SYNTHESIS PROCEDURE FOR SULFONATED TRIARYLMETHANE COMPOUNDS

Abstract

The present invention relates to a process for preparing a compound of formula (I) (see Formula), this process being characterized in that it comprises at least one oxidation step of the sulfonated triphenylmethane of formula (V) with a quinone selected from 1,4-benzoquinone, 1,2-benzoquinone, dialkyl(C1-C4) 1,4-benzoquinone, dialkyl(C1-C4) 1,2-benzoquinone, monoalkyl(C1-C4) 1,4-benzoquinone, monoalkyl(C1-C4) 1,2-benzoquinone. A novel crystalline form of Patent Blue, sodium salt.

Description

SYNTHESIS PROCEDURE FOR SULFONATED TRIARYLMETHANE COMPOUNDS Technical field The present invention relates to a new process for synthesizing compounds comprising a triarylmethane structure substituted with sulfonated groups, specifically a new process for synthesizing dyes from the family of sulfonated triarylmethane compounds, in particular patent blue. Prior art Patent Blue (4-[[4-(diethylamino)phenyl]-(4-diethylazanioylidenecyclohexa-2,5-dien-l-ylidene)methyl]-6-hydroxybenzene-1,3-disulfonate salt) is a dye comprising a triarylmethane structure that exists in two forms: the sodium salt [CAS 20262-76-4] and the calcium salt [CAS 3536-49-0]. This dye was first mentioned in 1897 by Ernst Erdmann and Hugo Erdmann, Justus Liebigs Annalen der Chemie, Vol. 294 (3), 376-392. In publications on the subject, there is sometimes some confusion between patent blue and isosulfan blue (sodium salt of 2-[[4-(diethylamino)phenyl]-(4-diethylazanioylidenecyclohexa-2,5-dien-l-ylidene)methyl]benzene-1,4-disulfonate, CAS 68238-36-8 and 748080-29-7), even though these molecules have different structures. Patent blue is commercially available, although products on the market are characterized by a high impurity content. Specifically, large quantities of monodistilled compound have been found that are difficult to separate from patent blue using conventional purification methods. These products also contain a significant amount of residual NaCl. Patent blue and isosulfan blue are biological tissue dyes used specifically as contrast agents for delineating lymphatic vessels and are particularly useful as cancer diagnostic agents. They are commonly used in a diagnostic procedure called sentinel lymph node mapping. This method complements lymphography to visualize the lymphatic system draining the injection area. One important application is locating sentinel lymph nodes in patients with breast cancer. Surgical removal of cancerous tissue is also performed using patent blue or isosulfan blue as a guide. Few authors have shown interest in the synthesis of Patent Blue since the 1897 publication by Ernst and Hugo Erdmann. Among these authors are Hagenbach, Revue des colorants bleus, Helvetica, volume 6, number 1, 1923, pages 134-186; and Paul Fritsch, Euric, volume 29, number 2, May-August 1896, pages 2290-2301. From the basic reactions described in these documents, a wide variety of dyes can be produced, specifically compounds characterized by a sulfonated triarylmethane structure. The documents US 1531507, US7534911, US8969616, WO2017118882, WO2017218764 and WO2018008040 expose different synthesis procedures for isosulfan blue. Most prior art synthetic methods for the manufacture of sulfonated triarylmethane dyes comprise a condensation step of a sulfonated benzaldehyde with N,N-diethylaniline, a step involving strong acids and leading to the formation of a leuco compound. This step is generally followed by an oxidation step with known oxidizing agents, some of which are considered hazardous (lead oxide, iron phthalocyanine, oxone), to effect the conversion to a triarylmethane dye. Document DE46384 describes a process for synthesizing sulfonated triarylmethane dyes by means of a procedure that uses sulfonation of a triarylmethane structure by treatment with fuming sulfonic acid, followed by oxidation with lead oxide in the presence of sulfuric acid. Neither the product nor its purity has been characterized. The substitutions made to the aromatic rings are unknown. The inventors of this application have found that treatment with fuming sulfonic acid (gas SO3 at saturation in a concentrated H2SO4 solution) degrades the triarylmethane structure very rapidly. The conditions described in this document therefore do not allow the formation of the desired structure with satisfactory yields and purity. The paper AM Montagut et al., Chem. Eur. J. 2017, 23, 3810-3814, describes a synthesis of hydrophobic triarylmethane compounds for textile treatment. After the formation of the triarylmethane structure substituted with long-chain groups, the final step involves oxidation with a quinone, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The corresponding structures are significantly different from conventional dye molecules such as patent blue or isosulfan blue, whose aryl rings are substituted with short-chain groups and bear sulfonated functionalities. Among the impurities formed during the synthesis of these dialkylaminotriarylmethylsulfonated compounds, dealkylated derivatives are particularly irritating. In the case of patent blue and isosulfan blue, the impurities are deethyl impurities. These molecules differ from the target molecules only in the absence of one or more alkyl (ethyl) groups on the nitrogen atoms. Because their structure is very similar to that of the target compounds, they are difficult to remove using conventional purification techniques. Document WO2017 / 118882 claims the synthesis of isosulfan blue with a purity > 99.8% and a distillate impurity content < 0.15%. However, the described process involves an oxidation step with potassium permanganate, which can lead to manganese contamination. This method, when applied to the synthesis of patent blue, yields a compound with a much higher desethyl content. Document RU 2654862 describes a purification process for disulfonated diaminotriphenylmethane color compounds. This process specifically relates to Patent Blue. The process described herein is based on adsorption onto a PDMS support and recovery of Patent Blue using an aqueous saline solution. The product obtained from this process has a high salt content. The document Journal of Chromatography A 1499 (2017) 183-189 describes an electromagnetic separation procedure applied to color compounds, specifically Patent Blue. The operation is performed with respect to a mixture comprising two other dyes of different structures. The procedure is not intended for the removal of the distillate compound or other compounds of analogous structure. Therefore, the need remains for a synthetic process for sulfonated triarylmethane compounds that yields patent blue, as well as other structures such as isosulfan blue. Specifically, the aim has been to develop a reproducible, industrially applicable process with good yields that produces high-purity products. In particular, there is a continued need for a process that produces a composition in which the target compound is substantially free of dealkylated derivatives, particularly dedistilled derivatives in the case of patent blue and isosulfan blue, and that does not require the use of heavy metals. There is also a continued need for a method of preparing patent blue that leads to a product substantially free of salts. Surprisingly, the applicant has discovered a process that allows access to sulfonated triarylmethane compounds from simple and readily available molecules through a quinone oxidation step, achieving high yields and purity. The process of the invention yields products with satisfactory organic purity and purity with respect to heavy metals, while also providing good yields. Summary of the invention The invention relates to a process for preparing a compound that conforms to formula (I) R5 ηζαζ ιη / ζζηζ / Β / γίΛΐ in which R1, R2, R3 independently represent a group selected from: -H, -OH, -SO3H, -SOa-, at least one of R1, R2, R3 represents a group selected from (-SO3H, -SO3-) , R4, R5, identical or different, represent a group selected from: Ci-Cs alkyl, Ci-Cs alkenyl, phenyl, benzyl, it being understood that two R4, R5 groups on the same nitrogen atom can together form a ring that includes this nitrogen atom, And it represents an organic or inorganic cation selected from pharmaceutically acceptable salts; t represents a number t = 0; 1 / 2; 1, this process being characterized in that it comprises at least one oxidation step of the sulfonated triphenylmethane of formula (V) with a quinone selected from 1,4-benzoquinone, 1,2-benzoquinone, dialkyl(C1-C4) 1,4-benzoquinone, dialkyl (C1-C4) 1,2-benzoquinone, monoalkyl (C1-C4) 1,4-benzoquinone, monoalkyl (C1-C4) 1,2-benzoquinone: ηζαζ ιη / ζζηζ / Β / γίΛΐ is 1,4-benzoquinone. According to a preferred embodiment, the treatment is carried out in a nonpolar protic solvent. According to a preferred embodiment, the treatment is carried out at a temperature ranging from 40 to 130 °C, advantageously at a temperature ranging from 60 to 120 °C, and even more advantageously at a temperature ranging from 70 to 110 °C. According to a preferred embodiment, at the end of the treatment step with a quinone, the target compound of formula (I) is separated from the reaction medium by precipitation. According to a preferred embodiment, the process further comprises a step in which the target compound of formula (I) with t = 0 is transformed into the salt of formula (I) with t = 1 or t = 1 / 2. According to a preferred embodiment, the compound of formula (I) corresponds to formula (IA) nzaz Ln / zznz / e / γΐΛΐ According to a preferred embodiment, compound (IA) is obtained by a process comprising at least the following steps: a) condensation of the benzaldehyde compound of formula (IIA) with the dialkylaniline of formula (III) to give the triphenylmethane of formula (IVA), R4 NI R5 b) treatment of triphenylmethane of formula (IVA) with sulfuric acid to form sulfonated triphenylmethane of formula (VA) (VA) nzaz Ln / zznz / e / γΐΛΐ (IVA) According to a more preferred realization. The compound that corresponds to formula (I) is selected from: (VI) Patent blue, sodium salt (VII) Ca2' Patent blue, calcium salt (X) CH3 07Q71 η / 77Π7 Ε / ΥΙΛΙ patent blue, salt According to another variant, the compound that corresponds to formula (I) corresponds to formula (IB) OK of this the compound that corresponds to the formula (I) compound (VIII) CH isosulfan blue The invention further relates to the use of the procedure as described above and as described in more detail below, to obtain a composition comprising at least 99.0% of the compound corresponding to formula (I), the % having been measured by high-performance liquid chromatography (HPLC) with detection at 230 nm. According to a preferred embodiment, the use is intended to produce a composition in which no impurities other than the monodealkylated derivative are present in an amount greater than 0.1%, the % having been measured by high-performance liquid chromatography with detection at 230 nm. The invention further relates to a process for manufacturing a medicament or a diagnostic product comprising manufacturing the compound corresponding to formula (I), preferably patent blue, by the process as described above and as described in more detail below, and introducing the compound corresponding to formula (I) into a pharmaceutically acceptable vehicle. The invention allows obtaining a composition comprising at least 99.0% of the compound corresponding to formula (VI) or formula (VII) or formula (X), the % having been measured by high-performance liquid chromatography with detection at 230 nm: (VI) HO NaO,S-^ 12 OlOl γ so, ηζαζ Ln / zznz / e / γΐΛΐ patent blue, (VII) Ca2' patent blue, (X) HO KO3S' patent blue, HjC sodium salt 0 - ^X / ^ XXXX J' O3S so3 N H3CU J 2 calcium salt. ΪΙ 0 X .zs. χχχχ and η3ο^ potassium salt Advantageously, this composition contains no impurities other than the monodealkylated derivative in an amount greater than 0.1%, the percentage of which was measured by high-performance liquid chromatography with detection at 230 nm. The process of the invention has the advantage of yielding a composition substantially free of NaCl, preferably completely free of residual NaCl. The invention further relates to a crystalline form of the patent blue compound, sodium salt, which corresponds to formula (VI), characterized by the following powder X-ray diffraction pattern, measured on a diffractometer and expressed in terms of the inter-lattice distances d, the Bragg angle 2-theta, the intensity and the relative intensity (expressed as a percentage with respect to the most intense line): Angle 2-theta (°) Interlattice distance d (A) I (counts) I reí (%) 5.6 15.80 500 61.5 6.2 14.29 375 46.2 9.4 9.39 187.5 23.1 10.9 8.12 62.5 7.7 11.5 7.71 125 15.4 12.1 7.33 156.25 19.2 14.4 6.14 343.75 42.3 15.6 5.68 250 30.8 16.5 5.38 375 46.2 17.6 5.02 187.5 23.1 18.2 4.86 375 46.2 19.4 4.57 812.5 100.0 20.0 4.43 500 61.5 22.9 3.87 187.5 23.1 24.7 3.60 250 30.8 It is understood that the values ​​of the intensity (I) and the relative intensity (I reí) of the previous peaks may vary by + / - 15%. nzaz Ln / zznz / e / YiAi Advantageously, the crystal structure is substantially devoid of NaCl, preferably totally devoid of NaCl. The invention also relates to the crystalline form of the patent blue compound, sodium salt, for use as a medicament. In particular, it refers to the crystalline form of the patent blue compound, sodium salt, for use in diagnostics, as detailed in the following description. The invention further relates to a pharmaceutical composition comprising at least the crystalline form of the patent blue compound, sodium salt, which corresponds to formula (VI) as described above and as described in more detail below, in a pharmaceutically acceptable vehicle. Surprisingly, it has been found that the process of the invention allows for the direct production of a crystalline form of patent blue, specifically the sodium salt of patent blue, which was unknown in the prior art. The direct production of a crystalline form free of residual sodium chloride offers numerous advantages in terms of yield and purity, as well as efficiency and cost reduction for industrial-scale application of the process. The resulting product exhibits crystalline characteristics that confer good stability. The process of the invention facilitates manufacturing by reproducibly yielding a crystalline product with a unique polymorphism, which is required in most galenic formulations (particularly dry ones). The absence of NaCl enhances the solubility of patent blue in aqueous solution. Detailed description The expression essentially consists of one or more features, meaning that they may be included in the procedure or material of the invention, in addition to the explicitly listed compounds or steps, compounds or steps that do not significantly modify the properties and characteristics of the invention. The expression "between X and Y" includes the endpoints, unless explicitly stated otherwise. This expression therefore means that the interval in question comprises the values ​​X, Y, and any value between X and Y. Compounds obtained by the process of the invention The present invention relates to a process for obtaining compounds that correspond to the following formula (I): (I) ηζοζ ιη / ζζηζ / Β / γίΛΐ R5 in which R1, R2, R3 independently represent a group selected from: -H, -OH, -SO3H, -SCly, R4, R5, identical or different, represent a group selected from: Ci-Cs alkyl, Ci-Cs alkenyl, phenyl, benzyl, and two R4, R5 groups on the same nitrogen atom can together form a ring that includes this nitrogen atom, And it represents an organic or inorganic cation selected from pharmaceutically acceptable salts; t represents a number t = 0; 1 / 2; 1; At least one of R1, R2, R3 represents a group selected from -SO3H, -SOs-. Preferably, at least two of the groups R1, R2, R3 are selected from -SO3H, -SO3“. Advantageously, in formula (I) two of the groups R1, R2, R3 are selected from -SO3H, -SO3“ and the third group is different from -SO3H, -SO3“. Preferably, in formula (I): Rl = -SO3H or -SO3-; R2 = H; R3 = -SO3H or -SO3o Rl = -SO3H or -SO3-; R2 = -SO3H or -SO3-; R3 = -OH. More preferably, in formula (I): Rl = -SO3H or -SO3“; R2 = -SO3H or -SO3-; R3 = -OH. When two R4, R5 groups on the same nitrogen atom form a ring together, these groups can consist of a single alkyl or alkenyl chain forming a ring that includes the nitrogen atom. Advantageously, R4, R5, identical or different, represent a group selected from: Ci-Ce alkyl, phenyl, benzyl, and two R4, R5 groups on the same nitrogen atom can together form a chain -(CHz)p-, with p being an integer, p = 2 to 5. Even more advantageously, R4, R5, whether identical or different, represent a group selected from: C1-C3 alkyl, preferably from methyl and ethyl. Preferably, (R4; R5) is selected from (CH3; CH3), (C2H5; C2H5), (CH3; C2H5). According to a preferred embodiment, R4 = R5. Even more advantageously, (R4; R5) is selected from (CH3; CH3) and (C2H5; C2H5). According to a preferred variant, (R4; R5) represents (C2H5; C2H5). Advantageously, pharmaceutically acceptable salts refer to non-toxic salts in which the cation is selected from alkali metal ions, alkaline earth metal ions, or an ammonium ion. Even more advantageously, Y represents a group selected from: Na+, Ca2+, K+, Mg2+, or an ammonium group. Even more preferentially, Y represents a group selected from: Na+, Ca2+. According to a preferred variant, the process of the invention relates to obtaining compounds that correspond to the following formula (IA): (IA) where R4, R5, Y and t have the same definition as in formula (I). The preferences expressed above for the selection of these variables in the context of formula (I) also apply to formula (IA). In particular, the invention relates to the following compounds: ηζαζ ιη / ζζηζ / Β / γίΛΐ (X) Patent blue, calcium salt nzaz Ln / zznz / e / γΐΛΐ patent blue, potassium salt More preferably, the invention relates to patent blue, sodium salt and patent blue, calcium salt. Even more preferably, it refers to patent blue, sodium salt. Throughout the application, when patent blue is mentioned, it is understood to be a compound that corresponds to formula (VI), formula (VII) or formula (X). According to the procedure for obtaining compounds that correspond to the formula (IB) (IB) in which R5 And R4 that in formula (I). The rules for selecting these variables in the context of formula (I) also apply to formula (IB). In particular, the invention relates to the following compound: (VIII) isosulfan blue Throughout the application, whenever isosulfan blue is mentioned, it is understood to be a compound that corresponds to formula (VIII). Method for preparing a compound according to the invention - Stage c) of treatment with a quinone: The invention relates to a process for synthesizing a compound that corresponds to the formula (I) I R5 as defined above, being characterized in that it comprises at least one step c) of oxidation of the sulfonated triphenylmethane of formula (V) with a quinone selected from 1,4-benzoquinone, 1,2-benzoquinone, dialkyl(C1-C4) 1,4-benzoquinone, dialkyl(C1-C4) 1,2-benzoquinone, monoalkyl(C1-C4) 1,4-benzoquinone, monoalkyl(C1-C4) 1,2-benzoquinone following the scheme: nzaz Ln / zznz / e / γΐΛΐ (V) (I) In formula (V), the variables R1, R2, R3, R4, R5 have the same definition as in formula (I) (with the same preferred variants). During step c), the sulfonated triphenylmethane of formula (V) is oxidized to the target compound of formula (I) by treatment with a quinone. In this step, if high purity and high conversion yields are desired, it is important to avoid degradation of the triarylmethane structure and dealkylation, i.e., the substitution of one or more R4, R5 groups with hydrogen atoms. The quinone is selected from 1,4-benzoquinone, 1,2-benzoquinone, dialkyl(C1-C4) 1,4-benzoquinone, dialkyl(C1-C4) 1,2-benzoquinone, monoalkyl(C1-C4) 1,4-benzoquinone, monoalkyl(C1-C4) 1,2-benzoquinone. Dialkyl(C1-C4) 1,4-benzoquinone and dialkyl(C1C4) 1,2-benzoquinone mean a quinone having two identical or different, preferably identical, C1-C4 alkyl groups, such as, for example, 3,5-di-tert-butyl-1,2-benzoquinone or 2,5-dimethyl-1,4-benzoquinone. Monoalkyl(C1-C4) 1,4-benzoquinone and monoalkyl(C1-C4) 1,2-benzoquinone mean a quinone having one C1-C4 alkyl group, such as, for example, 2-methyl-1,4-benzoquinone. Preferably, the quinone is 1,4-benzoquinone. Surprisingly, these quinones have been found to give a high conversion rate and low degradation into desalkyl impurities, particularly deethyl impurities in the case of patent blue. Preferably, in step c), the treatment is carried out in a nonpolar protic solvent. For example, the solvent can be selected from dimethyl sulfoxide (DMSO), N-methylpyrrolidone (NMP), and dimethylformamide (DMF). Preferably, in step c), the treatment is carried out at a temperature ranging from 40 to 130 °C, advantageously at a temperature ranging from 60 to 120 °C, even more advantageously at a temperature ranging from 70 to 110 °C. Advantageously, at the end of step c), the target compound of formula (I) is separated from the reaction medium by precipitation. Preferably, this precipitation is induced by the addition of a solvent or a mixture of solvents selected from: alcohols, ethers, water, acetone, and mixtures thereof. Alternatively, the isolation of the compound of formula (I) from the reaction medium could be considered using other purification techniques such as solvent extraction or silica column chromatography. Stage d) of salification: nzaz Ln / zznz / e / YiAi When t is not equal to 0, the procedure comprises, after step c), a saltification step d). In a well-known manner, this step is carried out by introducing the target compound of formula (I) obtained in step c) (t = 0) into a solvent containing the selected counterion. In the specific case of patent blue, the counterion is advantageously selected from Na+ and Ca2+. Although derivatives of patent blue, corresponding to the target compound of formula (IA), can be obtained with another counterion Y by means of the process of the invention. Optionally, the procedure may be followed by one or more conventional purification steps such as precipitation, crystallization, solvent extraction, or chromatography. In the case of compound (IA), the combination of steps c) and d) can be summarized in the following scheme: (GOES) nzoz Ln / zznz / e / YiAi (IA) In the case of patent blue (sodium salt), the combination of steps o) and d) can be summarized in the following scheme: Surprisingly, it has been found that combining the two previous steps allows for the direct production of a crystalline form of patent blue, specifically the sodium salt of patent blue, which was unknown in the prior art. The direct production of a crystalline form offers numerous advantages in terms of yield and purity, as well as efficiency and cost reduction for industrial-scale application of the process. The resulting product exhibits crystalline characteristics that confer good stability. Obtaining the compound of formula (V) To carry out the procedure described above, a product of formula (V) is used which is oxidized with a quinone in step c). In certain cases, the product of formula (V) is commercially available, in which case the process of the invention comprises an oxidation step with a quinone and, optionally, a salification step. This is the case, for example, with isosulfan blue, whose precursor (IX) is commercially available: nzaz Ln / zznz / e / YiAi In other cases, the precursor of formula (V) is not available in sufficient quantity or of satisfactory quality, in which case it can be advantageously synthesized by a procedure such as described below. The preparation procedure for the compound of formula (V) advantageously comprises at least the following steps: a) condensation of the benzaldehyde compound of formula (II) with the dialkylaniline of formula (III) to give the triphenylmethane of formula (IV), nzaz Ln / zznz / e / γΐΛΐ R1, R2, R3 independently represent a group selected from: -H, -OH, and at least one of R1, R2, R3 represents H, R4, R5 have the same definition as in formula (I) - b) treatment of triphenylmethane of formula (IV) with sulfuric acid to form sulfonated triphenylmethane of formula (V) (V) In formula (V), the variables R1, R2, R3, R4, R5 have the same definition as in formula (I) (with the same preferred variants). The preferences expressed above for the selection of variables R4 and R5 in the context of formula (I) also apply to formulas (II), (III), (IV) and (V). The groups R1, R2, and R3 in formulas (II) and (IV) correspond either to R1, R2, and R3 as defined in formulas (I) and (V) or, for one or more of these groups, to a hydrogen atom that is replaced with an SOsH / SOa function during step b). Indeed, in step b), one or more hydrogen atoms are replaced between R1, R2, and R3 with an SOsH / SOs function. Stage a): Step a) consists of condensing the benzaldehyde compound of formula (II) with the dialkylaniline of formula (III) to give the triphenylmethane of formula (IV). Preferably, in formulas (II) and (IV), at least two of the groups R1, R2, R3 represent -H. Advantageously, two of the groups R1, R2, R3 are selected from H and the third is selected from -H and OH. Preferably in formulas (II) and (IV): R1 = R2 = H; R3 = -OH. Advantageously, in the preparation procedure defined above, step a) is carried out with 1.95 to 3 molar equivalents of dialkylaniline of formula (III) with respect to the amount of benzaldehyde of formula (II) · Advantageously, in the preparation procedure defined above, step a) is carried out in the presence of urea and in an acidic medium. Preferably, the reaction medium is acidified with hydrochloric acid. More advantageously, the reaction medium is acidified with 1.2 to 3 molar equivalents of hydrochloric acid relative to the amount of benzaldehyde of formula (II). Preferably, step a) is carried out in the presence of 0.25 to 1.5 molar equivalents of urea relative to the amount of benzaldehyde of formula (II). Advantageously, in the preparation procedure defined above, step a) is carried out in a solvent selected from protic solvents, particularly alcohols. Preferably, it is carried out in ethanol. Preferably, the ethanol is introduced into the reaction medium in an amount ranging from 1 to 6 volumes compared to the mass of aldehyde of formula (II). Advantageously, the reaction in step a) is carried out by heating to a temperature ranging from 60 °C to 120 °C for a period of 5 to 30 hours, even more advantageously at a temperature ranging from 75 °C to 100 °C for a period of 10 to 25 hours. Advantageously, at the end of the condensation reaction of step a), the reaction medium is treated to precipitate the compound of formula (IV). Preferably, this precipitation is induced by adding to the reaction medium a solvent selected from an acidic aqueous solution, acetone, or mixtures thereof. Advantageously, the compound of formula (IV) is isolated from the reaction medium by filtration and purified by washing. Advantageously, the washing is carried out with a solvent selected from an acidic aqueous solution, acetone, or mixtures thereof. Alternatively, the isolation of the compound of formula (IV) from the reaction medium could be considered using other purification techniques such as solvent extraction or chromatography, specifically nzoz Ln / zznz / e / YiAi silica column chromatography. In the case where compound (I) is compound (IA), step a) can be synthesized in the scheme In particular, in the case of patent blue (BP, bleu patenté), step a) can be summarized in the scheme Stage b): Advantageously, in the preparation procedure defined above, step b) is carried out by treatment with concentrated sulfuric acid. For example, a sulfuric acid solution of 90% or more by volume is used, preferably a sulfuric acid solution of 95% or more by volume. Preferably, the treatment comprises the addition of the compound of formula (IV) to 1 to 5 volumes of sulfuric acid. Advantageously, the solution of the compound of formula (IV) in sulfuric acid is brought to a temperature ranging from 60 to 120 °C for a period ranging from 30 min to 10 h, preferably to a temperature ranging from 80 to 100 °C for a period ranging from 1 to 5 h. Advantageously, at the end of step b), the sulfonated triphenylmethane of formula (V) is separated from the reaction medium by precipitation. Preferably, this precipitation is induced by the addition of a solvent or a mixture of solvents selected from: alcohols, ethers, water, acetone, and mixtures thereof; even more preferably, by the addition of alcohol (ethanol, isopropanol, ...), a water / alcohol mixture, a water / acetone mixture, or an alcohol / ether mixture (isopropanol / isopropyl ether, ethanol / isopropyl ether, ...). Alternatively, the isolation of the compound of formula (V) from the reaction medium could be considered using other purification techniques such as solvent extraction or chromatography, specifically silica column chromatography. Surprisingly, it has been found that, under the conditions described above, the sulfonation of the aromatic ring bearing the hydroxyl function in formula (IVa) occurs selectively at the ortho or para position of the ring when it comprises an -OH group in the meta position. In the case where compound (I) is compound (IA), step b) can be synthesized in the following scheme: ηζαζ ιη / ζζηζ / Β / γίΛΐ Step b), therefore, is particularly advantageous for the synthesis of compounds that conform to the formula (IA) defined above. Specifically, it allows obtaining patent blue with high selectivity for substitution of the ring bearing the sulfonated functional groups. On the other hand, contrary to what is observed under other sulfonation conditions, the above treatment leads to little formation of secondary products due to the degradation of the triarylmethane structure or the dealkylation of the alkylamine functions. In the case of patent blue, step b) can be summarized in the following scheme: Characteristics of the compounds obtained The process of the invention allows obtaining compositions comprising the target compound of formula (I), in particular compounds (IA) and (IB), more particularly compounds of formulas (VI), (VII), (X) and (VIII), with high yields and a very low impurity rate. In practice, the mono-dealkylated impurity (a single alkyl group among R4 and R5 is substituted with a hydrogen atom, and the other three are alkyl groups) is the main impurity observed during the synthesis of compounds of formula (I). Other dealkylated impurities with less similar structures have different properties and, if formed, are removed during the procedure. In particular, the procedure of the invention allows obtaining a composition comprising at least 98.0% of the compound corresponding to formula (I) and less than 1% of monodealkylated impurity (compound of formula (I) in which one of the groups R4 and R5 represents H), the % having been measured by high-performance liquid chromatography with detection at 230 nm. Even more preferably, the process of the invention allows obtaining a composition comprising at least 99.0% of the compound corresponding to formula (I) and less than 0.5% of monodealkylated impurity, with no other impurity present in an amount greater than 0.15%, the % having been measured by high-performance liquid chromatography with detection at 230 nm. In particular, the process of the invention allows obtaining a composition comprising at least 98.0% of the compound corresponding to formula (IA) or (IB) and less than 1% monodealkylated impurity (compound in which one of the groups R4 and R5 represents H), the percentage having been measured by high-performance liquid chromatography with detection at 230 nm. Even more preferably, the process of the invention allows obtaining a composition comprising at least 99.0% of the compound corresponding to formula (IA) or (IB) and less than 0.5% monodealkylated impurity, with no other impurity present in an amount greater than 0.15%, the percentage having been measured by high-performance liquid chromatography with detection at 230 nm. Advantageously, the procedure allows obtaining a composition in which there is no impurity present other than the monodealkylated derivative in an amount greater than 0.1%, having measured the % by high-performance liquid chromatography with a detection at 230 nm. In the case of patent blue, distillate-type impurities are represented by the following formulas in which Y and yt have the same definition as before (in particular Y = Na+yt = 1; Y = Ca2+yt = k; Y = K+yt = 1): Monodistilled impurity nzaz Ln / zznz / e / γΐΛΐ In practice, the mono-distilled impurity (a single ethyl group substituted with a hydrogen atom) is the main impurity observed during the synthesis of Patent Blue. Other dedistilled impurities with less similar structures have different properties and, if formed, are removed during the process. In particular, the process of the invention allows obtaining a composition comprising at least 98.0% of the salt compound 4-[[4-(diethylamino)phenyl]-(4-diethylazanioylidenecyclohexa-2,5-dien-l-l-idene)methyl]-6-hydroxybenzene-1,3-disulfonate) (patent blue) and less than 1% of monodesethyl impurity, the % having been measured by high-performance liquid chromatography with detection at 230 nm. Even more preferably, the process of the invention allows obtaining a composition comprising at least 99.0% of the salt compound of 4-[[4(diethylamino)phenyl]-(4-diethylazanioylidenecyclohexa-2,5dien-l-ylidene)methyl]-6-hydroxybenzene-l,3-disulfonate and less than 0.5% of monodesethyl impurity, no other impurity being present in an amount greater than 0.15%, the % having been measured by high-performance liquid chromatography with a detection at 230 nm. Advantageously, the procedure allows obtaining a composition in which there is no impurity present other than the monodestilled derivative in an amount greater than 0.1%, having measured the % by high-performance liquid chromatography with a detection at 230 nm. In particular, the process of the invention allows obtaining a composition comprising at least 98.0% of the sodium salt compound of 2-[[4-(diethylamino)phenyl]-(4-diethylazanioylidenecyclohexa-2,5-dien-lyliden)methyl]benzene-1,4-disulfonate) (isosulfan blue) and less than 1% of monodesethyl impurity, the % having been measured by high-performance liquid chromatography with a detection at 230 nm. Even more preferably, the process of the invention allows obtaining a composition comprising at least 99.0% of the sodium salt compound of N-[4-[[4(diethylamino)phenyl](2,5-disulfophenyl)methylene]-2,5cyclohexadien-l-ylidene)]-N-ethylethaneminium and less than 0.5% of monodesethyl impurity. Advantageously, the procedure of the invention allows obtaining a composition in which there is no impurity present other than the monodestilled derivative in an amount greater than 0.1%, having measured the % by high-performance liquid chromatography with a detection at 230 nm. The process of the invention also allows for obtaining compositions comprising a compound corresponding to formula (I), in particular compounds (IA) and (IB), and more specifically the compounds of formulas (VI), (VII), and (VIII), which comprise very little or no metallic impurities. It goes without saying that the salts of alkali and alkaline earth metals that may correspond to Y are not considered metallic impurities within the meaning of the invention. Specifically, the process of the invention allows obtaining compositions comprising a compound that corresponds to formula (I), in particular compounds (IA) and (IB), more particularly the compounds of formulas (VI), (VII) and (VIII), and comprising less than 200 ppm of metallic contaminants, advantageously less than 100 ppm of metallic contaminants, even better less than 50 ppm of metallic contaminants and, even more advantageously, less than 20 ppm of metallic contaminants. The metallic contaminant content refers to the metal content measured using the ICP / MS (Inductively Coupled Plasma Mass Spectrometry) method. Metallic contaminants are defined as all metals in the periodic table of elements, excluding alkali and alkaline earth metals, as well as their organic and inorganic derivatives. More specifically, metallic contaminants include the so-called heavy metals, and in particular: Al, As, Cd, Cr, Cu, Fe, Sn, Mn, Hg, Mo, Ni, Pb, Zn, as well as their organic and inorganic derivatives. The procedure of the invention also allows obtaining a crystalline form of patent blue, sodium salt, of formula (VI), characterized by the following powder X-ray diffraction pattern, measured in a diffractometer (copper anode) and expressed in terms of the inter-lattice distances d, the Bragg angle 2theta, the intensity and the relative intensity (expressed as a percentage with respect to the most intense line): nzaz Ln / zznz / e / γΐΛΐ Angle 2-theta (°) Interlattice distance d (A) I (counts) I reí (%) 5.6 15.80 500 61.5 6.2 14.29 375 46.2 9.4 9.39 187.5 23.1 10 . 9 8.12 62.5 7.7 11.5 7.71 125 15.4 12.1 7.33 156.25 19.2 14.4 6.14 343.75 42.3 15.6 5.68 250 30.8 16.5 5.38 375 46.2 17.6 5.02 187.5 23.1 18.2 4.86 375 46.2 19.4 4.57 812.5 100.0 20.0 4.43 500 61.5 22.9 3.87 187.5 23.1 24.7 3.60 250 30.8 It should be understood that the values ​​of intensity (I) and relative intensity (I reí) of the above peaks may vary by + / - 15% In the table above, all lines are assumed to be of order 1 (η = 1 in Bragg's law). Medicine: The invention also relates to a process for manufacturing a medicament or a diagnostic product comprising manufacturing the compound corresponding to formula (I), in particular compounds (IA) and (IB), more particularly the compounds of formulas (VI), (VII), (X) and (VIII), preferably patent blue, sodium salt, or isosulfan blue, by the process described above and introducing the compound corresponding to formula (I) into a pharmaceutically acceptable vehicle. The drug may be in any form suitable for use in the intended applications. In particular, the following may be mentioned: a tablet or capsule form comprising from 1 to 500 mg of the compound corresponding to formula (I), an aqueous solution form comprising the compound corresponding to formula (I), preferably patent blue or isosulfan blue, more preferably patent blue sodium salt, in a concentration ranging from 0.05% to 2% on a g / L basis. Specifically, a preferred formulation consists of an injectable aqueous solution. Such compositions comprise, in addition to the compound corresponding to formula (I), excipients well known to the skilled worker in the art such as, for example, citric acid and / or citrates, a phosphate buffer, polymers, cellulose derivatives or lipids. In medical applications, the compound corresponding to formula (I), preferably patent blue or isosulfan blue, even more preferably patent blue, when obtained by the process of the invention, has the advantage of high purity, thus avoiding the introduction into the body of materials that are not useful for the application. The efficiency of the inventive process allows access to a high-purity product at reduced costs, easily reproducible and applicable on an industrial scale. Furthermore, the inventive process yields a product with a crystalline structure, thus providing good stability. This composition is particularly interesting for use as a contrast agent for detecting lymphatic vessels and arterial regions and as a cancer diagnostic agent. Specifically, the composition of the invention can be used in a procedure called sentinel lymph node mapping. This procedure is particularly relevant to breast cancer, colon cancer, and melanoma. In particular, the composition is especially useful for sentinel lymph node detection before biopsy in patients with operable breast cancer and for preoperative sentinel lymph node mapping in patients with colon cancer. It is also used in preoperative lymphoscintigraphy for sentinel lymph node biopsy in melanoma. The different embodiments, variants, preferences, and advantages described above for each of the objects of the invention apply to all objects of the invention and may be considered separately or in combination. The invention is illustrated by the following examples, which are given without limitation. Figures Figure 1: Figure 1 is a graph representing the X-ray diffraction patterns of three samples of patent blue, sodium salt, obtained according to the procedure of the invention (designated as Inv 1, Inv 2, and Inv 3). These samples were obtained from three different production batches. On the abscissa: the angle 2-theta in degrees; on the ordinate: the intensity in arbitrary units of intensity. Figure 2: Figure 2 is a graph representing the X-ray diffraction patterns of six commercially available samples of patent blue, sodium salt (designated as C1 to C6). Also shown in this figure are the X-ray diffraction patterns of three samples of patent blue, sodium salt, obtained according to the procedure of the invention (designated as Inv1 to Inv3) and illustrated in Figure 1. On the abscissa: the angle 2-theta in degrees; on the ordinate: the intensity in arbitrary units of intensity. Examples: In these examples, parts and percentages are expressed by weight, unless otherwise stated. Materials and methods HPLC analysis: Column: AGILENT Poroshell 120 SB-C18 150 x 4.6 - 2.7 μ (Ref. 683975-902) Mobile phase A: Ammonium formate / formic acid buffer 10 mM (pH = 4.1 + 0.1) Mobile phase B: Acetonitrile Flow rate: 1 ml / min Temperature: 30 °C Injection volume: 5 μA Gradient: Analysis time of 40 min + 7 min stabilization after operation [Table 1] nzaz Ln / zznz / e / γΐΛΐ Time A % B % 0.0 90 10 4.0 90 10 12 85 15 30 10 90 40.0 10 90 40.1 90 10 47.0 90 10 ηζοζ ιη / ζζηζ / Β / γίΛΐ Detector: UV-VIS 230 nm and MS Electrospray (negative mode) Powder X-ray diffraction pattern: The powder X-ray diffraction pattern was obtained under the following experimental conditions: - X'Pert Pro MPD Panalytical Diffractometer (DY2764), Copper anode (A = 1.54 A), voltage: 40 kV, current: 40 mA - Θ-Θ Assembly - Measurement range: 2° to 50° - Increase between each measurement: 0.026° - Measurement time per step: 20.40 s, - PIXcel RTMS detector (PHD 25.5-7%, active length 3.347° Synthesis of patent blue (according to the invention): Step 1: Preparation of 3-(bis(4(diethylamino)phenyl)methyl)phenol hydrochloride: N,N-Diethylaniline (254.0 ml, 1.597 mol, 1.95 eq) is added to a mixture of 3-hydroxybenzaldehyde (100 g, 0.819 mol, 1.00 eq) and urea (24.6 g, 0.409 mol, 0.50 eq) in 100 ml of ethanol. The reaction medium is cooled to 0 °C and an aqueous solution of HC1 at 37% (136.5 ml, 1.638 mol, 2.00 eq) is poured in, keeping the medium at a temperature below 20 °C. Next, the reaction medium is heated under reflux for 20 h. The reaction medium is cooled to 60 °C and then 800 ml of an aqueous solution of 2 N HCl are poured in. The reaction medium is cooled to 0 °C and kept under agitation for 5 hours. The precipitate obtained is filtered and the solid is washed with 500 ml of a 2 N (9 / 1) aqueous acetone / HCl mixture and then with 500 ml of acetone. The solid is dried in a ventilated oven (50 °C). 303 g of 3-(bis(4(diethylamino)phenyl)methyl)phenol dichlorhydrate are obtained in the form of a white solid. HPLC purity: 97.2 % Yield: 78 % íH NMR (300 MHz, D20) : δ 7.39 (4H, dd, J=8.7 Hz), 7.33 (4H, dd, J=8.1 Hz), 7.22 (1H, t, J=1.9 Hz ), 6.80 (1H, ddd), (1H, dd, 16.1 Hz). J=7.8 Hz), 6.67 (1H, t, J=2.0 Hz), 5.67 (1H, s), 3.60 (8H, q, J=6.9 Hz), 1.06 (12H, t, J=7.2 Hz)13C NMR (75 MHz, D20) : δ6.5, 15.5. 144.3, 135.1, 131.2, 130.3, 122.4, 121.4, 116.2, 114.0, 54.9, 53.7, 9.7 Step 2 :Preparation of 4- (bis (4(diethylamino)phenyl)methyl)-6-hydroxybenzene-l,3-disulfonic acid: NOS Ln / zznz / e / γΐΛΐ 3-(bis(4(diethylamino)phenyl)methyl)phenol dichlorohydrate (150 g, 0.315 mol, 1 eq.) in 600 mi H2SO4 is added. It is heated at 90 °C for 3 hy then left for 16 h under stirring at room temperature. The reaction medium is diluted with 15 1 of an ethanol / isopropyl ether (75 / 25) mixture while maintaining a temperature below 20 °C. The precipitate obtained is filtered and the solid is washed with 2 x 600 ml of isopropyl ether. The solid is dried in a ventilated oven (50 °C). 183 g of 4-(bis(4(diethylamino)phenyl)methyl)-6-hydroxybenzene-l,3-disulfonic acid is obtained in the form of a white solid. HPLC purity: 98.8% Performance: quantitative2Η NMR (300 MHz, DMSO) : δ 10.91 (2H, sa), 8.08 (1H, s), 7.52 (4H, dd, J=8.5 Hz), 7.38 (4H, dd, <7=8.6 Hz), 6.95 (1H, s), 6.54 (1H, s), 4.75 (1H, sa ), 3.54 (8H, q, <7=7.1 Hz), 0.92 (12H, t, J=6.1 Hz)13C NMR (75 MHz, DMSO) : δ 153.6, 145.2, 143.0, 137.1, 135.5, 130.8, 128.0, 126.7, 122.3, 118.4, 52.5, 49.2, 10.1 Step 3: Preparation of the patent blue: ηζαζ ιη / ζζηζ / Β / γίΛΐ 4-(bis(4-(diethylamino)phenyl)methyl)-6-hydroxybenzene-1,3-disulfonic acid (1.2 kg, 2.1 mol, 1 eq.) is added to 6 1 of N-methylpyrrolidone. The reaction medium is heated to 95 °C and 1,4-benzoquinone (346 g, 3.2 mol, 1.5 eq.) is poured into solution in 1.2 1 of N-methylipyrrolidone. The heating is continued for 3 hours and then it is left to cool to room temperature. The reaction medium is diluted with 18 1 of acetone. The precipitate obtained is filtered and the solid is washed with 2x61 of acetone. The solid is collected in 6 1 of a HaO / methanol (80 / 20) mixture. It is heated to 1 h under reflux and then allowed to cool to room temperature. The solid is filtered and washed with 2 x 6 L of acetone. The solid is collected in 15 L of methanol under stirring and a 22% aqueous solution of sodium carbonate (256 ml) is added. It is left to agitate for 3 hours and then concentrated. It is collected in 10 1 of isopropanol. The solid is recovered by filtration and washed with 2x41 of acetone The solid is dried in a ventilated oven (50 °C). 766 g of the sodium salt of 4-[[4(diethylamino)phenyl]-(4-diethylazanioylidenecyclohexa-2,5dien-l-ylidene)methyl]-6-hydroxybenzene-l,3-disulfonate) (patent blue) is obtained in the form of a violet solid. HPLC purity: 99.3% Performance: 61% !H NMR (300 MHz, D2O) : δ 8.29 (1H, s), 7.24 (4H, dd, J-8.8 Hz), 6.72 (4H, dd, J-8.9 Hz), 6.41 (1H, s), 3.49 (8H, q, <7=5.8 Hz), 1.12 (12H, t, <7=5.9 Hz)13C NMR (75 MHz, D2O) : δ 170.1, 156.6, 154.9, 141.6, 139.7, 133.2, 128.9, 128.2, 125.6, 121.2, 113.5, 45.8, 12.2 Patent blue synthesis (comparative): The procedure was followed as described above for steps 1 and 2. For step 3, the protocol described above was followed, varying the oxidizing compound. This oxidizing compound could be another quinone or another oxidizing reagent. The results obtained are given in tables 2 and 3 below ηζαζ ιη / ζζηζ / Β / γίΛΐ [Table 2] Quinone Conversion rate stage 3 (*) Monodesethylated compound % (*) 1,4-benzoquinone (a) 93% <1% 3,5-di-tert-butyl-1,2benzoquinone (a) 93% 2.6% 2,5-dimethyl-l,4benzoquinone (a) 70% 1.7% 2-methyl-l,4-benzoquinone (a) 52% 2.1% 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (b) 31% 2.4% Tetrachloro-1,4benzoquinone (b) 90% 6.8% Tetrachloro-1,2benzoquinone (b) 65% 4% 2-chloro-1,4-benzoquinone (b) 92% 3.7% (*) measured according to the HPLC method described above nzaz Ln / zznz / e / YiAi (a) according to the invention (b) comparative It has been observed that certain quinones allow for high conversion rates while simultaneously yielding a product with low monodistilled impurities. Other quinones produce either very low yields or a very high content of monodistilled compound, which is difficult to separate. [Table 3] Oxidant (comparative) Conversion rate stage 3 (*) Monodistilled compound % U) KMnO4 95% 5% NaMnO1 78% 7% Cerium(IV) ammonium nitrate 41% 4% MnO2 3 8% 5% FeCl3 — — (*) measured according to the HPLC method described above It has been observed that only a few oxidizing reagents other than quinones can transform the compound of formula (V) into patent blue. Few of these reagents yield a desethyl content of less than 5% or achieve a low conversion rate. Furthermore, these reagents are based on heavy metals, the use of which is not recommended, both for environmental reasons and to avoid contamination of the final product. X-ray diffractogram of powder: The powder X-ray diffraction profile (diffraction angles) of patent blue, sodium salt, obtained in Example 3 is given by the significant lines in Table 4, along with their intensity and relative intensity (expressed as a percentage of the most intense line). The measurement was carried out on three different batches, all of which exhibit substantially the same profile as that shown in Figure 1. Batches Inv 1, Inv 2, and Inv 3 were prepared on a pilot scale (3 to 6 kg prepared). This measurement confirms that the crystalline characteristics of the product are constant at the end of the preparation procedure. It also confirms the absence of NaCl (see the characteristic peaks in Figure 2). Angle 2-theta (°) Interlattice distance d (A) I (counts) I reí (%) 5.6 15.80 500 61.5 6.2 14.29 375 46.2 9.4 9.39 187.5 23.1 10.9 8.12 62.5 7.7 11.5 7.71 125 15.4 12.1 7.33 156.25 19.2 14.4 6.14 343.75 42.3 15.6 5.68 250 30.8 16.5 5.38 375 46.2 17.6 5.02 187.5 23.1 18.2 4.86 375 46.2 19.4 4.57 812.5 100.0 20.0 4.43 500 61.5 22.9 3.87 187.5 23.1 24.7 3.60 250 30.8 Table 4 ηζαζ ιη / ζζηζ / Β / γίΛΐ Comparison with patent blue, sodium salt products, marketed: The commercial products of the following producers (Table 5) were analyzed using the same X-ray diffraction method: Producer Commercial Reference Reference in Figure 2 AGROS 339330050 C1 Santa Cruz Biotechnology SC250 653 C2 TCI A1242 C3 Combi Blocks HA8936 C4 Biosynth FC1571 C5 Colorey FG18191327 C6 Table 5: Patent Blue, sodium salt, marketed The results are shown in Figure 2. It is observed that most of the peaks do not correspond to those of the patent blue, sodium salt, of the invention, as shown in Table 4 and Figure 1. This observation allows us to conclude that the patent blue, sodium salt, of the invention is a novel crystalline form compared to known crystalline forms. Figure 2 also shows the presence of peaks characteristic of NaCl, specifically peaks at angles 2-theta = 32° and 45.5°, which confirms the presence of NaCl in all commercially available patent blue samples, but not in the patent blue, sodium salt, according to the invention. It is hereby stated that, as of this date, the best method known to the applicant for putting the aforementioned invention into practice is the one that is clear from the present description of the invention.

Claims

1. A method for preparing a compound that corresponds to the formula (I) nzaz Ln / zznz / e / YiAi R5 wherein R1, R2, R3 independently represent a group selected from: -H, -OH, -SO3H, -SOs”, at least one of R1, R2, R3 represents a group selected from (-SO3H, -SOs) , R4, R5, identical or different, represent a group selected from: Ci-Cs alkyl, Ci-Cs alkenyl, phenyl, benzyl, it being understood that two groups R4, R5 on the same nitrogen atom can together form a ring that includes this nitrogen atom, Y represents an organic or inorganic cation selected from pharmaceutically acceptable salts; t represents a number t = 0; 1 / 2;1, this process being characterized in that it comprises at least one oxidation step of the sulfonated triphenylmethane of formula (V) with a quinone selected from 1,4-benzoquinone, 1,2-benzoquinone, dialkyl(C1-C4) 1,4-benzoquinone, dialkyl(C1-C4) 1,2-benzoquinone, monoalkyl (C1-C4) 1,4-benzoquinone, monoalkyl (C1-C4) 1,2-benzoquinone: ηζαζ ιη / ζζηζ / Β / γίΛΐ (V) (I); 2. Process according to claim 1, wherein the quinone is 1,4-benzoquinone.

3. Process according to claim 1 or claim 2, wherein the treatment is carried out in a nonpolar protic solvent.

4. A method according to any one of claims 1 to 3, wherein the treatment is carried out at a temperature ranging from 40 to 130 °C, advantageously at a temperature ranging from 60 to 120 °C, and even more advantageously at a temperature ranging from 70 to 110 °C.

5. A process according to any one of claims 1 to 4, wherein, at the end of the treatment step with a quinone, the target compound of formula (I) is separated from the reaction medium by precipitation.

6. A process according to any one of claims 1 to 5, further comprising a step in which the target compound of formula (I) with t = 0 is transformed into the salt of formula (I) with t = 1 or t = 1 / 2.

7. A process according to any one of claims 1 to 6, wherein the compound corresponding to formula (I) corresponds to formula (IA). nzoz Ln / zznz / e / YiAi 8. A process according to claim 7, wherein compound (IA) is obtained by a process comprising at least the following steps: a) condensation of the benzaldehyde compound of formula (IIA) with the dialkylaniline of formula (III) to give the triphenylmethane of formula (IVA), b) treatment of the triphenylmethane of formula (IVA) with sulfuric acid to form the sulfonated triphenylmethane of formula (VA) nzaz Ln / zznz / e / γΐΛΐ 9. A process according to any one of claims 1 to 8, wherein the compound corresponding to formula (I) is selected from: (VI) (VII) patent blue, sodium salt Ca2' calcium salt. patent blue, 10. A process according to any one of claims 1 to 6, wherein the compound corresponding to formula (I) corresponds to formula (IB).

11. Process according to claim 10, wherein the compound corresponding to formula (I) is compound (VIII) isosulfan blue.

12. Crystalline form of the patent blue compound, sodium salt, corresponding to formula (VI), nzaz Ln / zznz / e / γALA characterized by the following powder X-ray diffraction pattern, measured on a diffractometer and expressed in terms of the inter-lattice distances d, the Bragg angle 2-theta, the intensity and the relative intensity (expressed as a percentage with respect to the most intense line): Angle 2-theta (°) Inter-lattice distance d (A) I (counts) I rei (%) 5.6 15.80 500 61.5 6.2 14.29 375 46.2 9.4 9.39 187.5 23.1 10 . 9 8.12 62.5 7.7 11.5 7.71 125 15.4 12.1 7.33 156.25 19.2 14.4 6.14 343.75 42.3 15.6 5.68 250 30.8 16.5 5.38 375 46.2 17.6 5.02 187.5 23.1 18.2 4.86 375 46.2 19.4 4.57 812.5 100.0 20.0 4.43 500 61.5 22.9 3.87 187.5 23.1 24.7 3.60 250 30.8 understanding that the values ​​of the The intensity (I) and relative intensity (I reí) of the previous peaks may vary by + / - 15%.

13. Pharmaceutical composition comprising at least the crystalline form of the patent blue compound, sodium salt, according to claim 12, in a pharmaceutically acceptable vehicle.