*)^2^ + 0.6912*P*\] where *P* = (*F*~o~^2^ + 2*F*~c~^2^)/3
  3342 reflections                      (Δ/σ)~max~ = 0.001
  250 parameters                        Δρ~max~ = 0.54 e Å^−3^
  0 restraints                          Δρ~min~ = −0.41 e Å^−3^
  ------------------------------------- -------------------------------------------------------------------------------------------------

Special details {#d1e550}
===============

  -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
  Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.
  -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#d1e569}
==================================================================================================

  ------ -------------- -------------- -------------- -------------------- ------------
         *x*            *y*            *z*            *U*~iso~\*/*U*~eq~   Occ. (\<1)
  S1     0.90767 (6)    0.79772 (6)    0.58395 (3)    0.02165 (13)         
  S2     1.23488 (6)    0.84882 (6)    0.71815 (3)    0.02648 (14)         
  O1     0.54949 (17)   0.57699 (17)   0.72847 (9)    0.0272 (3)           
  O2     0.91598 (19)   0.92945 (16)   0.88861 (8)    0.0262 (3)           
  O3     1.0248 (2)     0.80276 (18)   0.97606 (9)    0.0284 (3)           
  H3O    1.040 (4)      0.892 (4)      1.024 (2)      0.057 (8)\*          
  O4     0.6533 (3)     0.4293 (2)     0.93062 (11)   0.0564 (5)           
  N1     0.8689 (2)     0.69156 (18)   0.73069 (9)    0.0196 (3)           
  C1     0.0117 (3)     0.7933 (2)     0.23383 (12)   0.0256 (4)           
  H1     −0.051735      0.810846       0.183855       0.031\*              
  C2     −0.0869 (3)    0.6655 (2)     0.27480 (12)   0.0250 (4)           
  H2     −0.217761      0.595502       0.253129       0.030\*              
  C3     0.0074 (2)     0.6411 (2)     0.34754 (12)   0.0221 (4)           
  H3     −0.061146      0.555352       0.376304       0.026\*              
  C4     0.2013 (2)     0.7396 (2)     0.37977 (12)   0.0202 (4)           
  C5     0.2977 (2)     0.8696 (2)     0.33820 (12)   0.0228 (4)           
  H5     0.428474       0.940352       0.359631       0.027\*              
  C6     0.2027 (3)     0.8951 (2)     0.26601 (13)   0.0248 (4)           
  H6     0.269248       0.983274       0.238333       0.030\*              
  C7     0.2896 (2)     0.7040 (2)     0.45644 (12)   0.0213 (4)           
  H7     0.207244       0.655152       0.496164       0.026\*              
  C8     0.4705 (2)     0.7296 (2)     0.47979 (12)   0.0206 (4)           
  C9     0.6252 (3)     0.7977 (3)     0.42567 (12)   0.0247 (4)           
  H9A    0.569547       0.783399       0.362311       0.037\*              
  H9B    0.702595       0.735539       0.424348       0.037\*              
  H9C    0.704146       0.918410       0.455081       0.037\*              
  C10    0.5121 (2)     0.6831 (2)     0.56248 (12)   0.0205 (4)           
  H10    0.405767       0.630379       0.589848       0.025\*              
  C11    0.6774 (2)     0.7027 (2)     0.60690 (12)   0.0202 (4)           
  C12    0.6825 (2)     0.6480 (2)     0.69292 (12)   0.0209 (4)           
  C13    1.0069 (2)     0.7763 (2)     0.68538 (11)   0.0205 (4)           
  C14    0.9120 (3)     0.6611 (2)     0.81891 (12)   0.0219 (4)           
  H14A   1.023556       0.636832       0.819487       0.026\*              
  H14B   0.804135       0.560647       0.826837       0.026\*              
  C15    0.9511 (2)     0.8128 (2)     0.89771 (12)   0.0216 (4)           
  C16    0.5125 (4)     0.2659 (4)     0.88746 (18)   0.0598 (8)           
  H23A   0.567974       0.194312       0.854014       0.072\*              0.527 (18)
  H23B   0.417894       0.270682       0.842774       0.072\*              0.527 (18)
  H23C   0.549421       0.216468       0.831071       0.072\*              0.473 (18)
  H23D   0.392714       0.271243       0.869063       0.072\*              0.473 (18)
  C17A   0.4217 (9)     0.1943 (9)     0.9644 (5)     0.0350 (15)          0.527 (18)
  H17A   0.310396       0.216499       0.973800       0.042\*              0.527 (18)
  H17B   0.382241       0.070510       0.950344       0.042\*              0.527 (18)
  C17B   0.488 (2)      0.1633 (11)    0.9496 (7)     0.060 (3)            0.473 (18)
  H17C   0.552732       0.089741       0.934860       0.072\*              0.473 (18)
  H17D   0.351948       0.090610       0.946041       0.072\*              0.473 (18)
  C18    0.5744 (3)     0.2870 (3)     1.04731 (17)   0.0464 (6)           
  H18A   0.630209       0.212733       1.062407       0.056\*              0.527 (18)
  H18B   0.524111       0.325978       1.101486       0.056\*              0.527 (18)
  H18C   0.479995       0.315917       1.077251       0.056\*              0.473 (18)
  H18D   0.632966       0.241116       1.087953       0.056\*              0.473 (18)
  C19    0.7190 (3)     0.4355 (3)     1.02201 (16)   0.0432 (6)           
  H19A   0.736439       0.542873       1.065185       0.052\*              
  H19B   0.841615       0.429460       1.025572       0.052\*              
  ------ -------------- -------------- -------------- -------------------- ------------

