Journal: Molecules

Article Title: Structure Determination of Tegoprazan(( S )-4-((5,7-difluorochroman-4-yl)oxy)- N , N ,2-trimethyl-1 H -benzo[ d ]imidazole-6-formamide) Polymorphs A and B by Laboratory X-Ray Powder Diffraction

doi: 10.3390/molecules30071538

Figure Lengend Snippet: Difference in the position of the NH group of Tegoprazan due to tautomerization indicates the presence of two tautomeric isomers, and this structural difference can be confirmed. It is important to note that the atom labels for Tegoprazan follow IUPAC nomenclature, which differs from the labels used in NMR analysis and crystallographic analysis. The distinction in the NMR analysis is made to avoid confusion as the same numbering is used for both the benzimidazole and chromane moieties.

Article Snippet: Tegoprazan Polymorphs A and B were sourced from HK inno.N Corporation (Seoul, South Korea) and Anhui Haoyuan Pharmaceutical Co., Ltd. (Shanghai, China), respectively, and used without further modification.

Techniques:

Journal: Molecules

Article Title: Structure Determination of Tegoprazan(( S )-4-((5,7-difluorochroman-4-yl)oxy)- N , N ,2-trimethyl-1 H -benzo[ d ]imidazole-6-formamide) Polymorphs A and B by Laboratory X-Ray Powder Diffraction

doi: 10.3390/molecules30071538

Figure Lengend Snippet: Chart overlaying 1 H- 13 C HSQC and HMBC spectra of two tautomer mixtures of Tegoprazan measured in DMSO- d6 solution on a 400 MHz NMR instrument. Starting with 5.88 ppm of hydrogen and 141.80 ppm of carbon, the associated carbon and hydrogen were assigned. In the structure of Tegoprazan shown on the left, the curved arrows indicate the positions of carbons and hydrogens that exhibit long-range coupling, as observed through HMBC cross-peaks. Within the benzimidazole moiety, some hydrogens and carbons were identified based on their correlations, enabling partial assignment of the carbon signals. The cross-peaks enclosed in the red rounded rectangle correspond to the interactions between the hydrogen of the NH group and its associated carbons.

Article Snippet: Tegoprazan Polymorphs A and B were sourced from HK inno.N Corporation (Seoul, South Korea) and Anhui Haoyuan Pharmaceutical Co., Ltd. (Shanghai, China), respectively, and used without further modification.

Techniques:

Journal: Molecules

Article Title: Structure Determination of Tegoprazan(( S )-4-((5,7-difluorochroman-4-yl)oxy)- N , N ,2-trimethyl-1 H -benzo[ d ]imidazole-6-formamide) Polymorphs A and B by Laboratory X-Ray Powder Diffraction

doi: 10.3390/molecules30071538

Figure Lengend Snippet: A comparison of the assigned 13 C-NMR spectra of each tautomer to the solid-state 13 C-NMR spectra of Tegoprazan Polymorphs A and B is presented. The expanded spectral range is 120–156 ppm, and only the carbon of the benzimidazole skeleton appears in this region in the benzimidazole moiety. The top spectrum ( A ) represents the liquid-state 13 C-NMR spectrum of the tautomeric mixture of Tegoprazan. The second spectrum ( B ) from the top corresponds to the solid-state 13 C-NMR spectrum of Polymorph A, while the third spectrum ( C ) from the top represents the solid-state 13 C-NMR spectrum of Polymorph B. At the bottom, the spectrum ( d ) shows only the peaks corresponding to Tautomer 1, extracted from the top spectrum. Similarly, the second spectrum ( c ) from the bottom displays only the peaks corresponding to Tautomer 2, also extracted from the bottom spectrum. Spectra ( a ) and ( b ) provide expanded views of regions ( B ) and ( C ), respectively, for enhanced clarity.

Article Snippet: Tegoprazan Polymorphs A and B were sourced from HK inno.N Corporation (Seoul, South Korea) and Anhui Haoyuan Pharmaceutical Co., Ltd. (Shanghai, China), respectively, and used without further modification.

Techniques: Comparison

Journal: Molecules

Article Title: Structure Determination of Tegoprazan(( S )-4-((5,7-difluorochroman-4-yl)oxy)- N , N ,2-trimethyl-1 H -benzo[ d ]imidazole-6-formamide) Polymorphs A and B by Laboratory X-Ray Powder Diffraction

doi: 10.3390/molecules30071538

Figure Lengend Snippet: Overlay of the 44 conformers of Tegoprazan Tautomer 1 after energy minimization, using the Superimpose function in Maestro with the benzimidazole moiety fixed as the reference. ( a ) Superimposition of all 44 conformers. ( b ) Superimposition of the four lowest-energy conformers among the 44 conformers. The energy difference between the highest- and lowest-energy conformers among these four was 0.2 kcal/mol.

Article Snippet: Tegoprazan Polymorphs A and B were sourced from HK inno.N Corporation (Seoul, South Korea) and Anhui Haoyuan Pharmaceutical Co., Ltd. (Shanghai, China), respectively, and used without further modification.

Techniques:

Journal: Molecules

Article Title: Structure Determination of Tegoprazan(( S )-4-((5,7-difluorochroman-4-yl)oxy)- N , N ,2-trimethyl-1 H -benzo[ d ]imidazole-6-formamide) Polymorphs A and B by Laboratory X-Ray Powder Diffraction

doi: 10.3390/molecules30071538

Figure Lengend Snippet: Rietveld fit to the powder X-ray diffraction data ( a ) and the ellipsoid representation of the structures of Tegoprazan Polymorphs A and B ( b ). The atomic numbering in ( b ) is arbitrarily assigned for the convenience of the structural analysis and differs from the numbering based on IUPAC nomenclature or that was assigned in NMR structural analysis.

