penta-1,4-dien-3-ol

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,4-Pentadien-3-ol (200 mg, 2.38 mmol) and IBX (999 mg, 3.57 mmol) were dissolved in DCE (15 mL) and heated at 70° C. for 3 h. The reaction mixture was filtered, diluted with MeOH (10 mL) and 2-fluoro-1-fluoromethyl-ethylamine (226 mg, 2.38 mmol) was added. The reaction mixture was stirred at 70° C. for 3 h. Isocyanate resin was added and the reaction mixture stirred at room temperature for 6 h, filtered and concentrated in vacuo to give the crude title compound (160 mg, 38%) as an orange gum. LCMS (ES+): 178.1 [MH]+. The reaction mixture was filtered was added the reaction mixture stirred at room temperature for 6 h filtered concentrated in vacuo

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,4-Pentadien-3-ol (200 mg, 2.38 mmol) and IBX (999 mg, 3.57 mmol) were dissolved in DCE (15 mL) and heated at 70° C. for 3 h. The reaction mixture was filtered, diluted with MeOH (10 mL) and 2-fluoro-1-fluoromethyl-ethylamine (226 mg, 2.38 mmol) was added. The reaction mixture was stirred at 70° C. for 3 h. Isocyanate resin was added and the reaction mixture stirred at room temperature for 6 h, filtered and concentrated in vacuo to give the crude title compound (160 mg, 38%) as an orange gum. LCMS (ES+): 178.1 [MH]+. The reaction mixture was filtered was added the reaction mixture stirred at room temperature for 6 h filtered concentrated in vacuo

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-(4-{5′-[4-(4-Carboxy-butyl)-phenyl]-[2,2′]bithiophenyl-5-yl}-phenyl)-pentanoic acid (1.05 g, 2.02 mmol) and 1,4-pentadien-3-ol (0.42 g, 5.0 mmol) are suspended in NMP (52 mL). 1-(3-Dimethlaminopropyl)-3-ethylcarbodiimide hydrochloride [EDCI] (0.96 g, 5.0 mmol) is added, followed by 4-dimethylaminopyridine (0.61 g, 4.9 mmol) and the mixture is warmed to 50° C. for 10 min. The resulting solution is stirred at room temperature for 3 days. The mixture is poured into water (300 ml) and the resulting precipitate filtered. The solid is dissolved in THF (300 mL), filtered and dry loaded onto silica. The silica is loaded onto a dry silica column and eluted with petrol/dichloromethane (4:1) to remove non-coloured products. The eluent is changed to chloroform and the coloured fractions are collected to afford crude product (1.06 g). A portion (0.5 g) is further purified by reverse phase chromatography (eluent: acetonitrile/THF 9:1 to 1:1, gradient). Final recrystallisation from ethyl acetate afforded the product (0.15 g). 1H NMR (300 MHz, CDCl3): δ (ppm) 7.51 (d, 4H), 7.20 (s, 4H), 7.14 (d, 4H), 5.83 (m, 4H), 5.71 (m, 2H), 5.25 (m, 8H), 2.64 (t, 4H), 2.38 (t,0 4H), 1.73-1.63 (m, 8H); 13C NMR (75 MHz, CDCl3): δ (ppm) 172.4, 143.2, 142.8, 136.4, 135.2, 129.0, 125.6, 125.5, 124.4, 123.4, 117.4, 74.9, 34.9, 34.0, 30.1, 25.9. m.p. (° C.) K 75 SX 174 I. the resulting precipitate filtered The solid is dissolved in THF (300 mL) filtered dry eluted with petrol/dichloromethane (4:1) to remove non-coloured products the coloured fractions are collected to afford crude product (1.06 g) A portion (0.5 g) is further purified by reverse phase chromatography (eluent: acetonitrile/THF 9:1 to 1:1, gradient) Final recrystallisation from ethyl acetate

