2-phenylethylboronic acid

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

Procedure: Reaction and post treatment were carried out in the same manner as in Reference example 18-(c) except for using 855 mg (1.80 mmol) of 3-bromo-1,5-bis(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in Reference example 20-(a) in place of 3-iodo-1,5-bis(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo-[2,3-d]pyridazin-4-one, and using 965 mg (6.43 mmol) of phenethylboronic acid in place of methylboronic acid, respectively, whereby 698 mg of the title compound was obtained as an orange oil. (Yield: 78%) Reaction and post treatment

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 2-5 mL microwave vial fitted with a stirbar was added methyl 6-bromoquinoline-3-carboxylate (0.25 g, 0.94 mmol), phenethylboronic acid (0.282 g, 1.88 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (0.0773 g, 0.094 mmol), and potassium carbonate (0.39 g, 2.82 mmol). The vial was capped and 1,4-dioxane (4 mL) and water (1 mL). The contents of the vial were heated in a microwave at 130° C. for 0.5 h. The vial was cooled to room temperature and opened. The contents were partitioned between ethyl acetate and water. The phases were separated and the aqueous phase was extracted twice with ethyl acetate. The extracts were combined, washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (hexanes to 75/25 hexanes/ethyl acetate gradient) to afford the desired product (0.125 g, 36%). LC-MS: (FA) ES+ 292. To a 2-5 mL microwave vial fitted with a stirbar The vial was capped The vial was cooled to room temperature The contents were partitioned between ethyl acetate and water The phases were separated the aqueous phase was extracted twice with ethyl acetate washed with brine dried over sodium sulfate filtered concentrated under reduced pressure The crude residue was purified by silica gel chromatography (hexanes to 75/25 hexanes/ethyl acetate gradient)

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

Procedure: A mixture of 1-(5-(benzylcarbamoyl)-4-methylthiophen-2-yl)-2-oxo-1,2-dihydropyridin-4-yl trifluoromethanesulfonate (0.15 g, 0.32 mmol), phenethyl boronic acid (0.047 g, 0.31 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), 1:1 complex with dichloromethane (0.023 g, 0.028 mmol) and potassium carbonate (0.13 g, 0.95 mmol) in tetrahydrofuran (3 mL) and water (0.3 mL) was stirred in a sealed tube at 70° C. for 16 hours under nitrogen atmosphere. The reaction mixture was allowed to cool to ambient temperature, and was partitioned between ethyl acetate (75 mL) and water (35 mL). The organic layer was washed sequentially with 10% aqueous hydrochloric acid (30 mL), saturated aqueous sodium bicarbonate solution (2×25 mL) and brine (30 mL), then dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with 20% ethyl acetate in dichloromethane to afford the title compound as a light cream color solid in 40% yield (0.054 g): mp 145-146° C.; 1H NMR (300 MHz, CDCl3) δ 7.59 (d, J=7.3 Hz, 1H), 7.38-7.15 (m, 10H), 6.89 (s, 1H), 6.48 (s, 1H), 6.19 (t, J=5.8 Hz, 1H), 6.16 (dd, J=7.3, 1.9 Hz, 1H), 4.59 (d, J=5.8 Hz, 2H), 2.96-2.87 (m, 2H), 2.84-2.75 (m, 2H), 2.54 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 162.9, 160.7, 154.3, 140.1, 139.54, 139.5, 137.9, 133.2, 128.7, 128.6, 128.3, 127.8, 127.6, 127.2, 126.4, 121.8, 119.2, 109.3, 43.9, 36.9, 35.1, 15.9; MS (ES+) m/z 429.3 (M+1). to cool to ambient temperature was partitioned between ethyl acetate (75 mL) and water (35 mL) The organic layer was washed sequentially with 10% aqueous hydrochloric acid (30 mL), saturated aqueous sodium bicarbonate solution (2×25 mL) and brine (30 mL) dried over sodium sulfate filtered concentrated in vacuo The residue was purified by column chromatography eluted with 20% ethyl acetate in dichloromethane