EP4642771A1 - AMINE DERIVATIVES OF DIHYDRODIBENZO[b,f]OXEPINES AND METHOD OF PREPARATION THEREOF - Google Patents

AMINE DERIVATIVES OF DIHYDRODIBENZO[b,f]OXEPINES AND METHOD OF PREPARATION THEREOF

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Publication number
EP4642771A1
EP4642771A1 EP24717814.8A EP24717814A EP4642771A1 EP 4642771 A1 EP4642771 A1 EP 4642771A1 EP 24717814 A EP24717814 A EP 24717814A EP 4642771 A1 EP4642771 A1 EP 4642771A1
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EP
European Patent Office
Prior art keywords
oxepine
dihydrodibenzo
methoxy group
substituents
followed
Prior art date
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Pending
Application number
EP24717814.8A
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German (de)
French (fr)
Inventor
Hanna Krawczyk
Piotr Tobiasz
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Politechnika Warszawska
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Politechnika Warszawska
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Publication date
Application filed by Politechnika Warszawska filed Critical Politechnika Warszawska
Publication of EP4642771A1 publication Critical patent/EP4642771A1/en
Pending legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/91—Dibenzofurans; Hydrogenated dibenzofurans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
    • C07D313/02—Seven-membered rings
    • C07D313/06—Seven-membered rings condensed with carbocyclic rings or ring systems
    • C07D313/10—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with two six-membered rings
    • C07D313/14—[b,f]-condensed

Definitions

  • the subject matter of the invention are dihydrodibenzo[b,f]ox epine derivatives with an amine group having a general formula 1 and a method of preparation thereof, which may have a medical application as precursors of molecular switches or compounds that block polymerization/depolymerization of microtubules.
  • Seven-membered oxygen-containing heterocyclic compounds exhibit a broad spectrum of biological activity.
  • a dibenzo[6,/]oxepine skeleton which is a structural motif of numerous natural derivatives, is an important functional component of many medicinal substances [Kittakoop, P.; Nopichai, S.; Thongon, N.; Charoenchai, P.; Thebtaranonth, Y. Helv. Chim. Acta 2004, 87, 175.Tojo, E.; Dominguez, D.; Castedo, L. Phytochemistry 1991, 30, 1005],
  • Dibenzo[Z ⁇ /]oxepine derivatives are characterised by various valuable properties such as anticancer [D. Garbicz, P. Tobiasz, F. Borys, T. Pilzys, M. Marcinkowski, M. Poterala, H. Krawczyk, Biomed. Pharmacother . 2020, 723, 109781, doi: 10.1016/j.biopha.2019.109781], antihypotensive [R. Kiyama, T. Honma, K. Hayashi, M. Ogawa, M. Hara, M. Fujimoto, Y. Fujishita, J. Med. Chem. 1995, 35(14), 2728-2741, doi: 10.1021/jm00014a024], anti-inflammatory [Y.
  • Dibenzo[Z ⁇ /]oxepine derivatives such as bauhiniastatins 1-4 and pacharin, which are present in the natural environment, among others in plants from the genus Bauhinia. are known from the chemical literature, wherein the main source of them is the compassioninia purpurea.
  • Bauhiniastatin shows significant activity against P388 lymphocytic leukaemia cell lines [G. R. Pettit , A. Numata , C. Iwamoto , Y. Usami, T. Yamada, H. Ohishi, G. M. Cragg, J. Nat. Prod. 2006, 69 , 323-327], Bulbofyol B [B.
  • Bermoprofen (Dibenon®), which was developed at Dainippon Pharmaceutical in the 1980s as a non-steroidal anti-inflammatory drug having activity twice as potent as indomethacin. Bermoprofen inhibits prostaglandin synthesis and has a strong antipyretic action [R. Olivera, R .Sanmartin, F. Churruca, E. Dominguez, a review. Org. Prep, and Proced. Ini., 2004 36(4), 297-330],
  • Actively acting dihydrodibenzo[b,f]oxepin derivatives with an amine group may find application in medicine as precursors of molecular switches or compounds that block polymerization/depolymerization of microtubules, what may create new opportunities for the treatment of patients suffering from neoplastic disease. Therefore, the aim of the invention was to develop a selective method of preparation thereof.
  • the subject matter of the invention are amine derivatives of dihydrodibenzo[A,/]oxepine having a general formula 1 formula 1, where Ri, R2, R3 are independently hydrogen or methoxy group, wherein at least one of the Ri, R2, R3 substituents is a methoxy group.
  • the other substituents are hydrogen.
  • a method of preparation of amine derivatives of dihydrodibenzo[A,/]oxepine having the formula 1 according to the invention characterised in that a methoxynitrodibenzo[A,/]oxepine having a formula 2 formula 2, where Ri, R2, R3 are independently hydrogen or methoxy group, wherein at least one of the Ri, R2, R3 substituents is a methoxy group, is mixed with the catalyst in a molar ratio of 1 :4 in an organic solvent, a mixture is then heated at the boiling point of the solvent for 5 minutes, followed by adding dropwise a hydrazine monohydrate slowly to the reaction mixture and is stirred for further 30 minutes at the boiling point, the post-reaction mixture is then filtered and washed twice with ethanol, and the resulting filtrate is left at the temperature -15°C for 24 hours, followed by separation of the final product therefrom by means of filtration under reduced pressure.
  • ethanol ethoxynitrodibenzo[A,/]ox
  • hydrazine monohydrate is used in a molar ratio of 1 :3 with regard to methoxynitrodibenzo[A,/]oxepine.
  • the method according to the invention is carried out in the air.
  • Fig. 1. shows the amine derivative of dihydrodibenzo[Z ⁇ /]oxepine prepared according to embodiment 1.
  • Fig. 2 shows the amine derivative of dihydrodibenzo[Z ⁇ /]oxepine prepared according to embodiment 2.
  • Fig. 3 shows the amine derivative of dihydrodibenzo[Z ⁇ /]oxepine prepared according to embodiment 3.
  • a stirring element 1 mmol of 3-nitro-6-methoxydibenzo[Z> 1 /]oxepine and 4 mmol of Pd/C 10 wt. % were placed in a 25 ml double neck flask. The whole was provided with a reflux condenser and heated at the boiling point of a solvent. After heating to this temperature, 3 mmol of hydrazine monohydrate was slowly added dropwise into the system and followed by carrying out the reaction for further 30 minutes. After this time, the reaction mixture was filtered on celite, washed twice with 1 ml of ethanol. The filtrate was kept at the temperature -15°C for 24 h. The resulting precipitate was filtered under reduced pressure to prepare the pure compound (Fig. 1).
  • the yield of the reaction is 76%.
  • a stirring element 1 mmol of 3-methoxy-7-nitrodibenzo[A,/]oxepine and 4 mmol of Pd/C 10 wt. % were placed in a 25 ml double neck flask. The whole was provided with a reflux condenser and heated at the boiling point of a solvent. After heating to this temperature, followed by carrying out the reaction for further 30 minutes. After this time, the reaction mixture was filtered on celite, washed twice with 1 ml ethanol. The filtrate was kept at the temperature -15°C for 24 h. The resulting precipitate was filtered under reduced pressure to prepare the pure compound (Fig. 2).
  • a stirring element 1 mmol of I -methoxy-7-nitrodibenzo[A,/]ox epine and 4 mmol of Pd/C 10 wt. % were placed in a 25 ml double neck flask. The whole was provided with a reflux condenser and heated at the boiling point of a solvent. After heating to this temperature, 3 mmol of hydrazine monohydrate was slowly added dropwise into the system and followed by carrying out the reaction for further 30 minutes. After this time, the reaction mixture was filtered on celite, washed twice with 1 ml of ethanol. The filtrate was kept at the temperature -15°C for 24 h. The resulting precipitate was filtered under reduced pressure to prepare the pure compound (Fig. 3).

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

The subject matter of the invention are dihydrodibenzo[b,f]oxepine derivatives having a general formula (1) and a method of preparation thereof, characterised by the fact that methoxynitrodibenzo[b,ƒ]oxepine having a formula (2) is mixed with a catalyst in a molar ratio of 1:4 in an organic solvent, a mixture is then heated at the boiling point of the solvent for 5 minutes, followed by adding dropwise a hydrazine monohydrate slowly to the reaction mixture and is stirred for further 30 minutes at the boiling point, the post-reaction mixture is then filtered and washed twice with ethanol, and the resulting filtrate is left at the temperature -15°C for 24 hours, followed by separation of the final product therefrom by means of filtration under reduced pressure.

Description

Amine derivatives of dihydrodibenzo \b,f\ oxepines and method of preparation thereof
The subject matter of the invention are dihydrodibenzo[b,f]ox epine derivatives with an amine group having a general formula 1 and a method of preparation thereof, which may have a medical application as precursors of molecular switches or compounds that block polymerization/depolymerization of microtubules.
Seven-membered oxygen-containing heterocyclic compounds exhibit a broad spectrum of biological activity. In particular, a dibenzo[6,/]oxepine skeleton, which is a structural motif of numerous natural derivatives, is an important functional component of many medicinal substances [Kittakoop, P.; Nopichai, S.; Thongon, N.; Charoenchai, P.; Thebtaranonth, Y. Helv. Chim. Acta 2004, 87, 175.Tojo, E.; Dominguez, D.; Castedo, L. Phytochemistry 1991, 30, 1005],
Dibenzo[Z\/]oxepine derivatives are characterised by various valuable properties such as anticancer [D. Garbicz, P. Tobiasz, F. Borys, T. Pilzys, M. Marcinkowski, M. Poterala, H. Krawczyk, Biomed. Pharmacother . 2020, 723, 109781, doi: 10.1016/j.biopha.2019.109781], antihypotensive [R. Kiyama, T. Honma, K. Hayashi, M. Ogawa, M. Hara, M. Fujimoto, Y. Fujishita, J. Med. Chem. 1995, 35(14), 2728-2741, doi: 10.1021/jm00014a024], anti-inflammatory [Y. Nagai, A. Irie, H. Nakamura, K. Hino, H. Uno, H. Nishimura, J. Med. Chem. 1982, 25(9), 1065-1070, doi: 10.1021/jm00351a012], antidepressant [H. Ong, J. Profitt, V. Anderson, T. Spaulding, J. Wilker, H. Geyer, H. Kruse, J. Med. Chem. 1980, 23(5), 494-501, doi: 10.1021/jm00179a005], antiestrogenic [D. Acton, G. Hill, B. Tait, J. Med. Chem. 1983, 26(8), 1131-1137, doi: 10.1021/jm00362a009], antipsychotic [J. Fernandez, J. Alonso, J. Andres, J. Cid, A. Diaz, L. Iturrino, A. Trabanco, J. Med. Chem. 2005, -75(6), 1709-1712, doi: 10.1021/jm049632c], neuroprotective [K. Zimmermann, P. Waldmeier, W. Tatton, Pure Appl. Chem. 1999, 77(11), 2039- 2046, doi: 10.135 l/pacl99971112039], antianxiety [A. Trabanco, J. Alonso, J. Andres, J. Cid, J. Fernandez, L. Iturrino, A. Megens, Chem. Pharm. Bull. 2004, 52(2), 262-265, doi: 10.1248/cpb.52.262] and antimycobacterial properties [P. Teweesak, P. Thongaram, P. Kraikruan, A. Thanetchaiyakup, N. Chuanopparat, H. Hsieh, B. Uang, P. Ngernmeesri, J . Org. Chem. 2021, 56(2), 1955-1963, doi: 10.1021/acs.joc.0c02452],
Dibenzo[Z\/]oxepine derivatives, such as bauhiniastatins 1-4 and pacharin, which are present in the natural environment, among others in plants from the genus Bauhinia. are known from the chemical literature, wherein the main source of them is the Bauchinia purpurea. Bauhiniastatin shows significant activity against P388 lymphocytic leukaemia cell lines [G. R. Pettit , A. Numata , C. Iwamoto , Y. Usami, T. Yamada, H. Ohishi, G. M. Cragg, J. Nat. Prod. 2006, 69 , 323-327], Bulbofyol B [B. Wu, Faming Zhuanli Shengqing Gongkai Shomingshu, CN 1458155 A 20031126, 2003] and 9- nitrobenzo[Z>]naphtho[7,2-; ]oxepine [D. Garbicz, P. Tobiasz, F. Borys, T. Pilzys, M. Marcinkowski, M. Poterala, H. Krawczyk, Biomed. Pharmacother. 2020, 123, 109781, doi: 10.1016/j.biopha.2019.109781] inhibit the growth of human epithelial cancer cell lines (HeLa), and azepane ring-containing derivatives show a great inhibitory effect on the proliferation of MDA-MB-231 breast cancer cell line [M. Ansari, M. Hussain, A. Arun, B. Chakravarti, R. Konwar, K. Hajela, Eur. J. Med. Chem. 2015, 99, 113-124, doi: 10.1016/j.ejmech,2015.05.035],
Another dibenzo[A,/]oxepine derivative well known in the prior art is Bermoprofen (Dibenon®), which was developed at Dainippon Pharmaceutical in the 1980s as a non-steroidal anti-inflammatory drug having activity twice as potent as indomethacin. Bermoprofen inhibits prostaglandin synthesis and has a strong antipyretic action [R. Olivera, R .Sanmartin, F. Churruca, E. Dominguez, a review. Org. Prep, and Proced. Ini., 2004 36(4), 297-330],
Actively acting dihydrodibenzo[b,f]oxepin derivatives with an amine group may find application in medicine as precursors of molecular switches or compounds that block polymerization/depolymerization of microtubules, what may create new opportunities for the treatment of patients suffering from neoplastic disease. Therefore, the aim of the invention was to develop a selective method of preparation thereof.
In the course of the research work carried out by the Inventors of the solution, representing a continuation of experiments on methods of preparation of dibenzo[b,f]oxepin derivatives disclosed, inter alia, in PL238243B1, PL228768B1, PL239208B1 patents, it has unexpectedly turned out that new amine derivatives of dihydrodibenzo[Z\/]oxepin could be selectively, easily and efficiently prepared in a one- step reduction reaction using hydrazine monohydrate.
The subject matter of the invention are amine derivatives of dihydrodibenzo[A,/]oxepine having a general formula 1 formula 1, where Ri, R2, R3 are independently hydrogen or methoxy group, wherein at least one of the Ri, R2, R3 substituents is a methoxy group.
Preferably, if one of the Ri, R2, R3 substituents is a methoxy group, the other substituents are hydrogen.
Further subject matter of the invention is a method of preparation of amine derivatives of dihydrodibenzo[A,/]oxepine having the formula 1 according to the invention, characterised in that a methoxynitrodibenzo[A,/]oxepine having a formula 2 formula 2, where Ri, R2, R3 are independently hydrogen or methoxy group, wherein at least one of the Ri, R2, R3 substituents is a methoxy group, is mixed with the catalyst in a molar ratio of 1 :4 in an organic solvent, a mixture is then heated at the boiling point of the solvent for 5 minutes, followed by adding dropwise a hydrazine monohydrate slowly to the reaction mixture and is stirred for further 30 minutes at the boiling point, the post-reaction mixture is then filtered and washed twice with ethanol, and the resulting filtrate is left at the temperature -15°C for 24 hours, followed by separation of the final product therefrom by means of filtration under reduced pressure. Preferably, in the method according to the invention ethanol is used as the organic solvent. Preferably, the catalyst is Pd/C.
Preferably, in the method according to the invention hydrazine monohydrate is used in a molar ratio of 1 :3 with regard to methoxynitrodibenzo[A,/]oxepine.
Preferably, the method according to the invention is carried out in the air.
The advantage of the method according to the invention is that dihydrodibenzo[Z\/]oxepine derivatives can be obtained with good yield in the reaction of simultaneous reduction of the olefinic bond and the nitro group. The method according to the invention is carried out in one step and, by using a suitable solvent, catalyst and reactant for the catalytic system, the method of synthesis is efficient and highly selective. The subject matter of the invention is illustrated in the figures of the drawing, in which: Fig. 1. shows the amine derivative of dihydrodibenzo[Z\/]oxepine prepared according to embodiment 1.
Fig. 2 shows the amine derivative of dihydrodibenzo[Z\/]oxepine prepared according to embodiment 2.
Fig. 3 shows the amine derivative of dihydrodibenzo[Z\/]oxepine prepared according to embodiment 3.
The invention is illustrated by the following embodiments.
Example 1.
A stirring element, 1 mmol of 3-nitro-6-methoxydibenzo[Z>1/]oxepine and 4 mmol of Pd/C 10 wt. % were placed in a 25 ml double neck flask. The whole was provided with a reflux condenser and heated at the boiling point of a solvent. After heating to this temperature, 3 mmol of hydrazine monohydrate was slowly added dropwise into the system and followed by carrying out the reaction for further 30 minutes. After this time, the reaction mixture was filtered on celite, washed twice with 1 ml of ethanol. The filtrate was kept at the temperature -15°C for 24 h. The resulting precipitate was filtered under reduced pressure to prepare the pure compound (Fig. 1).
The yield of the reaction is 76%.
'H NMR (500 MHz, CDCh, 298K): 8 (ppm): 6.97 (1H, t, JHS,H7.9 = 8.5 Hz, H8), 6.86 (1H, d, JHI,H2 = 8 Hz, Hi), 6.77 (1H, dd, JH8,H9 = 1.5 Hz, H7), 6.75 (1H, dd, H9), 6.65 (1H, d, JH2,H4 = 2.5 Hz, H4), 6.37 (1H, dd, JHI,H2 = 8 Hz, H2), 3.88 (3H, s, OCH3), 3.59 (2H, br. s, NH2), 3.13-3.11 (2H, m, Hu), 3.02-2.99 (2H, m, Hio).
13C NMR (125 MHz, CDCh, 298K): 8 (ppm): 157.14, 151.43, 146.63, 145.51, 135.03, 131.33, 124.04, 121.25, 120.68, 111.02, 110.24, 108.13, 56.13, 30.54, 30.41.
HRMS (ESI): m/z calculated for C I5HI5NO2+H 242.11756, found: 242.11731. m.p. = 137°C.
Example 2.
A stirring element, 1 mmol of 3-methoxy-7-nitrodibenzo[A,/]oxepine and 4 mmol of Pd/C 10 wt. % were placed in a 25 ml double neck flask. The whole was provided with a reflux condenser and heated at the boiling point of a solvent. After heating to this temperature, followed by carrying out the reaction for further 30 minutes. After this time, the reaction mixture was filtered on celite, washed twice with 1 ml ethanol. The filtrate was kept at the temperature -15°C for 24 h. The resulting precipitate was filtered under reduced pressure to prepare the pure compound (Fig. 2).
The yield of the reaction is 69%.
XH NMR (500 MHz, CDCh, 298K): 8 (ppm): 7.00 (1H, d, JHI,H2 = 8.5 Hz, Hi), 6.89 (1H, d, JH8.H9 = 8 Hz, H9), 6.70 (1H, d, JH2,H4 = 2.5 Hz, H4), 6.59 (1H, dd, H2), 6.52 (1H, d, JH6,HS = 2.5 Hz, He), 6.38 (1H, dd, H8), 3.78 (3H, s, OCH3), 3.55 (2H, br. s, NH2), 3.04- 3.01 (2H, m, Hio), 3.00-2.97 (2H, m, Hu).
13C NMR (125 MHz, CDCh, 298K): 8 (ppm): 158.71, 157.42, 157.37, 145.68, 130.97, 130.74, 124.01, 121.66, 111.01, 109.92, 107.49, 106.19, 55.39, 30.87, 30.65.
HRMS (ESI): m/z calculated for C15H15NO2+H 242.11756, found: 242.11722. m.p. = 136°C.
Example 3.
A stirring element, 1 mmol of I -methoxy-7-nitrodibenzo[A,/]ox epine and 4 mmol of Pd/C 10 wt. % were placed in a 25 ml double neck flask. The whole was provided with a reflux condenser and heated at the boiling point of a solvent. After heating to this temperature, 3 mmol of hydrazine monohydrate was slowly added dropwise into the system and followed by carrying out the reaction for further 30 minutes. After this time, the reaction mixture was filtered on celite, washed twice with 1 ml of ethanol. The filtrate was kept at the temperature -15°C for 24 h. The resulting precipitate was filtered under reduced pressure to prepare the pure compound (Fig. 3).
The yield of the reaction is 66%.
'H NMR (500 MHz, CDCh, 298K): 8 (ppm): 7.10 (1H, t, JH3,H2,4 = 8.5 Hz, H2), 6.93 (1H, d, JH8,H9 = 8 Hz, H9), 6.82 (1H, dd, JH2,H4 = 1 Hz, H2), 6.62 (1H, dd, H4), 6.53 (1H, d, JH6,H8 = 2.5 Hz, H6), 6.39 (1H, dd, H8), 3.81 (3H, s, OCH3), 3.58 (2H, br. s, NH2), 3.03 (4H, s, Hio, Hu).
13C NMR (125 MHz, CDCh, 298K): 8 (ppm): 158.21, 158.17, 157.74, 145.67, 130.21, 126.60, 123.16, 120.61, 113.61, 111.15, 107.49, 105.73, 55.71, 28.97, 24.70.
HRMS (ESI): m/z calculated for C15H15NO2+H 242.11756, found: 242.11734 m.p. = 121°C.