Article Snippet: Tegoprazan Polymorphs A and B were sourced from HK inno.N Corporation (Seoul, South Korea) and Anhui Haoyuan Pharmaceutical Co., Ltd. (Shanghai, China), respectively, and used without further modification.

Techniques:

Journal: Molecules

Article Title: Structure Determination of Tegoprazan(( S )-4-((5,7-difluorochroman-4-yl)oxy)- N , N ,2-trimethyl-1 H -benzo[ d ]imidazole-6-formamide) Polymorphs A and B by Laboratory X-Ray Powder Diffraction

doi: 10.3390/molecules30071538

Figure Lengend Snippet: Results of crystal structure determination of Polymorphs A and B of Tegoprazan via simulated annealing and Rietveld refinement.

Article Snippet: Tegoprazan Polymorphs A and B were sourced from HK inno.N Corporation (Seoul, South Korea) and Anhui Haoyuan Pharmaceutical Co., Ltd. (Shanghai, China), respectively, and used without further modification.

Techniques:

Journal: Molecules

Article Title: Structure Determination of Tegoprazan(( S )-4-((5,7-difluorochroman-4-yl)oxy)- N , N ,2-trimethyl-1 H -benzo[ d ]imidazole-6-formamide) Polymorphs A and B by Laboratory X-Ray Powder Diffraction

doi: 10.3390/molecules30071538

Figure Lengend Snippet: Structural representations of Tegoprazan Polymorphs A and B determined through simulated annealing and Rietveld refinement.

Article Snippet: Tegoprazan Polymorphs A and B were sourced from HK inno.N Corporation (Seoul, South Korea) and Anhui Haoyuan Pharmaceutical Co., Ltd. (Shanghai, China), respectively, and used without further modification.

Techniques:

Journal: Molecules

Article Title: Structure Determination of Tegoprazan(( S )-4-((5,7-difluorochroman-4-yl)oxy)- N , N ,2-trimethyl-1 H -benzo[ d ]imidazole-6-formamide) Polymorphs A and B by Laboratory X-Ray Powder Diffraction

doi: 10.3390/molecules30071538

Figure Lengend Snippet: Supramolecular features of Tegoprazan Polymorph A, highlighting hydrogen bonding and π-H interactions contributing to the crystal packing stability. Hydrogen-bonding network in Tegoprazan Polymorph A as determined by simulated annealing and Rietveld refinement: A projection onto the (101) plane ( a ) reveals alternating conformers connected by hydrogen bonds with distances of 1.757 Å and 2.034 Å in the indicated direction, forming three distinct strands with no bonding in the b-direction . A projection onto the (10-1) plane ( b ) illustrates π-H interactions stabilizing interlayer arrangements between adjacent layers. The centroid of the five-membered imidazole ring in the benzimidazole moiety is marked with a filled red circle.

Article Snippet: Tegoprazan Polymorphs A and B were sourced from HK inno.N Corporation (Seoul, South Korea) and Anhui Haoyuan Pharmaceutical Co., Ltd. (Shanghai, China), respectively, and used without further modification.

Techniques:

Journal: Molecules

Article Title: Structure Determination of Tegoprazan(( S )-4-((5,7-difluorochroman-4-yl)oxy)- N , N ,2-trimethyl-1 H -benzo[ d ]imidazole-6-formamide) Polymorphs A and B by Laboratory X-Ray Powder Diffraction

doi: 10.3390/molecules30071538

Figure Lengend Snippet: Supramolecular features of Tegoprazan Polymorph B, highlighting hydrogen bonding and π-π interactions contributing to the crystal packing stability. Hydrogen bonding and π-π interactions in Tegoprazan Polymorph B as determined by simulated annealing and Rietveld refinement: A projection onto the (10-1) plane ( a ) shows identical conformers linked by hydrogen bonds with distances of 1.839 Å and 2.026 Å in the indicated direction, forming three strands. The benzene rings of the Chromane moiety are stabilized by interactions at a centroid–centroid distance of 3.703 Å, slightly offsetting and contributing to bonding along the a-direction. A projection onto the (010) plane ( b ) reveals vertically aligned benzene rings positioned at interaction-favorable distances, suggesting stabilization through π-π interactions. The centroid of the benzene ring in the chromane moiety is marked with a filled red circle.

Article Snippet: Tegoprazan Polymorphs A and B were sourced from HK inno.N Corporation (Seoul, South Korea) and Anhui Haoyuan Pharmaceutical Co., Ltd. (Shanghai, China), respectively, and used without further modification.

Techniques:

Journal: Molecules

Article Title: Structure Determination of Tegoprazan(( S )-4-((5,7-difluorochroman-4-yl)oxy)- N , N ,2-trimethyl-1 H -benzo[ d ]imidazole-6-formamide) Polymorphs A and B by Laboratory X-Ray Powder Diffraction

doi: 10.3390/molecules30071538

Figure Lengend Snippet: Hydrogen-bond geometry of Tegoprazan phase B.

Article Snippet: Tegoprazan Polymorphs A and B were sourced from HK inno.N Corporation (Seoul, South Korea) and Anhui Haoyuan Pharmaceutical Co., Ltd. (Shanghai, China), respectively, and used without further modification.

Techniques: