(E)-3-phenylprop-2-enoyl chloride

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

Procedure: The titled compound was prepared from 2-amino-5-methyl-N-(2-pyridyl)aniline and (E)-cinnamoyl chloride according to the preparation of (E)-1-(2-pyridyl)-2-styryl-1H-benzimidazole (Example 1, method A).

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

Procedure: The titled compound was prepared from 2-(2-amino-4-nitroanilino)pyridine (Runti, C. Ann. Chim. (Rome), 1956, 46, 406) and (E)-cinnamoyl chloride according to the preparation of (E)-1-(2-pyridyl)-2-styryl-1H-benzimidazole (Example 1, method A).

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

Procedure: (E)-5-Cyano-1-(2-pyridyl)-2-styryl-1H-benzimidazole was prepared from 2-amino-4-cyano-N-(2-pyridyl)aniline and (E)-cinnamoyl chloride according to the preparation of (E)-1-(2-pyridyl)-2-styryl-1H-benzimidazole (Example 1, method A).

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

Procedure: The titled compound was prepared from 2-amino-N-(2-pyridyl)-4-trifluoromethylaniline and (E)-cinnamoyl chloride according to the preparation of (E)-1-(2-pyridyl)-2-styryl-1H-benzimidazole (Example 1, method A).

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

Procedure: To a stirred suspension of N-(3-pyridyl)-o-phenylenediamine (0.93 g, 5 mmol; Kirsch, P.; Schoenleben-Janas, A.; Schirmer, R. H. Liebigs Ann. Org. Bioorg. Chem., 1995, 7, 1275) in xylene (60 ml) was added (E)-cinnamoyl chloride (0.83 g, 5 mmol). After stirring at the room temperature for 1 h, the resulting mixture was heated to reflux removing water using a Dean-Stark apparatus for 11 h. After cooling, the reaction mixture was concentrated to dryness. The residue was dissolved into ethyl acetate (100 ml), washed consecutively with saturated aqueous sodium bicarbonate solution (50 ml) and brine (50 ml), dried (magnesium sulfate) and concentrated to dryness. The residue was purified by column chromatography (silica gel, 165 g; n-hexane/ethyl acetate (3/2 to 1/1)) to give 0.77 g (34%) of brown solids. Recrystallization from isopropyl ether yielded 0.50 g of the titled compound as pink solids. the resulting mixture was heated to reflux removing water using a Dean-Stark apparatus for 11 h After cooling the reaction mixture was concentrated to dryness The residue was dissolved into ethyl acetate (100 ml) washed consecutively with saturated aqueous sodium bicarbonate solution (50 ml) and brine (50 ml) dried (magnesium sulfate) concentrated to dryness The residue was purified by column chromatography (silica gel, 165 g; n-hexane/ethyl acetate (3/2 to 1/1))

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

Procedure: To a 1-L three-neck flask, under a nitrogen gas stream, trans-cinnamic acid chloride (100 g, 0.60 mol), phenol (59.3 g, 0.63 mol), and THF (500 ml) were fed, and a THF solution (100 ml) of triethylamine (63.8 g, 0.63 mol) were added dropwise using a dripping funnel while being chilled with ice. After the completion of dropwise addition, 12-hour stirring was performed at room temperature, and the reaction solution was poured into water. The obtained white precipitate was filtered and dried under reduced pressure, and thereafter the yield was 135.5 g (yield rate of 99.9%). This was dissolved into approximately 200 ml of methanol by heating, and then cooled. As a result, white crystal was obtained (112.6 g, yield rate of 83.8%). Note that, the obtained crystal was confirmed to be a target trans-cinnamic acid phenyl ester by NMR structural analysis. while being chilled with ice After the completion of dropwise addition, 12-hour was performed at room temperature The obtained white precipitate was filtered dried under reduced pressure the yield was 135.5 g (yield rate of 99.9%) by heating cooled As a result, white crystal was obtained (112.6 g, yield rate of 83.8%)

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

Procedure: To a 1-L three-neck flask, under a nitrogen gas stream, trans-cinnamic acid chloride (100 g, 0.60 mol), phenol (59.3 g, 0.63 mol), and THF (500 ml) were fed, and a THF solution (100 ml) of triethylamine (63.8 g, 0.63 mol) were added dropwise using a dripping funnel while being chilled with ice. After the completion of dropwise addition, 12-hour stirring was performed at room temperature, and the reaction solution was poured into water. The obtained white precipitate was filtered and dried under reduced pressure, and thereafter the yield was 135.5 g (yield rate of 99.9%). This was dissolved into approximately 200 ml of methanol by heating, and then cooled. As a result, white crystal was obtained (112.6 g, yield rate of 83.8%). Note that, the obtained crystal was confirmed to be a target trans-cinnamic acid phenyl ester by NMR structural analysis. while being chilled with ice After the completion of dropwise addition, 12-hour was performed at room temperature The obtained white precipitate was filtered dried under reduced pressure the yield was 135.5 g (yield rate of 99.9%) by heating cooled As a result, white crystal was obtained (112.6 g, yield rate of 83.8%)

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

Procedure: To a stirred solution of 1 (36 mg, 0.09 mmol) and iPr2NEt (32 μl, 0.189 mmol) in CHCl3 (2 mL) was added [(2E)-3-phenylprop-2-enoyl]chloride (15 mg, 0.09 mmol). After 4 h the reaction mixture was washed with HCl (1 N) and sat. NaCl solution, and dried over MgSO4. The solvent was evaporated and the residue was filtered through silica gel using AcOEt/MeOH 1% as eluent to afford 159 as white solid (10 mg, 20%). M/Z APCI: 531.2 (M+1), 529.1 (M−1). Anal. HPLC: rt.=6.18 min (method a). After 4 h the reaction mixture was washed with HCl (1 N) and sat. NaCl solution dried over MgSO4 The solvent was evaporated the residue was filtered through silica gel

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

Procedure: To a stirred solution of 1 (36 mg, 0.09 mmol) and iPr2NEt (32 μl, 0.189 mmol) in CHCl3 (2 mL) was added [(2E)-3-phenylprop-2-enoyl]chloride (15 mg, 0.09 mmol). After 4 h the reaction mixture was washed with HCl (1 N) and sat. NaCl solution, and dried over MgSO4. The solvent was evaporated and the residue was filtered through silica gel using AcOEt/MeOH 1% as eluent to afford 159 as white solid (10 mg, 20%). M/Z APCI: 531.2 (M+1), 529.1 (M−1). Anal. HPLC: rt.=6.18 min (method a). After 4 h the reaction mixture was washed with HCl (1 N) and sat. NaCl solution dried over MgSO4 The solvent was evaporated the residue was filtered through silica gel

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

Procedure: The title compound was prepared following the procedure A using 4-phenylbutylamine, 4-[4-(chloromethyl)-1,3-thiazol-2-yl]benzoyl chloride, (2E)-3-phenylacryloyl chloride and methyl[4-(aminomethyl)phenoxy]acetate, acetate salt. M+(ESI): 660.1

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

Procedure: The title compound was prepared following the procedure A using 4-pentylbenzylamine, 2-(chloromethyl)-1,3-thiazole-4-carbonyl chloride, (2E)-3-phenylacryloyl chloride and 6-(aminomethyl)-2,2-dimethyl-4H-1,3-benzodioxin-4-one acetate. M+(ESI): 598.4

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

Procedure: The title compound was prepared following the procedure A using octylamine, 4-(chloromethyl)benzoyl chloride, (2E)-3-phenylacryloyl chloride and 6-(aminomethyl)-2,2-dimethyl-4H-1,3-benzodioxin-4-one acetate. M+(ESI): 543.5