Claims

Claims
1. Amine derivatives of dihydrodibenzo[Z\/]oxepine having a general formula 1 where Ri, R2, R3 are independently hydrogen or methoxy group, wherein at least one of the Ri, R2, R3 substituents is a methoxy group.
2. The derivative according to claim 1, characterised in that if one of the Ri, R2, R3 substituents is a methoxy group, the other substituents are hydrogen.
3. A method of preparation of new amine derivatives of dihydrodibenzo[Z /]oxepine having the general formula 1 as defined in claims 1-2, characterised in that a methoxynitrodibenzo[A,/]oxepine having a formula 2 where Ri, R2, R3 are independently hydrogen or methoxy group, wherein at least one of the Ri, R2, R3 substituents is a methoxy group, is mixed with a catalyst in a molar ratio of 1 :4 in an organic solvent, a mixture is then heated at the boiling point of the solvent for 5 minutes, followed by adding dropwise a hydrazine monohydrate slowly to the reaction mixture and is stirred for further 30 minutes at the boiling point, the post-reaction mixture is then filtered and washed twice with ethanol, and the resulting filtrate is left at the temperature -15°C for 24 hours, followed by separation of the final product therefrom by means of filtration under reduced pressure.
4. The method according to claim 3, characterised in that ethanol is used as the organic solvent.
5. The method according to claim 3, characterised in that the catalyst is Pd/C.
6. The method according to claim 3, characterised in that hydrazine monohydrate is used in a molar ratio of 1 :3 with regard to methoxynitrodibenzo[Z>!/]oxepine.
7. The method according to claim 3, characterised in that it is carried out in the air.
EP24717814.8A 2023-02-01 2024-02-01 AMINE DERIVATIVES OF DIHYDRODIBENZO[b,f]OXEPINES AND METHOD OF PREPARATION THEREOF Pending EP4642771A1 (en)

Applications Claiming Priority (2)

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PL443656A PL247188B1 (en) 2023-02-01 2023-02-01 Amine derivatives of dihydrodibenzo[b,f]oxepins and the method of obtaining them
PCT/PL2024/050007 WO2024162861A1 (en) 2023-02-01 2024-02-01 AMINE DERIVATIVES OF DIHYDRODIBENZO[b,ƒ]OXEPINES AND METHOD OF PREPARATION THEREOF

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PL228768B1 (en) * 2014-06-30 2018-05-30 Politechnika Warszawska Method for obtaining methoxy derivatives of dibenz[b,f] oxepin
PL234529B1 (en) * 2018-03-06 2020-03-31 Politechnika Krakowska Im Tadeusza Kosciuszki System for forcing air masses movement above open areas
PL239208B1 (en) * 2019-03-25 2021-11-15 Politechnika Warszawska Method of preparing dibenzo[b,f]oxepine derivatives
PL247703B1 (en) * 2022-05-20 2025-08-25 Politechnika Warszawska Fluorine derivatives of methoxydibenzo[b,f]oxepine and method of their preparation

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