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-(4-{5′-[4-(4-Carboxy-butyl)-phenyl]-[2,2′]bithiophenyl-5-yl}-phenyl)-pentanoic acid (1.05 g, 2.02 mmol) and 1,4-pentadien-3-ol (0.42 g, 5.0 mmol) are suspended in NMP (52 mL). 1-(3-Dimethlaminopropyl)-3-ethylcarbodiimide hydrochloride [EDCI] (0.96 g, 5.0 mmol) is added, followed by 4-dimethylaminopyridine (0.61 g, 4.9 mmol) and the mixture is warmed to 50° C. for 10 min. The resulting solution is stirred at room temperature for 3 days. The mixture is poured into water (300 ml) and the resulting precipitate filtered. The solid is dissolved in THF (300 mL), filtered and dry loaded onto silica. The silica is loaded onto a dry silica column and eluted with petrol/dichloromethane (4:1) to remove non-coloured products. The eluent is changed to chloroform and the coloured fractions are collected to afford crude product (1.06 g). A portion (0.5 g) is further purified by reverse phase chromatography (eluent: acetonitrile/THF 9:1 to 1:1, gradient). Final recrystallisation from ethyl acetate afforded the product (0.15 g). 1H NMR (300 MHz, CDCl3): δ (ppm) 7.51 (d, 4H), 7.20 (s, 4H), 7.14 (d, 4H), 5.83 (m, 4H), 5.71 (m, 2H), 5.25 (m, 8H), 2.64 (t, 4H), 2.38 (t,0 4H), 1.73-1.63 (m, 8H); 13C NMR (75 MHz, CDCl3): δ (ppm) 172.4, 143.2, 142.8, 136.4, 135.2, 129.0, 125.6, 125.5, 124.4, 123.4, 117.4, 74.9, 34.9, 34.0, 30.1, 25.9. m.p. (° C.) K 75 SX 174 I. the resulting precipitate filtered The solid is dissolved in THF (300 mL) filtered dry eluted with petrol/dichloromethane (4:1) to remove non-coloured products the coloured fractions are collected to afford crude product (1.06 g) A portion (0.5 g) is further purified by reverse phase chromatography (eluent: acetonitrile/THF 9:1 to 1:1, gradient) Final recrystallisation from ethyl acetate

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-(4-{5′-[4-(4-Carboxy-butyl)-phenyl]-[2,2′]bithiophenyl-5-yl}-phenyl)-pentanoic acid (1.05 g, 2.02 mmol) and 1,4-pentadien-3-ol (0.42 g, 5.0 mmol) are suspended in NMP (52 mL). 1-(3-Dimethlaminopropyl)-3-ethylcarbodiimide hydrochloride [EDCI] (0.96 g, 5.0 mmol) is added, followed by 4-dimethylaminopyridine (0.61 g, 4.9 mmol) and the mixture is warmed to 50° C. for 10 min. The resulting solution is stirred at room temperature for 3 days. The mixture is poured into water (300 ml) and the resulting precipitate filtered. The solid is dissolved in THF (300 mL), filtered and dry loaded onto silica. The silica is loaded onto a dry silica column and eluted with petrol/dichloromethane (4:1) to remove non-coloured products. The eluent is changed to chloroform and the coloured fractions are collected to afford crude product (1.06 g). A portion (0.5 g) is further purified by reverse phase chromatography (eluent: acetonitrile/THF 9:1 to 1:1, gradient). Final recrystallisation from ethyl acetate afforded the product (0.15 g). 1H NMR (300 MHz, CDCl3): δ (ppm) 7.51 (d, 4H), 7.20 (s, 4H), 7.14 (d, 4H), 5.83 (m, 4H), 5.71 (m, 2H), 5.25 (m, 8H), 2.64 (t, 4H), 2.38 (t,0 4H), 1.73-1.63 (m, 8H); 13C NMR (75 MHz, CDCl3): δ (ppm) 172.4, 143.2, 142.8, 136.4, 135.2, 129.0, 125.6, 125.5, 124.4, 123.4, 117.4, 74.9, 34.9, 34.0, 30.1, 25.9. m.p. (° C.) K 75 SX 174 I. the resulting precipitate filtered The solid is dissolved in THF (300 mL) filtered dry eluted with petrol/dichloromethane (4:1) to remove non-coloured products the coloured fractions are collected to afford crude product (1.06 g) A portion (0.5 g) is further purified by reverse phase chromatography (eluent: acetonitrile/THF 9:1 to 1:1, gradient) Final recrystallisation from ethyl acetate

