ES2275416B1 - HALOGENATED DERIVATIVES OF 4H, 5H-TIENO (3,2-B: 4,5-B ') DIPIRROLES AND PROCEDURE AND CORRESPONDING UTILIZATIONS. - Google Patents

Abstract

Halogenated derivatives of 4H, 5H-thieno [3,2-b: 4,5-b ''] diproles and corresponding procedure and uses. The present invention develops the synthesis of systems 2,7-dihalo-4H, 5H-thieno [3,2-b: 4,5-b ''] dipyroles of general formula (1), where R can be (C1-) alkyl 5), benzyl or substituted benzyl; G can be hydrogen or trimethylsilylethoxymethyl (SEM) and X can be chlorine, bromine or iodine. The use of the compounds (1) is described as a background of 2,2 '' -4,4''-substituted diaryls and substituted precursors of positions 2,7,12,17 by alkenyl, aryl or heteroaryl groups .

Description

Halogenated derivatives of 4 H , 5 H -thieno [3,2- b : 4,5- b ' ] dipyroles and corresponding procedure and uses.

Field of the Invention

The present invention relates to the halogenated derivatives of 4 H , 5 H -thieno [3,2- b : 4,5- b ' ] dipyroles of general formula 1, and a process for obtaining them.

one

where R can be alkyl C 1-5, benzyl or substituted benzyl, G can be  hydrogen or trimethylsilylethoxymethyl (SEM) and X can be chlorine, bromine or iodine

State of the art

Currently, in the fight against cancer, It has, mainly, three types of treatments: surgery, Radiation therapy and chemotherapy. Despite his partial successes they present great inconveniences like the trauma post-operative, immunosuppression or toxicity produced by the low selectivity of the drugs. With the purpose of improve and / or complement these conventional therapies, in the In recent years, new forms of treatment have emerged such as Photodynamic Therapy (PDT).

PDT consists of administering a photosensitizing drug topically or systemically, which once accumulated in the neoplastic tissue, because the tumors have greater vascularization, but poor lymphatic drainage, is irradiated with a laser beam. The action of light on the photosensitizer produces the photodynamic effect, that is, the generation of toxic oxidizing species, mainly singlet oxygen, producing apoptosis or cell necrosis. Thus, it is a doubly selective technique. The photodynamic effect has also been applied in dermatology, and in the inactivation of viruses such as HIV and bacteria (G. Jori, D. Tonlorenzi, Int. Photodyn . 1999 , 2 (1), 2-3).

Currently, the therapy is applied using of a naturally occurring photosensitizer called Photofrin® II. However, it has several drawbacks. First, the drug is, chemically, a complex mixture of oligomers of hematoporphyrin which causes low reproducibility in the treatments Second, its maximum absorption is very high. below the wavelength range in which the skin is transparent. It also has a great phototoxicity due to the slowness with which it is eliminated from the organism. These facts limit The technique.

So, an ideal photosensitizer should have the following characteristics:

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Chemical stability and photochemistry.

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Structure perfectly determined.

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Absorption coefficient the most high possible between 650 and 800 nm.

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High quantum yield of triplet or formation of active oxygen species.

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Location in tumors

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Minimum toxicity in the absence of light.

?

Ease of disposal of organism.

In order to improve the properties of the Photofrin® II have appeared second photosensitizers generation. These include porphyrins, chlorines, bacteriochlorines, azaporphyrins, glitter, M (II) -texaphyrins, phthalocyanines, naphthalocyanines and the porficenos (2).

2

Indeed, the porficen (2, R1 = H), discovered by E. Vogel in 1986 (E.Vogel, M. Köcher, H. Schmickler, J. Lex, Angew. Chem. Int. Ed. Engl 1986 , 25 , 257-259), can be considered a structural isomer of porphyrin which has a maximum absorption at 630 nm (G. Jori, E. Vogel, AD Cross, Cytopharm, Inc., US 4,913907) .

The 2,7,12,17-tetraphenylporphene (2, R1 = Ph) described by a group comprising some of the inventors of the present invention (S. Nonell, N. Bou, JI Borrell, J. Teixidó , A. Villanueva, A. Juarranz, M. Cañete, Tetrahedron Lett . 1995 , 36 , 3405-3408), presents a 30 nm batochromic displacement relative to the unsubstituted porcelain. The photophysical properties of the derivative G = Ph, and its complex with palladium have been studied and make it a strong candidate for photodynamic cancer therapy (M. Cañete, M. Lapeña, A. Juarranz, V. Vendrell, JI Borrell, J. Teixidó, S. Nonell, A. Villanueva, Anti-Cancer Drug Design , 1997 , 12 , 543-554; M. Cañete, A. Ortiz, A. Juarranz, A. Villanueva, S. Nonell, JI Borrell, J Teixidó, JC Stockert, Anti-cancer Drug Design , 2000 , 15 , 143-150).

However, the porficenos are synthesized through an eight-step linear synthesis that incorporates the R 1 substituents from the beginning. This fact makes it difficult, or it can even make it impossible to generate derivatives able to model the properties of the photosensitizer.

Thus, the design of photosensitizers that on the one hand have a maximum of absorption shifted towards red and that on the other hand, it get for a synthetic itinerary that allows a focus combinatorial in order to incorporate substituents to improve properties such as selectivity or solubility.

The real possibility of incorporating substituents very diverse in porficénicos skeletons expands the possibilities noted in the literature of using the porficenos for others applications, both biomedical and industrial. You could quote as examples the storage units (TW552262, JP2002137547, JP2002114923), photosensitizers for Photography (US6372419, JP2001100353) or even oxygen sensors (JP2003344382).

From the synthetic point of view it turns out attractive a strategy that allows introducing substituents in positions 4 and 4 'of a preformed bipyrrolic system. For it is necessary to have a bipyrrole with halogens in these positions. There are currently many synthetic possibilities to functionalize halogenated heterocycles, between the reactions Organometallic ones stand out those catalyzed by Pd. The reaction of Suzuki for example would allow to introduce aromatic substituents in the heterocycle. The possibilities are very diverse since there is a wide variety of commercial boronic acids for Perform Suzuki's reaction.

In our group, Suzuki's reaction to 2,2'-biimidazole systems has already been carried out as a strategy to obtain azaporficenos (S. Nonell, JI Borrell, S. Borrós, C. Colominas, O. Rey, N. Rubio, D. Sánchez, J. Teixidó, Eur. J. Org. Chem ., 2003 , 1635-1640); The present invention uses halogenated thienodiproles 1 as a background of substituted 2,2'-biproles 4,4'-diaryl capable of being transformed into porficenos 2 by chemical reactions previously described by our team (A. Gavaldá, JI Borrell, J. Teixidó , S. Nonell, O. Arad, R. Grau, M. Cañete, A. Juarranz, A. Villanueva, JC Stockert, J. Porphyrins Phthalocyanines , 2001 , 5 , 846-852).

Object of the invention

The authors of the present invention have designed a new procedure or itinerary that allows the obtaining of the new halogenated thipedipers 1 from 4 H , 5 H -thieno [3,2- b : 4,5- b ] dipyrrol-3, Di (R) 6-dicarboxylates (3), where R can be C 1-5 alkyl, benzyl or substituted benzyl.

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3

The object of the invention is also the preferred use of said compounds 1 as a background of 2,2'-dipyroles 4,4'-diaryl substituted as precursors of porficenos 2 substituted in the positions 2,7,12,17 by alkenyl, arite or heteroaryl groups.

Detailed description of an embodiment of the invention

The procedure for obtaining thienodiproles 1 begins with the obtaining of 4 H , 5 H -thieno [3,2- b : 4,5- b ' ] dipyrrol-3,6-dicarboxylates of di (R) (3 ) by the procedure described in 1976 by Farnier et al . for the synthesis of 4 H , 5 H -thieno [3,2- b : 4,5- b ' ] diethyl dipyrrol-3,6-dicarboxylate (3, R = Et) (M. Farnier, S. Soth, P. Fournari, Can. J. Chem . 1976 , 54 , 1074-1082). Thus, the commercially available thiophene-2,5-dicarboxaldehyde (4) is treated with the corresponding azidoacetate of (R) (5), where R is C 1-5 alkyl, benzyl or substituted benzyl, in the presence of ROH alcohol and molecular sodium to yield 2,5-bis (2-azido-2- (R) oxycarbonylvinyl) thiophene (6), where R is C 1-5 alkyl, benzyl or substituted benzyl. Compounds 6 are transformed into the corresponding 4 H , 5 H -thieno [3,2- b : 4,5- b ' ] di (R) dipyrrol-3,6-dicarboxylate (3) by heating in xylene. The diester 3 is the common intermediate from which halogenated thienodiproles 1 are obtained. The R group is preferably the ethyl group.

4

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The process for obtaining compounds 1 (R = Et) begins with the halogenation of thienodipyrrole 3 (R = Et). The difficulties encountered in brominating 3 (R = Et) with various traditional brominating agents in the chemistry of pyrroles such as N- bromosuccinimide, 1,3-dibromo-5,5-dimethylhydantoin, etc. in a large number of solvents, led to the inventors of the present invention to test elemental bromine as a brominating agent even though it is not commonly used in pyrroles.

Surprisingly when dealing with bromine the thienodipyrrole 3 (R = Et) using a 5: 2 mixture of acetate ethyl and acetic acid as solvent is obtained by precipitation dibromothienodipyrrole 1 (R = Et, X = Br, G = H) with a yield of 90%. Such precipitation does not occur with the diiodinated derivative, in principle more reactive than brominated for a subsequent reaction of  Suzuki, which makes the use of column chromatography necessary For your isolation. On the other hand, the dichlorinated derivative, obtainable by treatment with Cl 2, it is of less interest because it is less reagent than dibromado in Suzuki conditions. All this does that the dibromated derivative 1 (R = Et, X = Br, G = H) be the compound suitable for subsequent synthetic manipulations.

5

Numerous tests have been done with dibrominated thienodipyrrole 1 (R = Et, X = Br, G = H) and it has been concluded that this molecule does not give Suzuki reaction with good yields. Examples of Suzuki in pyroles appear in the literature where this problem is solved by protecting the nitrogens of the heterocycle (Handy et.al., Tetrahedron. Lett . 2003 , 44 , 427-430, Ghosez et.al. , Can. J. Chem . 2001 , 79 , 1827-1839). Taking into account these precedents, the protection of the brominated thienodipyrrole 1 nitrogens was tested (R = Et, X = Br, G = H).

Protection with methyl chloroformate in presence of tetrabutylammonium iodide and sodium carbonate leads to the methylation of nitrogen. Since the methyl group is a protective group very difficult to eliminate, this is not a good approach. Protection with methyl chloroformate was attempted by prior ionization with sodium hydride but only managed to protect one of the nitrogen, which is insufficient to be able to carry out the Suzuki reaction.

Finally, simultaneous protection of the two nitrogens of 1 (R = Et, X = Br, G = H) has been achieved by the trimethylsilylethoxymethyl protecting group (abbreviated as SEM) by treatment with trimethylsilylethyloxymethyl chloride (SEM-Cl) in THF using NaH as a base to yield 2,7-dibromo-4 H , 5 H- bis (trimethylsilylethoxymethyl) thieno [3,2- b : 4,5- b ' ] diethyl dipyrrol-3,6-dicarboxylate 1 (R = Et, X = Br, G = SEM).

The SEM, although bulky, allows double protection, unlike other bulky protective groups but of nonlinear structure. This double protection must be perform at room temperature because if done at low temperature only the term of protection 7 is obtained. In addition, the SEM is very stable in a wide variety of conditions. which allows the subsequent use of said molecule in Halogen substitution reactions with other residues. Other advantage of this protective group is to give solubility thienodipyrrole in numerous organic solvents, including the hexane, which allows its application in numerous reactions that they give in the middle apolar.

6

It has been found that it is possible to replace the two halogens of halogenated thienodiproles 1, whose annular nitrogens are protected with the SEM group, by alkenyl, aryl or heteroaryl moieties by Suzuki reaction under conditions similar to those previously described by our group to obtain azaporficenos (S. Nonell, JI Borrell, S. Borrós, C. Colominas, O. Rey, N. Rubio, D. Sánchez, J. Teixidó, Eur. J. Org. Chem ., 2003 , 1635-1640), So , 2,7-dibromo-4 H , 5 H -bis (trimethylsilylethoxymethyl) thieno [3,2- b : 4,5- b ' ] diethyl dipyrrol-3,6-dicarboxylate 1 (R = Et, X = Br, G = SEM) undergoes Suzuki reaction in dioxane and in the presence of a palladium catalyst, such as the tetrakis (triphenylphosphine) palladium (0) complex, and of a base, such as sodium carbonate or cesium fluoride, with a boronic derivative 8, where R2 can be hydrogen (boronic acid) or both R2 form part of the same hydrocarbon chain (boronic ester of propylene glycol that of pinacol) and R 1 may be an alkenyl group (vinyl or styryl), or an aryl group which may be unsubstituted or substituted by one or more C 1-6 alkyl, C 1- alkoxy groups 6}, hydroxy, amino, mono- or dialkylamino or hydroxycarbonyl, or a heteroaryl group which may be unsubstituted or substituted by one or more C 1-6 alkyl groups to yield the corresponding disubstituted system 9.

7

The systems 9 can be transformed into substituted 5,5'-diformyl-2,2'-biproles.4,4'-di (R1) (where R1 can be alkenyl, aryl or heteroaryl according to the previous definition), immediate precursors of 2,7,12,17-tetrasubstituted porphors 2, by desulfurization according to the method described by Farnier et al . (M. Farnier, S. Soth, P. Fournari, Can. J. Chem . 1976 , 54 , 1074-1082), followed by removal of the SEM protecting group according to the method described by Delgado (A. Delgado, J. Clardy, J. Org. Chem . 1993 , 58 , 2862-2866) and subsequent transformation of the ester groups into aldehyde according to the method previously described by our group (A. Gavaldá, JI Borrell, J. Teixidó, S. Nonell, O. Arad , R. Grau, M. Cañete, A. Juarranz, A. Villanueva, JC Stockert, J. Porphyrins Phthalocyanines , 2001 , 5 , 846-852).

8

In addition, the 2,2'-bipirroles 10 they are intermediate in the synthesis of numerous photosensitizers to part of the porficenos (corroles, safirinas, rosarinas, rubirinas, ...). Therefore the application of the Tienodiproles 1 to the synthesis of other photosensitizers.

Next, for a better understanding of the present invention, without it being construed as limitations to it, the following are exposed

Examples Example 1 Obtaining 2,7-dibromo-4 H , 5 H -thieno [3,2- b : 4,5- b ' ] diethyl dipyrrol-3,6-dicarboxylate 1 (R = Et, X = Br, G = H)

A solution of 3 mL of Br 2 in 45 mL of AcOH is added on a suspension of 3.0 g (9.7 mmol) of thienodipyrrole 3 (R = Et) in a mixture of 250 mL of AcOEt and 100 mL of AcOH. It is then stirred for eight hours at room temperature. The resulting precipitate is filtered, washed with 3x50 mL of aqueous NaHCO3 solution and, finally, dried in a vacuum desiccator at 50 ° C over phosphorus pentoxide. 4.1 g (8.7 mmol, 89%) of 1 (R = Et, X = Br, G = H) are obtained as a white solid, e.g. fus. > 290 (d). IR (KBr) ν (cm -1): 3417, 3327, 2924, 2853, 1686, 1649, 1375, 1230; 1 H-NMR (DMSO-d 6, 300 MHz) δ (ppm): 11.52 (s, 2H, NH), 4.34 (q, 4H, J = 7.2Hz, OC H 2 CH 3), 1.35 (t, 6H, J = 7.2Hz, O-CH 2 C H 3); 13 C-NMR (DMSO-d 6, 75.5 MHz) δ (ppm): 158.9, 127.7, 125.2, 121.9, 96.1, 60.6, 14.3; MS (70 eV): m / z = 463.6 ([M + 2H] +), 419.6, 371.6, 264.7; HRMS (High Resolution Mass Spectrometry - High Resolution Mass Spectrometry): C_ {14} H_ {12} Br_ {N} {2} O4 {S}, calculated: 461.8884, obtained: 461.8892; Elemental Analysis (EA) Calculated for C 14 H 12 Br 2 N 2 O 4 S: C, 36.23; H, 2.61; N, 6.04; S, 6.91. Obtained: C, 36.11; H, 2.54; N, 5.98; S, 6.59.

Example 2 Obtaining 2,7-dibromo-4 H , 5 H -bis (trimethylsilylethoxymethyl) thieno [3,2- b : 4,5- b ' ] diethyl dipyrrol-3,6-dicarboxylate 1 (R = Et, X = Br, G = SEM)

A suspension of 11 g (24 mmol) of dibromothienobipyrrole 1 (R = Et, X = Br, G = H) is made in 50 mL of anhydrous THF under an argon atmosphere. Then, in small portions, 2.1 g (0.52 mol) of 60% NaH in paraffin is added. The resulting mixture is allowed to stir for 15 min at room temperature. 15 mL (80 mmol) of trimethylsilylethoxymethyl chloride (SEM-Cl) are added slowly and allowed to stir for 1 hour at room temperature. 100 g of ice are added and stirred until a precipitate appears. The resulting precipitate is filtered, washed with MeOH until the solid is white and dried in a vacuum desiccator at 50 ° C on phosphorus pentoxide to obtain 13.4 g (18 mmol, 77%) of 1 (R = Et, X = Br , G = SEM). The mother liquors are extracted with hexane, dried over MgSO4, and the solvent is removed in vacuo recovering 3.0 g (4 mmol, 17%) more than 1 (R = Et, X = Br, G = SEM), p. fus. 127-129 ° C. IR (KBr) ν (cm -1): 2952, 2902, 1705, 1382, 1319, 1228, 1088, 920, 859, 835; 1 H-NMR (CDCl 3, 300 MHz) δ (ppm): 6.27 (s, 4H, N-CH 2), 4.41 (q, 4H, J = 7.2Hz, OC H _ {2} {3} CH), 3.51 (t, 4H, J = 8.4Hz, O-CH {2}), 1.45 (t, 6H, J = 7.2Hz, O-CH {2} {3 C H }); 0.83 (t, 4H, J = 8.4 Hz, Si-CH 2), -0.07 (s, 18H, Si- (CH 3) 3); 13 C-NMR (CDCl 3, 75.5 MHz) δ (ppm): 160.5, 130.7, 128.5, 123.9, 99.6, 75.0, 65.9, 61.1, 17.9, 14.4, -1.4; MS (ESI-TOF): m / z = 747.0 ([M + Na + 2H] +), 337.3, 236.1, 218.2, 163.0. HRMS (MALDI-TOF): C 26 H 40 Br 2 N 2 O 6 SSi 2 + Na, Calculated: 745.041; obtained 745,040; AE: Calculated for C 26 H 40 Br 2 N 2 O 6 SSi 2: C, 43.09; H, 5.56; N, 3.87; S, 4.42. Obtained: C, 43.25; H, 5.37; N, 3.64; S, 4.21.

Example 3 Obtaining 2,7-diphenyl-4 H , 5 H -bis (trimethylsilylethoxymethyl) thieno [3,2- b , 4,5- b ' ] diethyl dipyrrol-3,6-dicarboxylate 9 (R1 = Ph)

100 mg (138 µmol) of 2,7-dibromo-4 H , 5 H -di (trimethylsilylethoxymethyl) thieno [3,2- b : 4,5- b ' ] diethyl dipyrrol-3,6-dicarboxylate are dissolved 1 (R = Et, X = Br, G = SEM), 50 mg (410 µm) of phenylboronic acid 8 (R 1 = Ph, R 2 = H) in 60 mL of 1.4- dioxane Next, a saturated aqueous solution of 57 mg (412 µm) of potassium carbonate in 1 mL of water is added and the entire mixture is deoxygenated with N2 for half an hour. Finally, 25 mg (22 µm) of palladium tetrakis (triphenylphosphine) (0) are added and the mixture is refluxed under an argon atmosphere for 16 hours. The resulting solution is allowed to cool, 30 mL of water are added and extracted with 3x50 mL of hexane.

The organic extracts are dried over MgSO4, the solvent is removed in vacuo and the residue is chromatographed using a 1: 2 mixture of ethyl acetate / hexane as eluent. 76 mg (106 µmol, 77%) of 9 (R1 = Ph) are obtained as a white solid, e.g. fus. 90-92 ° C. IR (KBr) ν (cm -1): 3061, 3029, 2980, 2953, 2897, 1948, 1882, 1698 1397, 1382, 1317, 1249, 1238, 1179, 1101, 1078, 860, 836, 699; 1 H-NMR (CDCl 3, 300 MHz) δ (ppm): 7.5-7.3 (m, 10H, Ph), 6.33 (s, 4H, N-CH 2), 4.14 (q, 4H, J = 6.9Hz, OC H 2 CH 3), 3.61 (t, 4, J = 8.4Hz, O-CH 2), 1.05 (t, 2H, J = 6.9 Hz, O-CH 2 C H 3), 0.91 (t, 4H, J = 8.4 Hz, Si-CH 2), -0.04 (s, 18H, Si- (CH 3) _{3}); 13 C-NMR (CDCl 3, 75.5 MHz) δ (ppm): 161.8, 134.5, 129.9, 129.2, 128.7, 127.8, 127.2, 126.8, 122.5, 74.6, 65.7, 60.5, 18.0, 13.8, -1.3. MS (ESI-TOF): m / z = 741.5 ([M + Na] +), 601.4, 416.5, 368.5, 288.4.