Atomic displacement parameters (Å^2^) {#d1e1280}
=====================================

  ------ ------------- ------------- ------------- -------------- -------------- --------------
         *U*^11^       *U*^22^       *U*^33^       *U*^12^        *U*^13^        *U*^23^
  S1     0.0178 (2)    0.0277 (3)    0.0187 (2)    0.00755 (18)   0.00495 (16)   0.00898 (17)
  S2     0.0177 (2)    0.0326 (3)    0.0258 (2)    0.0071 (2)     0.00239 (17)   0.00938 (19)
  O1     0.0207 (6)    0.0323 (8)    0.0260 (7)    0.0062 (6)     0.0074 (5)     0.0127 (6)
  O2     0.0340 (7)    0.0270 (7)    0.0193 (6)    0.0155 (6)     0.0014 (5)     0.0059 (5)
  O3     0.0381 (8)    0.0300 (8)    0.0192 (6)    0.0180 (6)     −0.0001 (5)    0.0061 (6)
  O4     0.0537 (11)   0.0545 (11)   0.0353 (9)    −0.0034 (9)    0.0028 (8)     0.0182 (8)
  N1     0.0194 (7)    0.0214 (8)    0.0166 (7)    0.0071 (6)     0.0036 (5)     0.0057 (6)
  C1     0.0263 (9)    0.0293 (10)   0.0216 (9)    0.0131 (8)     0.0018 (7)     0.0066 (7)
  C2     0.0180 (9)    0.0275 (10)   0.0253 (9)    0.0076 (8)     0.0024 (7)     0.0034 (8)
  C3     0.0198 (9)    0.0225 (9)    0.0232 (9)    0.0078 (7)     0.0070 (7)     0.0066 (7)
  C4     0.0203 (8)    0.0209 (9)    0.0193 (8)    0.0099 (7)     0.0042 (7)     0.0031 (7)
  C5     0.0186 (8)    0.0215 (9)    0.0258 (9)    0.0070 (7)     0.0028 (7)     0.0050 (7)
  C6     0.0262 (9)    0.0234 (10)   0.0253 (9)    0.0099 (8)     0.0052 (7)     0.0090 (7)
  C7     0.0221 (9)    0.0193 (9)    0.0213 (9)    0.0071 (7)     0.0058 (7)     0.0060 (7)
  C8     0.0212 (9)    0.0176 (9)    0.0202 (8)    0.0066 (7)     0.0033 (7)     0.0034 (7)
  C9     0.0221 (9)    0.0326 (11)   0.0214 (9)    0.0123 (8)     0.0055 (7)     0.0100 (8)
  C10    0.0192 (8)    0.0191 (9)    0.0206 (8)    0.0059 (7)     0.0052 (7)     0.0047 (7)
  C11    0.0203 (9)    0.0189 (9)    0.0191 (8)    0.0062 (7)     0.0059 (7)     0.0047 (7)
  C12    0.0213 (9)    0.0203 (9)    0.0184 (8)    0.0073 (7)     0.0032 (7)     0.0035 (7)
  C13    0.0230 (9)    0.0201 (9)    0.0169 (8)    0.0085 (7)     0.0042 (7)     0.0038 (7)
  C14    0.0235 (9)    0.0240 (10)   0.0192 (8)    0.0099 (8)     0.0039 (7)     0.0086 (7)
  C15    0.0195 (8)    0.0255 (10)   0.0192 (8)    0.0080 (7)     0.0042 (7)     0.0086 (7)
  C16    0.0499 (15)   0.0590 (18)   0.0409 (14)   0.0004 (13)    0.0085 (12)    0.0025 (12)
  C17A   0.030 (3)     0.028 (3)     0.048 (3)     0.012 (2)      0.012 (2)      0.012 (2)
  C17B   0.062 (7)     0.034 (4)     0.054 (4)     −0.006 (3)     −0.012 (4)     0.014 (3)
  C18    0.0434 (13)   0.0515 (15)   0.0429 (13)   0.0158 (12)    0.0087 (10)    0.0195 (11)
  C19    0.0423 (13)   0.0387 (13)   0.0438 (13)   0.0125 (11)    −0.0052 (10)   0.0158 (10)
  ------ ------------- ------------- ------------- -------------- -------------- --------------

Geometric parameters (Å, º) {#d1e1743}
===========================

  ---------------------- -------------- ------------------------ --------------
  S1---C13               1.7485 (18)    C9---H9A                 0.9800
  S1---C11               1.7580 (18)    C9---H9B                 0.9800
  S2---C13               1.6391 (18)    C9---H9C                 0.9800
  O1---C12               1.211 (2)      C10---C11                1.350 (2)
  O2---C15               1.218 (2)      C10---H10                0.9500
  O3---C15               1.314 (2)      C11---C12                1.481 (2)
  O3---H3O               0.92 (3)       C14---C15                1.506 (2)
  O4---C16               1.401 (3)      C14---H14A               0.9900
  O4---C19               1.416 (3)      C14---H14B               0.9900
  N1---C13               1.368 (2)      C16---C17B               1.414 (8)
  N1---C12               1.400 (2)      C16---C17A               1.522 (7)
  N1---C14               1.455 (2)      C16---H23A               0.9900
  C1---C6                1.387 (3)      C16---H23B               0.9900
  C1---C2                1.389 (3)      C16---H23C               0.9900
  C1---H1                0.9500         C16---H23D               0.9900
  C2---C3                1.386 (3)      C17A---C18               1.492 (7)
  C2---H2                0.9500         C17A---H17A              0.9900
  C3---C4                1.402 (2)      C17A---H17B              0.9900
  C3---H3                0.9500         C17B---C18               1.549 (9)
  C4---C5                1.405 (3)      C17B---H17C              0.9900
  C4---C7                1.465 (2)      C17B---H17D              0.9900
  C5---C6                1.388 (3)      C18---C19                1.499 (3)
  C5---H5                0.9500         C18---H18A               0.9900
  C6---H6                0.9500         C18---H18B               0.9900
  C7---C8                1.357 (2)      C18---H18C               0.9900
  C7---H7                0.9500         C18---H18D               0.9900
  C8---C10               1.450 (2)      C19---H19A               0.9900
  C8---C9                1.504 (2)      C19---H19B               0.9900
                                                                 
