2-bromo-3-phenylprop-2-enal

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: According to Procedure A above, 6-chloro-4-(piperidin-4-ylamino)-chromen-2-one and 2-bromo-3-phenyl-propenal (0.046 g, 0.216 mmol) were allowed to react to give the title compound (0.0088 g, 25.1%, mono-TFA salt) as a off-white solid. 1H NMR (400 MHz, MeOH) δ ppm 8.15 (d, J=4, 1H), 7.72 (dd, J=4, 8, 1H), 7.60 (dd, J=4, 8, 1H), 7.39-7.49 (m, 4H), 7.33 (d, J=8, 2H), 5.47 (s, 1H), 4.40 (s, 2H), 3.86-3.97 (m, 1H), 3.64-3.78 (m, 2H), 3.27-3.41 (partially buried m, 2H), 2.30-2.44 (m, 2H), 2.01-2.18 (m, 2H); MS (ESI+Q1MS) m/z 475 [M+H]+ to react

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

Procedure: According to Procedure A above, 6-chloro-4-(piperidin-4-ylamino)-chromen-2-one and 2-bromo-3-phenyl-propenal (0.046 g, 0.216 mmol) were allowed to react to give the title compound (0.0088 g, 25.1%, mono-TFA salt) as a off-white solid. 1H NMR (400 MHz, MeOH) δ ppm 8.15 (d, J=4, 1H), 7.72 (dd, J=4, 8, 1H), 7.60 (dd, J=4, 8, 1H), 7.39-7.49 (m, 4H), 7.33 (d, J=8, 2H), 5.47 (s, 1H), 4.40 (s, 2H), 3.86-3.97 (m, 1H), 3.64-3.78 (m, 2H), 3.27-3.41 (partially buried m, 2H), 2.30-2.44 (m, 2H), 2.01-2.18 (m, 2H); MS (ESI+Q1MS) m/z 475 [M+H]+ to react

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

Procedure: 1.33 g (10 mmol) cinnamaldehyde was dissolved in 5 mL glacial acetic acid and cooled on an ice-water bath. 1.62 g bromine was added, and anhydrous K2CO3 was then added, and it was stirred until no gas was evolving. After refluxing for 30 min, the reaction mixture was poured into 100 mL cold water with stirring, extracted with 50 mL ethyl ether three times. The combined ethyl ether layers were washed with water one time, saturated aqueous NaCl solution one time, dried over MgSO4 for 2 hours, filtrated, and the filtrate was dried under vacuum, and washed with anhydrous ethyl ether: petroleum ether (1:1) to give the title compound as light yellow powder. cooled on an ice-water bath After refluxing for 30 min with stirring extracted with 50 mL ethyl ether three times The combined ethyl ether layers were washed with water one time, saturated aqueous NaCl solution one time dried over MgSO4 for 2 hours filtrated the filtrate was dried under vacuum washed with anhydrous ethyl ether: petroleum ether (1:1)

Conditions: temp:22.01; pressure:0.00; stir:

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

Procedure: To a solution of 1,7-octadiyne (254.4 mg, 2.4 mmol) in dry THF (50 mL) cooled at −78° C. was added nBuLi (1.6 M in hexanes, 1.5 mL, 2.0 mmol) followed by stirring at the same temperature for 10 minutes. To the previously prepared lithium acetylide solution was added a solution of α-bromocinnamaldehyde Compound 1 (422.0 mg, 2.0 mmol) in dry THF (5 mL) and the resultant mixture was stirred at −78° C. for 15 minutes. The reaction was then quenched with saturated aqueous NH4Cl (20 mL) and extracted with EtOAc (50 mL×2). The combined organic layer was washed with brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, 14 percent EtOAc in hexane) to give 613.1 mg (97 percent) of Compound 7: pale yellow oil; Rf=0.33 (14 percent EtOAc in hexane); IR (neat) 3397 (br), 3294, 2944, 2864, 2232, 2116, 1492, 1430, 1064 cm−1; 1H NMR (300 MHz, CDCl3) δ7.65-7.61 (m, 2H), 7.40-7.29 (m, 3H), 7.24 (s, 1H), 5.07 (br s, 1H), 2.68 (d, J=6.18 Hz, 1H, exchangeable with D2O), 2.34-2.27 (m, 2H), 2.26-2.19 (m, 2H), 1.96 (t, J=2.67 Hz, 1H), 1.74-1.62 (m, 4H); 13C NMR (75 MHz, CDCl3) δ135.4, 129.8, 129.1, 128.9, 126.8, 88.3, 84.8, 79.0, 69.4, 69.3, 61.2, 28.1, 27.9, 19.0, 18.6; MS (+CI) m/z (relative intensity) 318 (M+, 81Br, 4), 316 (M+, 79Br, 4), 220 (100). The reaction was then quenched with saturated aqueous NH4Cl (20 mL) extracted with EtOAc (50 mL×2) The combined organic layer was washed with brine dried over anhydrous MgSO4 filtered concentrated under reduced pressure The residue was purified by flash column chromatography (silica gel, 14 percent EtOAc in hexane)

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

Procedure: To a solution of Pd(PPh3)4 (0.55 g, 0.24 mmol) and α-bromocinnamaldehyde Compound 1 (2.08 g, 4.74 mmol) in degassed THF (170 mL) cooled in an ice-water bath was added a solution of 1,7-octadiyne (2.23 g, 9.48 mmol), triethylamine (15 mL), and CuI (0.36 g, 0.95 mmol) in degassed THF (30 mL) via a syringe under a nitrogen atmosphere. The reaction flask was then covered by a sheet of aluminum foil. After stirring at room temperature for 8 hours the reaction was quenched with saturated aqueous NH4Cl (50 mL) and diluted with EtOAc (100 mL). The organic layer was washed with brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, 10 percent EtOAc in hexane) to give 2.13 g (91 percent) of Compound 2: yellow oil; Rf=0.50 (15 percent EtOAc in hexane); IR (neat) 3294, 2944, 2230, 2116, 1692, 1598, 1450, 1324, 1180 cm−1; 1H NMR (300 MHz, CDCl3) δ9.56 (s, 1H), 8.11-8.07 (m, 2H), 7.48-7.43 (m, 3H), 7.43 (s, 1H), 2.60 (t, J=6.65 Hz, 2H), 2.27 (td, J=6.78, 2.64 Hz, 2H), 1.97 (t, J=2.64 Hz, 1H), 1.86-1.69 (m, 4H); 13C NMR (75 MHz, CDCl3) δ192.4, 151.8, 134.9, 132.0, 131.1, 129.4, 124.1, 103.4, 84.6, 75.4, 69.4, 28.2, 28.0, 20.3, 18.7; MS (+FAB) m/z (relative intensity) 237 (M+H+, 100). was quenched with saturated aqueous NH4Cl (50 mL) diluted with EtOAc (100 mL) The organic layer was washed with brine dried over anhydrous MgSO4 filtered concentrated in vacuo The residue was purified by flash column chromatography (silica gel, 10 percent EtOAc in hexane)

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: According to Procedure A above, 6-chloro-4-(piperidin-4-ylamino)-chromen-2-one and 2-bromo-3-phenyl-propenal (0.046 g, 0.216 mmol) were allowed to react to give the title compound (0.0088 g, 25.1%, mono-TFA salt) as a off-white solid. 1H NMR (400 MHz, MeOH) δ ppm 8.15 (d, J=4, 1H), 7.72 (dd, J=4, 8, 1H), 7.60 (dd, J=4, 8, 1H), 7.39-7.49 (m, 4H), 7.33 (d, J=8, 2H), 5.47 (s, 1H), 4.40 (s, 2H), 3.86-3.97 (m, 1H), 3.64-3.78 (m, 2H), 3.27-3.41 (partially buried m, 2H), 2.30-2.44 (m, 2H), 2.01-2.18 (m, 2H); MS (ESI+Q1MS) m/z 475 [M+H]+ to react

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

Procedure: 1.33 g (10 mmol) cinnamaldehyde was dissolved in 5 mL glacial acetic acid and cooled on an ice-water bath. 1.62 g bromine was added, and anhydrous K2CO3 was then added, and it was stirred until no gas was evolving. After refluxing for 30 min, the reaction mixture was poured into 100 mL cold water with stirring, extracted with 50 mL ethyl ether three times. The combined ethyl ether layers were washed with water one time, saturated aqueous NaCl solution one time, dried over MgSO4 for 2 hours, filtrated, and the filtrate was dried under vacuum, and washed with anhydrous ethyl ether: petroleum ether (1:1) to give the title compound as light yellow powder. cooled on an ice-water bath After refluxing for 30 min with stirring extracted with 50 mL ethyl ether three times The combined ethyl ether layers were washed with water one time, saturated aqueous NaCl solution one time dried over MgSO4 for 2 hours filtrated the filtrate was dried under vacuum washed with anhydrous ethyl ether: petroleum ether (1:1)