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

Procedure: A mixture of 6-[5-iodo-(2-thienyl)]methoxyhexanoic acid (13.20 g, 37.3 mmol), 1,4-pentadien-3-ol (3.13 g, 37.3 mmol), dicyclohexylcarbodiimide (7.70 g, 37.3 mmol) and 4-dimethylaminopyridine (0.1 g) in DCM (250 mL) is stirred for 12 h under nitrogen. The solid is removed by filtration and the filtrate is evaporated under reduced pressure. The residue is purified by column chromatography on silica, eluting with petroleum ether/diethyl ether (90:10), to give the product as a brown oil (12.27 g, 77%) NMR showed the expected signals. The solid is removed by filtration the filtrate is evaporated under reduced pressure The residue is purified by column chromatography on silica eluting with petroleum ether/diethyl ether (90:10)

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

Procedure: A mixture of 6-[5-iodo-(2-thienyl)]methoxyhexanoic acid (13.20 g, 37.3 mmol), 1,4-pentadien-3-ol (3.13 g, 37.3 mmol), dicyclohexylcarbodiimide (7.70 g, 37.3 mmol) and 4-dimethylaminopyridine (0.1 g) in DCM (250 mL) is stirred for 12 h under nitrogen. The solid is removed by filtration and the filtrate is evaporated under reduced pressure. The residue is purified by column chromatography on silica, eluting with petroleum ether/diethyl ether (90:10), to give the product as a brown oil (12.27 g, 77%) NMR showed the expected signals. The solid is removed by filtration the filtrate is evaporated under reduced pressure The residue is purified by column chromatography on silica eluting with petroleum ether/diethyl ether (90:10)

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

Procedure: A mixture of 6-[5-iodo-(2-thienyl)]methoxyhexanoic acid (13.20 g, 37.3 mmol), 1,4-pentadien-3-ol (3.13 g, 37.3 mmol), dicyclohexylcarbodiimide (7.70 g, 37.3 mmol) and 4-dimethylaminopyridine (0.1 g) in DCM (250 mL) is stirred for 12 h under nitrogen. The solid is removed by filtration and the filtrate is evaporated under reduced pressure. The residue is purified by column chromatography on silica, eluting with petroleum ether/diethyl ether (90:10), to give the product as a brown oil (12.27 g, 77%) NMR showed the expected signals. The solid is removed by filtration the filtrate is evaporated under reduced pressure The residue is purified by column chromatography on silica eluting with petroleum ether/diethyl ether (90:10)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,4-Pentadien-3-ol (200 mg, 2.38 mmol) and IBX (999 mg, 3.57 mmol) were dissolved in DCE (15 mL) and heated at 70° C. for 3 h. The reaction mixture was filtered, diluted with MeOH (10 mL) and 2-fluoro-1-fluoromethyl-ethylamine (226 mg, 2.38 mmol) was added. The reaction mixture was stirred at 70° C. for 3 h. Isocyanate resin was added and the reaction mixture stirred at room temperature for 6 h, filtered and concentrated in vacuo to give the crude title compound (160 mg, 38%) as an orange gum. LCMS (ES+): 178.1 [MH]+. The reaction mixture was filtered was added the reaction mixture stirred at room temperature for 6 h filtered concentrated in vacuo