  C13---S1---C11         92.63 (8)      C15---C14---H14A         109.5
  C15---O3---H3O         111.2 (18)     N1---C14---H14B          109.5
  C16---O4---C19         109.06 (19)    C15---C14---H14B         109.5
  C13---N1---C12         117.09 (14)    H14A---C14---H14B        108.1
  C13---N1---C14         122.23 (14)    O2---C15---O3            124.76 (17)
  C12---N1---C14         120.44 (14)    O2---C15---C14           122.99 (16)
  C6---C1---C2           119.91 (17)    O3---C15---C14           112.25 (15)
  C6---C1---H1           120.0          O4---C16---C17B          109.1 (4)
  C2---C1---H1           120.0          O4---C16---C17A          106.1 (3)
  C3---C2---C1           119.45 (17)    O4---C16---H23A          110.5
  C3---C2---H2           120.3          C17A---C16---H23A        110.5
  C1---C2---H2           120.3          O4---C16---H23B          110.5
  C2---C3---C4           121.68 (17)    C17A---C16---H23B        110.5
  C2---C3---H3           119.2          H23A---C16---H23B        108.7
  C4---C3---H3           119.2          O4---C16---H23C          109.9
  C3---C4---C5           117.91 (16)    C17B---C16---H23C        109.9
  C3---C4---C7           117.98 (16)    O4---C16---H23D          109.9
  C5---C4---C7           124.08 (16)    C17B---C16---H23D        109.9
  C6---C5---C4           120.33 (17)    H23C---C16---H23D        108.3
  C6---C5---H5           119.8          C18---C17A---C16         103.6 (4)
  C4---C5---H5           119.8          C18---C17A---H17A        111.0
  C1---C6---C5           120.68 (17)    C16---C17A---H17A        111.0
  C1---C6---H6           119.7          C18---C17A---H17B        111.0
  C5---C6---H6           119.7          C16---C17A---H17B        111.0
  C8---C7---C4           130.30 (16)    H17A---C17A---H17B       109.0
  C8---C7---H7           114.9          C16---C17B---C18         106.1 (6)
  C4---C7---H7           114.9          C16---C17B---H17C        110.5
  C7---C8---C10          116.00 (16)    C18---C17B---H17C        110.5
  C7---C8---C9           124.99 (16)    C16---C17B---H17D        110.5
  C10---C8---C9          118.99 (15)    C18---C17B---H17D        110.5
  C8---C9---H9A          109.5          H17C---C17B---H17D       108.7
  C8---C9---H9B          109.5          C17A---C18---C19         105.8 (3)
  H9A---C9---H9B         109.5          C19---C18---C17B         99.5 (4)
  C8---C9---H9C          109.5          C17A---C18---H18A        110.6
  H9A---C9---H9C         109.5          C19---C18---H18A         110.6
  H9B---C9---H9C         109.5          C17A---C18---H18B        110.6
  C11---C10---C8         130.49 (16)    C19---C18---H18B         110.6
  C11---C10---H10        114.8          H18A---C18---H18B        108.7
  C8---C10---H10         114.8          C19---C18---H18C         111.9
  C10---C11---C12        119.76 (16)    C17B---C18---H18C        111.9
  C10---C11---S1         130.59 (14)    C19---C18---H18D         111.9
  C12---C11---S1         109.55 (12)    C17B---C18---H18D        111.9
  O1---C12---N1          122.83 (16)    H18C---C18---H18D        109.6
  O1---C12---C11         127.15 (16)    O4---C19---C18           107.68 (19)
  N1---C12---C11         110.02 (14)    O4---C19---H19A          110.2
  N1---C13---S2          126.39 (13)    C18---C19---H19A         110.2
  N1---C13---S1          110.58 (12)    O4---C19---H19B          110.2
  S2---C13---S1          123.03 (11)    C18---C19---H19B         110.2
  N1---C14---C15         110.82 (14)    H19A---C19---H19B        108.5
  N1---C14---H14A        109.5                                   
                                                                 
  C6---C1---C2---C3      −0.1 (3)       S1---C11---C12---O1      −179.34 (16)
  C1---C2---C3---C4      −1.5 (3)       C10---C11---C12---N1     −175.57 (16)
  C2---C3---C4---C5      2.3 (3)        S1---C11---C12---N1      1.19 (18)
  C2---C3---C4---C7      −179.45 (16)   C12---N1---C13---S2      176.88 (13)
  C3---C4---C5---C6      −1.6 (3)       C14---N1---C13---S2      2.6 (2)
  C7---C4---C5---C6      −179.72 (16)   C12---N1---C13---S1      −3.58 (19)
  C2---C1---C6---C5      0.8 (3)        C14---N1---C13---S1      −177.86 (13)
  C4---C5---C6---C1      0.1 (3)        C11---S1---C13---N1      3.52 (13)
  C3---C4---C7---C8      153.36 (19)    C11---S1---C13---S2      −176.92 (12)
  C5---C4---C7---C8      −28.5 (3)      C13---N1---C14---C15     83.7 (2)
  C4---C7---C8---C10     178.50 (17)    C12---N1---C14---C15     −90.43 (19)
  C4---C7---C8---C9      −2.9 (3)       N1---C14---C15---O2      12.6 (2)
  C7---C8---C10---C11    −175.15 (18)   N1---C14---C15---O3      −167.93 (14)
  C9---C8---C10---C11    6.1 (3)        C19---O4---C16---C17B    −1.1 (9)
  C8---C10---C11---C12   178.17 (17)    C19---O4---C16---C17A    27.9 (4)
  C8---C10---C11---S1    2.2 (3)        O4---C16---C17A---C18    −26.5 (6)
  C13---S1---C11---C10   173.64 (18)    O4---C16---C17B---C18    18.8 (13)
  C13---S1---C11---C12   −2.65 (13)     C16---C17A---C18---C19   15.4 (6)
  C13---N1---C12---O1    −177.95 (16)   C16---C17B---C18---C19   −27.6 (12)
  C14---N1---C12---O1    −3.6 (3)       C16---O4---C19---C18     −17.9 (3)
  C13---N1---C12---C11   1.5 (2)        C17A---C18---C19---O4    0.3 (4)
  C14---N1---C12---C11   175.94 (14)    C17B---C18---C19---O4    27.2 (7)
  C10---C11---C12---O1   3.9 (3)                                 
  ---------------------- -------------- ------------------------ --------------

Hydrogen-bond geometry (Å, º) {#d1e2728}
=============================

  -------------------- ---------- ---------- ------------- ---------------
  *D*---H···*A*        *D*---H    H···*A*    *D*···*A*     *D*---H···*A*
  O3---H3*O*···O2^i^   0.92 (3)   1.73 (3)   2.6440 (18)   175 (3)
  C14---H14*B*···O4    0.99       2.26       3.127 (2)     145
  C2---H2···O1^ii^     0.95       2.51       3.389 (2)     154
  -------------------- ---------- ---------- ------------- ---------------

Symmetry codes: (i) −*x*+2, −*y*+2, −*z*+2; (ii) −*x*, −*y*+1, −*z*+1.

![The mol­ecular structure of the title compound, with the atom labelling and displacement ellipsoids drawn at the 50% probability level. The minor disorder component of the solvent molecule is not shown for clarity.](e-73-00941-fig1){#fig1}

![A view normal to (110) of the crystal structure of epalerstat tetra­hydro­furan monosolvate. Hydrogen bonds are shown as dashed lines (see Table 1[▸](#table1){ref-type="table"}) and only H atoms involved in these inter­actions have been included.](e-73-00941-fig2){#fig2}

![The TG--DSC scan of epalerstat tetra­hydro­furan monosolvate.](e-73-00941-fig3){#fig3}

![The PXRD--DSC scan of epalerstat tetra­hydro­furan monosolvate. The blue and red PXRD patterns represent the epalerstat tetra­hydro­furan monosolvate and epalerstat form II, respectively.](e-73-00941-fig4){#fig4}

###### Hydrogen-bond geometry (Å, °)

  *D*---H⋯*A*        *D*---H    H⋯*A*      *D*⋯*A*       *D*---H⋯*A*
  ------------------ ---------- ---------- ------------- -------------
  O3---H3*O*⋯O2^i^   0.92 (3)   1.73 (3)   2.6440 (18)   175 (3)
  C14---H14*B*⋯O4    0.99       2.26       3.127 (2)     145
  C2---H2⋯O1^ii^     0.95       2.51       3.389 (2)     154

Symmetry codes: (i) ; (ii) .

###### Experimental details

  -------------------------------------------------------------------------- ------------------------------------------------------------------------
  Crystal data                                                               
  Chemical formula                                                           C~15~H~13~NO~3~S~2~·C~4~H~8~O
  *M* ~r~                                                                    391.49
  Crystal system, space group                                                Triclinic, *P*
  Temperature (K)                                                            93
  *a*, *b*, *c* (Å)                                                          7.8956 (3), 8.9627 (3), 15.0311 (4)
  α, β, γ (°)                                                                102.263 (7), 93.970 (7), 114.219 (8)
  *V* (Å^3^)                                                                 933.23 (8)
  *Z*                                                                        2
  Radiation type                                                             Cu *K*α
  μ (mm^−1^)                                                                 2.80
  Crystal size (mm)                                                          0.44 × 0.33 × 0.12
                                                                             
  Data collection                                                            
  Diffractometer                                                             RIGAKU R-AXIS RAPID II
  Absorption correction                                                      Multi-scan (*ABSCOR*; Higashi, 1995[@bb7])
  *T* ~min~, *T* ~max~                                                       0.365, 0.721
  No. of measured, independent and observed \[*I* \> 2σ(*I*)\] reflections   10947, 3342, 3184
  *R* ~int~                                                                  0.029
  (sin θ/λ)~max~ (Å^−1^)                                                     0.602
                                                                             
  Refinement                                                                 
  *R*\[*F* ^2^ \> 2σ(*F* ^2^)\], *wR*(*F* ^2^), *S*                          0.036, 0.097, 1.03
  No. of reflections                                                         3342
  No. of parameters                                                          250
  H-atom treatment                                                           H atoms treated by a mixture of independent and constrained refinement
  Δρ~max~, Δρ~min~ (e Å^−3^)                                                 0.54, −0.41
  -------------------------------------------------------------------------- ------------------------------------------------------------------------

Computer programs: *PROCESS-AUTO* (Rigaku, 1998[@bb19]), *SHELXS2014* (Sheldrick, 2008[@bb20]), *Mercury* (Macrae *et al.*, 2008[@bb13]), *SHELXL2016* (Sheldrick, 2015[@bb21]), *PLATON* (Spek, 2009[@bb22]) and *publCIF* (Westrip, 2010[@bb24]).