WO2020117135A1

WO2020117135A1 - A process for preparation of 1h-pyrazolo[3,4-d] pyrimidine derivatives

Info

Publication number: WO2020117135A1
Application number: PCT/TR2018/050761
Authority: WO
Inventors: Philipp Daniel Haas; Andreas Hartwig STECKEL; Esen Bellur Atici; Ramazan ALTUNDAS; Busra OZTURK AYDIN; Hasan SECEN; Busra Nur AYDIN
Original assignee: Deva Holding Anonim Sirketi
Priority date: 2018-12-04
Filing date: 2018-12-04
Publication date: 2020-06-11

Abstract

The present invention relates to an efficient and industrially advantageous process for the preparation of 1H-pyrazolo[3,4-d] pyrimidine derivatives. In particular the present invention provides a process for the preparation of 4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4- d]pyrimidine and tert-butyl (R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4- d]pyrimidin-1-yl)piperidine-1-carboxylate. Said compounds are important intermediates in the synthesis of ibrutinib. The method provided for preparing intermediates of ibrutinib has the advantages of a simple operation, high yield and low costs.

Description

A PROCESS FOR PREPARATION OF lfl-PYRAZOLO[3,4-rf] PYRIMIDINE

DERIVATIVES

Technical Field

The present invention relates to a method for preparation of 3-(4-phenoxyphenyl)-lf/- pyrazoio[3,4-ii]pyrimidin-4-amine and /_{<? /7}-butyl (i?)-3-(4-amino-3-(4-phenoxyphenyl)-l//- pyrazolo[3,4-i/]pyrimidin-l-yl)piperidine-l-carboxylate through Suzuki-Miyaura cross coupling comprising rGO-Ni@Pd used as catalyst. Said compounds are useful intermediates for the preparation of ibrutinib or its pharmaceutically acceptable salts thereof.

Background Art

Ibrutinib is chemically designated as l [(3i?)-3-[4 ammo-3-(4 phenoxyphenyl)-l/:f- pyrazolo[3,4-rf]pyrimidin-l -yljpiperidin-l-yi]prop-2-en-l-one and structurally represented as below.

Ibrutinib is the first in class of an oral Bruton’s Tyrosine Kinase (BTK) inhibitor for the treatment of Mantle Cell Lymphoma (MCL), Chronic Lymphocytic Leukemia (CLL), and Waldenstrom's macrogiobulinemia (WM). Ibrutinib is currently marketed in the United States and Europe under the trade name of Imhruvica® by Janssen Pharmaceuticals.

Literature reports several processes for the preparation of ibrutinib or derivatives thereof. Ibrutinib was first described in US patent 7514444. 3-(4-Phenoxyphenyl)-lii-pyrazolo[3,4- ]pyrimidin-4-amine (intermediate A) and ieri-butyl (A)-3-(4-amino-3-(4-phcnoxyphcnyl)- 1 //-pyrazolo[3,4-c/Jpyrimidin- 1 -yljpipcridinc- 1 - carboxylate (intermediate B), are the key intermediates in the preparation of ibrutinib. The intermediate compound A and intermediate compound B having the following structures:

A synthesis route involving 3-(4-phenoxyphenyl)-IiApyrazolo[3,4- (]pyrimidin-4-amine and /_{<? /}7-butyl (A)-3-(4-amino-3-(4-phcnoxyphcnyl)- 1 //-pyrazolo[3,4-c/Jpyri midin- 1 -yljpipcridinc- 1-carboxylate for preparation of ibrutinib is disclosed in US patent 7514444. The reaction steps outlined by the following scheme 1:

Scheme 1

Regarding to the ibrutinib process disclosed in US patent 7514444 4-amino-3-(4- phenoxyphenyl)-lH-pyrazoIo[3,4-d]pyrimidine is reacted with ieri-butyl 3- hydroxypiperidine-l-carboxylate and diisopropyl diazodicarboxylate to obtain intermediate under Mitsunobu reaction conditions by converting the hydroxy moiety of the /e/t-hutyl 3- hydroxypiperidine- 1 -carboxylate to a better leaving group, thereby allowing a substitution reaction. Further, it is converted to ibrutinib by deprotection of Boc group and acylation with acryloyl chloride. Literature also reports several processes for the preparation of 4-amino-3-(4- phenoxyphenyl)- l//-pyrazolo[3,4- i]pyrimidine and /_{<? /7}-butyl (R)-3-(4-amino-3-(4-phenoxyphenyl)-l//- pyrazolo[3,4-i/]pyrimidin-l-yl)piperidine-l-carboxylate as key intermediates in the ibrutinib synthesis.

US patent 7514444 discloses process for the preparation of 3-(4-phenoxyphenyl)-li/- pyrazolo[3,4-d]pyrimidine-4-amine (1 ) The process disclosed in the patent is outlined in scheme 2 and it involves four key steps: (a) isolation of the enol-intemediate (3) form the base mediated reaction of the acid chloride, generated from 4-phenoxybenzoic acid (2), with malononitrile; (b) trimethylsilyldiazomethane mediated methylation of the eno!-intermediate (3) to furnish (4); (c) condensation of (4) with hydrazine hydrate to afford the pyrazole (5); and (d) construction of the pyrimidine (1) by reacting (5) with formamide.

The above synthesis route requires the isolation of individual synthetic intermediates and a particularly laborious purification protocol for intermediate (4). The above process also requires the use of potentially hazardous and expensive trimethylsilyldiazomethane.

US7514444 patent also discloses a different route for the preparation of intermediate A as following:

Ra

Scheme 3 li7-Pyrazole[3,4-ii]pyrimidine-4-amme is treated with N-iodosuccmimide to give 3-iodo-l H- pyrazolo[3,4-d]pyrirnidin-4-amine. Metal catalyzed cross coupling reaction in 1 ,4-dioxane by microwave heating carried out by using 3-iodo-lii-pyrazolo[3,4- ]pyrimidin-4-amine and suitably substituted boronic acid. Palladium mediated cross-coupling of a suitably substituted boronic acid under basic conditions affords 3-(4-phenoxyphenyl)-lfl-pyrazolo[3,4- d 1 pyrimidine-4-amine.

Use of microwave technique like in US patent US7514444 reduces chemical reaction times from hours to minutes. However, the risks associated with the flammability of organic solvents in a microwave field and the requirement of systems for adequate temperature and pressure controls causing equipment costs were major concerns. Although the reaction rate is fast US7514444, the process involving microwave reaction technique is not much suitable for industrial production.

WO2014022390A1 reports that 4 - a m i n o p y r a zo 1 o [ 3 , 4 - _<7] p y ri m i d i n c as a starting material was iodinated to prepare intermediate 3-iodo- l /7-pyrazolo[ 3, 4-i/Jpyri midi n-4-aminc, which was then coupled with 4-phenoxybenzeneboronic acid via Suzuki reaction to yield 3 (4- phenoxyphenyl)-lif-pyrazolo[3,4- ]pyrimidine-4-amine. A large amount of expensive catalyst tetrakis(triphenylphospine)palladium (2.70 g, 2.3 mmol, 0.15 equiv.) is used in this synthesis route. Therefore, this route is not economically suitable for industrial production. Chinese patent application CN105399756 discloses a similar process for the preparation of 3- (4-phcnoxyphcnyl)- 1 //-pyrazolo[3,4-c/Jpyrimidin-4-aminc. The schematic representation of the process is depicted below.

3-Iodo- 1 //-pyrazolo[3,4-c/Jpyrimidin-4-aminc coupled with (4-phenoxyphenyl)boronic acid by using a palladium catalyst ([l,r-bis(diphenylphosphino)ferrocene]palladium(II) dichloride [Pd(dppf)Cl2]) in the presence of 1,4-dioxane and water. The reaction was sealed overnight at 140 °C. The yield of 3-(4-phenoxyphenyl)-l//-pyrazolo[3,4-_<i]pyrimidin-4-amine is about 40% after purification process. In view of cost, the process in CN105399756 patent to prepare key intermediate 3-(4-phcnoxyphcnyl)-l //-pyrazolo[3,4-c/Jpyri midin-4-aminc is not preferable due to low yield.

PCT publication, WO2012158795 reports a similar process to obtain intermediate compound B. The route for preparation of tert- butyl (7i)-3-(4-amino-3-(4-phcnoxyphcnyl)- 1 H- pyrazolo[3,4-i/]pyrimidin-l-yl)piperidine-l-carboxylate as shown in scheme 4.

Scheme 4

The process involves reaction of /_{<? /7}-butyl (i?)-3-[4-amino-3-iodo-17/-pyrazolo[3,4- i/]pyrimidin-l-yl]piperidine-l-carboxylate (compound 14) with (4-pheoxyphenyl)boronic acid (compound 15) under the Suzuki cross-coupling reaction to give ieri-butyl (i?)-3-(4-amino-3- (4-phenoxyphenyl)- 1 /7-pyrazolo[3,4-_<7]pynmidin- 1 -yl)pipcridinc- 1 -carboxylatc (compound 9). Then, the residue was purified on a silica gel column eluted with

dichloromethane/methanol. But, after purification step the yield is lower (about 64%).

The reason for lower yield of intermediate B may be use of a homogenous catalyst like Pd(dppf)Cl2 in Suzuki coupling reaction. It has been know that Pd(dppf)Cl2 as catalyst has homogenous nature. Its separation from the reaction medium is not simple and requires many purification steps resulting in yield loss. From industrial aspect, said process is not preferable due to the difficulty in treatment of the spent catalyst causing the recycling to be expensive.

Therefore, based on the drawbacks mentioned in all the prior arts, there still exists a need to develop an improved process for preparing key intermediates of ibrutinib and its pharmaceutically acceptable salts thereof. The said process should be simple, cost-effective and suitable for large scale industrial preparation of ibrutinib intermediates.

The increase of cost effective alternative preparation methods for intermediates of ibrutinib will also affect the cost of ibrutinib finished medicinal products. Thus, present invention providing cheap and high quality ibrutinib intermediates would be also helpful for patients to get access to affordable and cheap ibrutinib drug products.

Summary of the invention

This invention provides a novel process with lower cost for the preparation 4-amino-3-(4- phcnoxyphcnyl)-l //-pyrazolo[ 3, 4-c/J pyrimidine and /_{<? /7}-butyl (R)-3-(4-amino-3-(4- phcnoxyphcnyl)-l //-pyrazolo[3,4-c/Jpyrimidin-l -yl)pipcridinc-l -carboxylatc as key intermediates in the synthesis of ibrutinib or its pharmaceutically acceptable salts thereof. The present invention provides excellent yields and purity.

Technical Problem Active pharmaceutical ingredients (APIs) are individual components or mixture of

components that are used as a part of a finished pharmaceutical drug or medicinal product, where they provide the pharmacological activity.

Research and development projects in the pharmaceutical industry mainly aim to investigate different possible synthetic routes, key intermediates, reaction steps, polymorphism, impurity profile, particle size and shape to produce these APIs with higher efficiency and less initial investments.

Technical challenges involve a multitude of issues designed to improve yield, purity, stereo selectivity, process conditions (i.e., temperature and pressure), scalability, and production economics. Most APIs can be synthesized using any of several alternative pathways. By using various synthetic pathways, it is possible to lower the production costs and simplify the process; therefore it has paramount importance to choose the right one for the general efficiency and success of the operation.

In the pharmaceutical industry; one of the critical parameters in development of API is to decrease the number of steps in the synthetic route or to increase the yield of intermediates.

Increasing the yield of key intermediates for desired API product increases the production efficiency, thereby production cost is reduced.

Most industrial production of API takes place under catalytic conditions

The function of catalysis in industry is to contribute to the development of economic, ecologic, and safe processes.

The conventional multi-step syntheses in API manufacturing need purification steps after completion of each step of the process. Therefore, the yields are relatively low and the product costs are increasing.

On the other hand, synthetic processes with catalysts provide mild process conditions like lower reaction temperatures, highly desired transformations, less by-products and shorter reaction times.

Despite the existence of processes for the preparation of ibrutinib and its intermediates, there remains a need for providing novel processes that would decrease the consumption of time and temperature that would allow cost-effective manufacturing.

Solution to Problem

For deficiencies in the prior art synthesis, our inventors tried to explore the possibility of improving the yield and reducing the cost for manufacturing of ibrutinib intermediates.

Our inventors have now discovered a method for preparation of 3-(4-phcnoxyphcnyl)- 1 H- pyrazolo[3,4-i/]pyrimidin-4-amine and /_{<? /7}-butyl (A)-3-(4-amino-3-(4-phcnoxyphcnyl)-l 7- pyrazolo[3,4-i/]pyrimidin-l-yl)piperidine-l-carboxylate as intermediates in the ibrutinib synthesis. This new method obviates the use of high temperature and long reaction periods resulting in a process which substantially reduces the production cost of corresponding intermediate compounds.

Description of embodiments The present invention relates to a method for synthesis of key amine intermediates which are useful for the preparation of ibrutinib or its pharmaceutically acceptable salts. The structures of key intermediates are represented as following:

The intermediate compound A is defined as wherein the X group is hydrogen. The intermediate compound B is defined as wherein the X group is N -{tert- butoxycarbonyl)piperidine.

The new synthesis of key amine intermediates by means of a Suzuki-Miyaura cross-coupling reaction using a metal catalyst provides in high yield and pure intermediate compounds.

The new synthesis of key amine intermediates also provides a process which is suitable for large-scale commercial production.

A method for preparing amine intermediates as represented by compound of formula (I) is shown as below:

X group is as described above.

The method for preparing amine intermediates, which uses a small amount of a Pd-catalyst, and replaces iodine on the compound of formula (III) with boronic acid compound of formula (II) by adding base, after the coupling reaction, the intermediate compound of formula (I) is formed.

Wherein the base may be selected from primary, secondary and tertiary amines (for example, alkylamines, dialkylamines, trialkylamines) that can be cyclic or open are used as bases;

alkali and alkaline earth metal salts of aliphatic and/or aromatic carboxylic acids (for example, acetates, propionates or benzoates); carbonates of alkali and alkaline earth metals, bicarbonates, phosphates, hydrophosphates and/or hydroxides; metal alkoxides (especially alkaline and alkaline earth metal alkoxides such as sodium methoxide, sodium ethoxide, potassium methoxide, magnesium methoxide, calcium ethoxide, etc.). Preference is given to carbonates, hydroxides or phosphates of lithium, sodium, potassium, calcium, magnesium or cesium, in particular NaOH, KOH, K2CO3, NaiCCh and CS2CO3. Fluorides can also be added to the reaction mixture, for example CaF, NaF, KF, LiF, CsF, etc.

The molar ratio of the 4-phenoxybenzene boronic acid (II) to the compound of formula (III) is

1.0-3.0. The molar ratio of the 4-phenoxybenzene boronic acid (II) to the base is 0.1-1.5.

The molar ratio of the catalyst to 4-phenoxybenzene boronic acid (II) is 0.001-0.002. The solvent may be selected from tetrahydrofuran, dioxane, diethyl ether, diisopropyl ether, diglyme, methyl tert- butyl ether, methyl tertiary amyl ether, dimethyl ether, 2- methyltetrahydrofuran, acetonitrile, butyronitrile, toluene, xylene, anisole, ethyl acetate, isopropyl acetate, methanol, ethanol, propanol, butanol, ethylene glycol, N,N- dimethylacetamide (DMA), N,N-dimethylformamide (DMF), ¾0, N-methylpyrrolidone (NMP) and their mixtures.

An inert atmosphere, nitrogen or argon is used to prevent the destruction of the catalyst during the reaction. Preferably, economically more favorable nitrogen atmosphere is used. Suzuki-Miyaura cross-coupling reaction is carried out at a temperature of 25 °C to 200 °C.

The reaction is carried out under reflux for a period comprised between 1 hour and 7 days, advantageously about 5-18 hours.

The intermediate amine compounds are isolated from the reaction mixture according to conventional procedures and purified by column chromatography. Purities of amine intermediate compounds have adequate purity exceeding 90%.

The present invention has beneficial effects when compared to prior art.

One of the advantages of this new synthetic process is carrying out the reaction via Suzuki- Miyaura cross -coupling.

The advantages of the Suzuki-Miyaura cross-coupling reactions have been well known. The major advantages of this coupling reaction are low cost, relatively low toxicity, commercial availability of a large number of boronic acids, excellent functional group tolerance and good availability of diverse organoboron reagents that are stable in air.

The type of catalyst used in Suzuki-Miyaura cross -coupling reactions is effective on the efficiency of the process. The other advantage of this new synthesis is Suzuki coupling reaction of the present invention involves different catalyst namely Reduced Graphene Oxide Supported Nickel @ Palladium Core @ Shell Nanoparticles (rGO-Ni @ Pd Nanocatalyst) as different from the known catalysts used in Suzuki-Miyaura cross -coupling reactions. This new catalyst for carbon-carbon coupling reactions is very advantageous compared to homogeneous catalysts like PdCl₂(PPli₃)₂, Pd(PPli₂)₄, PdCl₂(dppf), PdC PhCN^. rGO-Ni @ Pd catalysts are able to perform Suzuki-Miyaura carbon-carbon coupling reactions in more specific conditions provide to the synergistic interactions of the Ni and Pd atoms (geometric and electronic) in the specific core @ shell structure. Graphene has a very large surface area due to its stratified structure. Due to this feature, it is used as the support material for the catalyst.

In addition, the core @ shell structure provides higher catalytic efficiency with the use of less Pd metal particles.

Whereas palladium-catalyzed reactions allow rapid access to a diverse range of compounds, they also present a problem in that the palladium can often be retained in the isolated desired products. This is an especially significant problem for the pharmaceutical industry since there is a low limit for heavy metal impurities allowed in the active pharmaceutical ingredients (API). The levels of palladium in APIs must be kept very low (typically 0.1-10 ppm) for the compounds to be used for medicinal products according to ICH Q3D guideline for elemental impurities.

Industrial catalysis is generally divided into two types, homogeneous and heterogeneous. Heterogeneous catalysis is where the catalyst and the reactants are in the different physical phases, while homogeneous is where both are in the same phase. Recovery of homogeneous catalysts from the reaction mixture is difficult and the catalyst cannot be readily recycled for the next round of the reaction as compared to the heterogeneous catalyst. The problem may be solved by using supported Pd-based rGO-Ni® Pd as a catalyst.

The use of rGO-Ni® Pd catalyst having heterogeneous nature provides and significantly reduces the Pd load in the isolated intermediate products, due to the ease with which the catalyst can be removed from the reaction medium by a simple filtration process.

After the reaction, inductively-coupled plasma mass spectrometry (ICP-MS) analyses performed for the solution and the recovered catalyst samples and no detectable amount of Pd was found in the solution samples. According to these results, the rGO-Ni® Pd catalyst stays stable in reaction mixture and catalyst does not cause any contamination in the products obtained.

The rGO-Ni® Pd catalyst is reusable. It can be used repeatedly without significant loss in initial performance until at least 5 cycles.

No decrease in the metal content in the rGO-Ni® Pd catalyst and the possibility of its repeated use leads to a reduction in the cost of the product obtained. This feature provides a great advantage especially for the synthesis of pharmaceutical raw materials like ibrutinib or its intermediates thereof. In the present invention by the use of rGO-Ni® Pd catalyst, the production cost for key intermediates of ibrutinib is reduced, thereby greatly reducing the production cost of ibrutinib drug substance.

EXAMPLES The following examples are used to further illustrate the method for preparation of 3-(4- phenoxyphenyl)-l//-pyrazolo[3,4-i/]pyrimidin-4-amine and tert- butyl (A)-3-(4-amino-3-(4- phenoxyphenyl)-l//-pyrazolo[3,4-i/]pyrimidin-l-yl)piperidine-l-carboxylate provided in the present invention, but not to limit it.

Example 1 Preparation of 3-(4-phenoxyphenyl)-l//-pyrazolo[3,4-rflpyrimidin-4-amine

(Intermediate A)

3-Iodo-l//-pyrazolo[3,4-i ]pyrimidin-4-amine (0.94 g, 3.6 mmol), K2CO3 (3 eq., 1.49 g, 10.8 mmol), 4-phenoxybenzene boronic acid (2 eq., 1.54 g, 7.2 mmol) and G-Ni/Pd catalyst (190 mg, 20 wt%, Ni/Pd = 3/2, Pd: 0.14 mmol) were dissolved in THF (100 mL) at N2 atmosphere. The resulting mixture was heated at reflux until completion of the reaction. The progress of the reaction was monitored by thin layer chromatography (TLC). Upon completion of reaction, the mixture was cooled to room temperature. The catalyst was filtered. The filtrate was extracted with ethyl acetate (3 x 100 mL) / H2O (100 mL). The organic layer was dried over anhydrous Na2S04, filtered and concentrated under reduced pressure. The title compound was obtained after purification by column chromatography (DCM/MeOH) as a white solid (0.787 g, 2.59 mmol, 72% yield). Rf = 0.2 (5% MeOH/DCM).

MS (HRMS (Cl, [M+l]⁺): Calculated for [CI₇HI₄N₅0⁺]: 304.1193, found: 304.1159. ^lH NMR (400 MHz, DMSO) d: 13.55 (s, 1 H), 8.20 (s, 1 H), 7.65 (d, / = 8.7 Hz, 2 H), 7.41 (t, / = 7.9 Hz, 2 H), 7.20 - 7.02 (m, 4 H).

1³C NMR (100 MHz, DMSO) d: 158.8, 157.7, 157.0, 156.5, 144.6, 130.7, 129.1, 124.5, 119.6,

97.6.