Claims (8)

1. Compound of formula 1, where R can be C 1-5 alkyl, benzyl or substituted benzyl, G it can be hydrogen or trimethylsilylethoxymethyl (SEM) and X can be chlorine, bromine or iodine: 9 2. Compound according to claim 1, characterized in that G = SEM, R = Et and X = Br. 10 3. Compound according to claim 1, characterized in that G = H, R = Et and X = Br. eleven 4. A process for the preparation of a compound of formula 1 according to at least one of claims 1 to 3 characterized in that it comprises the following steps:

(to)

Halogenar 4 H , 5 H -thieno [3,2- b : 4,5- b ' ] di (R) dipyrrol-3,6-dicarboxylate (3), to yield 2,7-dihalo-4 H , 5 H -thieno [3,2- b : 4,5- b ' ] di (R) dipyrrol-3,6-dicarboxylate (1) (G = H).

12

(b)

Optionally, protect the nitrogens of thienodipyrrole 2,7-dihalo substituted 1 (G = H) with trimethylsilylethoxymethyl chloride to obtain 2,7-dihalo-4 H , 5 H -bis (trimethylsilylethoxymethyl) thieno [3,2- b : 4,5- b '] dipyrrole-3,6-dicarboxylate di (R) (1) (G = SEM).

13 5. A procedure for the preparation of a compound of formula 1 (R = Et, X = Br, G = SEM) as has been defined in the second claim comprising: 14

(to)

Bromine 4 H , 5 H -thieno [3,2- b : 4,5- b ' ] diethyl dipyrrol-3,6-dicarboxylate 3 (R = Et) to yield 2,7-dibromo-4 H , 5 H -thieno [3,2- b : 4,5- b ' ] diethyl dipyrrol-3,6-dicarboxylate 1 (R = Et, X = Br, G = H).

fifteen

(b)

Protect the nitrogens of substituted 2,7-dibromo thienodipyrrole 1 (R = Et, X = Br, G = H) with trimethylsilylethoxymethyl chloride to obtain 2,7-dibromo-4 H , 5 H -bis (trimethylsilylethoxymethyl) thieno [ 3,2- b : 4,5- b ' ] diethyl dipyrrol-3,6-dicarboxylate 1 (R = Et, X = Br, G = SEM).

6. A process for the preparation of a compound of formula 1 (R = Et, X = Br, G = SEM) as defined in the third claim which consists of protecting the nitrogens of 2,7-dibromo-4 H , 5 H -thieno [3,2- b : 4,5- b ' ] diethyl dipyrrol-3,6-dicarboxylate 1 (R = Et, X = Br, G = H) with trimethylsilylethoxymethyl chloride (SEM-Cl) to obtain 2,7-dibromo-4 H , 5 H -bis (trimethylsilylethoxymethyl) thieno [3,2- b : 4,5- b ' ] diethyl dipyrrol-3,6-dicarboxylate 1 (R = Et, X = Br, G = SEM). 16 7. A process for the preparation of a compound of formula 1 (R = Et, X = Br, G = H) as defined in the second claim comprising: brominating 4 H , 5 H -thieno [3,2 - b : 4,5- b ' ] diethyl dipyrrol-3,6-dicarboxylate 3 (R = Et) to yield 2,7-dibromo-4 H , 5 H -thieno [3,2- b : 4, 5- b ' ] diethyl dipyrrol-3,6-dicarboxylate 1 (R = Et, X = Br, G = H). 17 8. A process for the transformation of a compound of formula 1 (R = Et, X = Br, G = SEM) into a compound 9, where R 1 can be an alkenyl group (vinyl or styryl), or a arito group which may be unsubstituted or substituted by one or more C 1-6 alkyl, C 1-6 alkoxy, hydroxy, amino, mono- or dialkylamino or hydroxycarbonyl groups, or a heteroaryl group which may be not substituted or substituted by one or more C 1-6 alkyl groups, comprising: subjecting 1 (R = Et, X = Br, G = SEM) to the reaction of Suzuki in dioxane and in the presence of a palladium catalyst , such as the tetrakis (triphenylphosphine) palladium (0) complex, and a base, such as sodium carbonate or cesium fluoride, with a boronic derivative 8, where R2 can be hydrogen (boronic acid) or both R2 2} be part of the same hydrocarbon chain (boronic ester of propylene glycol or pinacol) to yield 2,7-di (R 1) -4 H , 5 H -bis (trimethylsilylethoxymethyl) thieno [3,2- b : 4,5- b ' ] diethyl dipyrrol-3,6-dicarboxylate 9. 18