methyl 2-chloro-3-oxothiophene-2-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a similar manner as described for example C2, 8.54 g of the above-synthesized 5-methoxy-1H-imidazo[4,5-b]pyridine and 4.46 g of methyl 2-chloro-3-oxo-2,3-dihydrothiophene-2-carboxylate and 13.07 g of 2,2,6,6-tetramethylpiperidine in 620 ml chloroform yield the title compounds as an isomeric mixture which was used for the next step (example B7) without further purification.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a similar manner as described for example C2, 8.54 g of the above-synthesized 5-methoxy-1H-imidazo[4,5-b]pyridine and 4.46 g of methyl 2-chloro-3-oxo-2,3-dihydrothiophene-2-carboxylate and 13.07 g of 2,2,6,6-tetramethylpiperidine in 620 ml chloroform yield the title compounds as an isomeric mixture which was used for the next step (example B7) without further purification.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a similar manner as described for example C6, 30.0 g of 1H-imidazo[4,5-b]pyridine and 19.26 g of methyl 2-chloro-3-oxo-2,3-dihydrothiophene-2-carboxylate in 2 l chloroform give 3-hydroxy-5-imidazo[4,5-b]pyridin-3-yl-thiophene-2-carboxylic acid methyl ester (compound C8b) and the crude title compounds as an isomeric mixture which was used for the next step without further purification (example B5). The structural assignment of compound C8b was unequivocally established by two-dimensional 1H NMR experiment (NOESY, COSY).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a similar manner as described for example C6, 1.50 g of the above-synthesized 5,6-dimethoxy-1H-imidazo[4,5-b]pyridine and 0.81 g of methyl 2-chloro-3-oxo-2,3-dihydrothiophene-2-carboxylate in 40 ml chloroform yield the title compounds as an isomeric mixture which was used for the next step without further purification (example B4).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2.00 g of 6-methoxy-1H-imidazo[4,5-c]pyridine in 50 ml of chloroform were added 1.25 g of methyl 2-chloro-3-oxo-2,3-dihydrothiophene-2-carboxylate in portions and the reaction mixture was stirred for 120 h at room temperature. The reaction mixture was washed with water (3×50 ml) and the organic layer was dried and concentrated under vacuum. The residue was recrystallized from methanol to yield the title compounds as an isomeric mixture. The reaction mixture was washed with water (3×50 ml) the organic layer was dried concentrated under vacuum The residue was recrystallized from methanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a similar manner as described for example C6, 1.50 g of the above-synthesized 5,6-dimethoxy-1H-imidazo[4,5-b]pyridine and 0.81 g of methyl 2-chloro-3-oxo-2,3-dihydrothiophene-2-carboxylate in 40 ml chloroform yield the title compounds as an isomeric mixture which was used for the next step without further purification (example B4).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a similar manner as described for example C3, 1.81 g of 1H-imidazo[4,5-c]pyridine-6-carboxylic acid (2-methoxy-ethyl)-amide and 1.27 g of methyl 2-chloro-3-oxo-2,3-dihydrothiophene-2-carboxylate in 300 ml chloroform yield the title compound which was used for the next step without further purification (example B8).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a similar manner as described for example C3, 1.81 g of 1H-imidazo[4,5-c]pyridine-6-carboxylic acid (2-methoxy-ethyl)-amide and 1.27 g of methyl 2-chloro-3-oxo-2,3-dihydrothiophene-2-carboxylate in 300 ml chloroform yield the title compound which was used for the next step without further purification (example B8).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2.27 g of 1H-imidazo[4,5-c]pyridine-6-carboxylic acid (2-morpholin-4-yl-ethyl)-amide in 150 ml chloroform was slowly added a solution of 1.27 g of methyl 2-chloro-3-oxo-2,3-dihydrothiophene-2-carboxylate in 100 ml chloroform and the reaction mixture was stirred for 12 h at room temperature. The reaction mixture was washed with water (3×50 ml) and the organic layer was dried with MgSO4 and concentrated under vacuum. The residue was dissolved in dichloromethane and purified by flash chromatography (dichloromethane/methanol, elution gradient 10/0 to 9/1 (v/v))) to give the title compound. The reaction mixture was washed with water (3×50 ml) the organic layer was dried with MgSO4 concentrated under vacuum The residue was dissolved in dichloromethane purified by flash chromatography (dichloromethane/methanol, elution gradient 10/0 to 9/1 (v/v)))

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2.27 g of 1H-imidazo[4,5-c]pyridine-6-carboxylic acid (2-morpholin-4-yl-ethyl)-amide in 150 ml chloroform was slowly added a solution of 1.27 g of methyl 2-chloro-3-oxo-2,3-dihydrothiophene-2-carboxylate in 100 ml chloroform and the reaction mixture was stirred for 12 h at room temperature. The reaction mixture was washed with water (3×50 ml) and the organic layer was dried with MgSO4 and concentrated under vacuum. The residue was dissolved in dichloromethane and purified by flash chromatography (dichloromethane/methanol, elution gradient 10/0 to 9/1 (v/v))) to give the title compound. The reaction mixture was washed with water (3×50 ml) the organic layer was dried with MgSO4 concentrated under vacuum The residue was dissolved in dichloromethane purified by flash chromatography (dichloromethane/methanol, elution gradient 10/0 to 9/1 (v/v)))

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 21.2 g of 6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1H-imidazo[4,5-c]pyridine and 11.36 g of 2,2,6,6-tetramethylpiperidine in 2 l dichloromethane was slowly added a solution of 8.77 g of methyl 2-chloro-3-oxo-2,3-dihydrothiophene-2-carboxylate in 300 ml chloroform at 30-40° C. The reaction mixture was stirred for 12 h, washed with water (2×200 ml) and concentrated under vacuum. The residue was purified by flash chromatography (eluents: ethyl acetate/methanol/triethylamine) two times and after precipitation from ethyl acetate/n-hexane the title compounds were obtained as a mixture of regioisomers. washed with water (2×200 ml) concentrated under vacuum The residue was purified by flash chromatography (eluents: ethyl acetate/methanol/triethylamine) two times after precipitation from ethyl acetate/n-hexane the title compounds were obtained as a mixture of regioisomers

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 0.68 g of 6-chloro-1H-imidazo[4,5-c]pyridine and 0.65 g of 2,2,6,6-tetramethylpiperidine in 100 ml chloroform were slowly added a solution of 0.87 g of methyl 2-chloro-3-oxo-2,3-dihydrothiophene-2-carboxylate in 40 ml chloroform. The reaction mixture was stirred for 12 h at room temperature. After washing with water (3×50 ml) the organic layer was separated, dried with MgSO4 and concentrated to a volume of about 100 ml. The residue was treated with n-hexane until precipitation takes place. The solid was filtered and the procedure was repeated once again. The combined solids were dried under vacuum to yield the title compounds as an isomeric mixture, which was used for the next step (example B3) without further purification. After washing with water (3×50 ml) the organic layer was separated dried with MgSO4 concentrated to a volume of about 100 ml The residue was treated with n-hexane until precipitation The solid was filtered The combined solids were dried under vacuum