Example 2

Preparation of tert- butyl (/?)-3-(4-amino-3-(4-phenoxyphenyl)-l.ff-pyrazolo[3,4- rf]pyrimidin-l-yl)piperidine-l-carboxylate (intermediate B)

Teri-butyl (R)-3-(4-amino-3-iodo- 1 //-pyrazolo[3,4-c/Jpyrimidin- 1 -yl)pipcridinc- 1 -carboxylatc (5.2 g, 11.7 mmol), K2CO3 (3 eq., 4.85 g, 35.1 mmol), 4-phenoxybenzene boronic acid (2 eq., 5.00 g, 23.4 mmol) and G-Ni/Pd catalyst (780 mg, 15 wt%, Ni/Pd = 3/2) were dissolved in THF (500 mL) at N2 atmosphere. The resulting mixture was heated at reflux until completion of the reaction. The progress of the reaction was monitored by thin layer chromatography (TLC). Upon completion of reaction, the mixture was cooled to room temperature. The catalyst was filtered. The filtrate was extracted with ethyl acetate (3x300 mL) / ¾0 (300 mL). The organic layer was dried over anhydrous Na SCL, filtered and concentrated under reduced pressure. The title compound was obtained after purification by column chromatography (DCM/MeOH) as a white solid (4.27 g, 8.77 mmol, 75% yield). Rf = 0.4 (%100 EtOAc). MS (HRMS (Cl, [M+l]⁺): Calculated for [CirfLiNeC^]: 487.245, found 487.244 ^lH NMR (400 MHz, CDCI3) d: 8.34 (s, 1 H), 7.65 (d, / = 8.4 Hz, 2 H), 7.35 (t, / = 8.0 Hz, 2 H), 7.15-7.12, (m, 3 H), 7.16 (d, / = 8.0 Hz, 2 H), 4.90^1.8 l(m, 1 H), 4.36-4.19 (m, 1 H), 4.12-4.06 (m, 1 H), 3.50-3.34(m, 1 H), 2.86 (t, / = 10.8 Hz, 1 H), 2.31-2.16 (m, 2 H), 1.93- 1.88(m, 1 H), 1.72-1.67 (m, 1 H), 1.49 (s, 9 H). ¹³C NMR (100 MHz, CDCI3) d: 158.7, 158.4, 156.6, 155.8, 154.8, 154.4, 144.0, 130.2, 130.2,

128.1, 124.2, 119.7, 119.3, 98.7, 80.0, 53.1, 48.4, 43.5, 30.4, 28.6, 24.8.

Claims

1. A process for the preparation of amine intermediate of formula (I) useful in the

synthesis of ibmtinib;

wherein X group is hydrogen or N-(tert-butoxycarbonyl)piperidine; comprising treating the compound of formula (III),

II with compound of formula (II),

in the presence of G-Ni/Pd used as catalyst and a strong base in a solvent to obtain compound of formula (I). 2. The process according to claim 1, wherein the solvent is selected from the group consisting of tetrahydrofuran, dioxane, diethyl ether, diisopropyl ether, diglyme, methyl tert- butyl ether, methyl tertiary amyl ether, dimethyl ether,

2- methyltetrahydrofuran, acetonitrile, butyronitrile, toluene, xylene, anisole, ethyl acetate , isopropyl acetate, methanol, ethanol, propanol, butanol, ethylene glycol, N,N- dimethylacetamide (DMA), N,N-dimethylformamide (DMF), water, N- methylpyrrolidone (NMP) and their mixtures.

3. The process according to claim 1, wherein the base is selected from the group consisting of primary, secondary and tertiary amines, alkali and alkaline earth metal salts of aliphatic and / or aromatic carboxylic acids, carbonates of alkali and alkaline earth metals, bicarbonates, phosphates, hydrophosphates and / or hydroxides, metal alkoxides, hydroxides or phosphates of lithium, sodium, potassium, calcium, magnesium or cesium and fluorides.

4. The process according to claim 1, the molar ratio of the compound of formula (II) to the compound of formula (III) is 1.0-3.0.

5. The process according to claim 1, the molar ratio of the compound of formula (II) to the base is 0.1 -1.5.

6. The process according to claim 1, the molar ratio of the the catalyst to 4- phenoxybenzene boronic acid (II) is 0.001-0.002.

7. The process according to claim 1, the reaction is carried out a temperature ranging from 25 °C to 200 °C to yield the intermediate compound of formula (I).

8. The process according to claim 1, the reaction is carried out for a period ranging from 1 hour to 7 days to yield the intermediate compound of formula (I).