(2-but-3-enylphenyl)boronic acid

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (2S)-methyl 2-(7-(4-allyl-5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.092 g, 0.143 mmol), (2-(but-3-en-1-yl)phenyl)boronic acid (0.050 g, 0.286 mmol) and 2.0 M aq. Na2CO3 (0.179 mL, 0.358 mmol) in DMF (4 mL) was sparged with nitrogen for 10 min, treated with Pd(Ph3P)4 (0.012 g, 10.01 μmol), sparged for 5 min, then heated (90° C.) for 5 h. The reaction was cooled, then diltued with EtOAc (20 mL) and washed with water (10 mL) and brine (10 mL). The organic layer was dried (Na2SO4), filtered, and concentrated and the residue was purified by biotage (Isco 4 g SiO2, 0% (5 CV), 0-60% (20 CV), 60% (5 CV), EtOAc in hexanes) to afford the desired product (0.099 g, 0.143 mmol, 100% yield). LCMS (M+H)=691.4. sparged for 5 min The reaction was cooled washed with water (10 mL) and brine (10 mL) The organic layer was dried (Na2SO4) filtered concentrated the residue was purified by biotage (Isco 4 g SiO2, 0% (5 CV), 0-60% (20 CV), 60% (5 CV), EtOAc in hexanes)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (2S)-methyl 2-(7-(4-allyl-7-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.028 g, 0.045 mmol), (2-(but-3-en-1-yl)phenyl)boronic acid (0.016 g, 0.090 mmol) and 2.0 M aq. Na2CO3 (0.056 ml, 0.113 mmol) in dry DMF (2.5 ml) was sparged with N2 for 15 min, then treated with Pd(Ph3P)4 (3.7 mg, 3.2 μmol), sparged for another 5 min, then heated (90° C.) for 16 h. The reaction was cooled, filtered (0.45 μm syringe tip filter), and purified by prep-HPLC to afford the desired product. 1H NMR (500 MHz, CDCl3) δ 7.88 (dt, J=7.9, 1.3 Hz, 1H), 7.83 (t, J=1.5 Hz, 1H), 7.44 (t, J=7.6 Hz, 1H), 7.32-7.36 (m, 2H), 7.29-7.31 (m, 1H), 7.26-7.28 (m, 2H), 6.88 (s, 1H), 6.81 (s, 1H), 6.64 (s, 1H), 5.65-5.85 (m, 2H), 5.21 (dd, J=17.2, 1.6 Hz, 1H), 5.10-5.15 (m, 2H), 4.85-4.94 (m, 2H), 4.33-4.38 (m, 2H), 3.78-3.86 (m, 1H), 3.68-3.76 (m, 1H), 3.67 (s, 3H), 3.23-3.40 (m, 2H), 2.78 (s, 3H), 2.66-2.74 (m, 2H), 2.26 (td, J=7.9, 6.7 Hz, 2H), 1.92 (s, 3H), 1.20 (s, 9H). LCMS (M+H)=671.5. sparged for another 5 min The reaction was cooled filtered (0.45 μm syringe tip filter) purified by prep-HPLC

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

Procedure: Ref Li, W., Nelson, D. P., Jensen, M. S., Hoerrner, R. S., Cai, D., Larsen, R. D., Reider, P. J. J. Org. Chem., 2002, 67, 5394-5397. A solution of 1-bromo-2-(but-3-en-1-yl)benzene (9.46 g, 44.8 mmol) in dry THF (44.8 ml) was cooled (−78° C.) and treated with 2.5 M n-BuLi in hexanes (19.7 ml, 49.3 mmol). The mixture was stirred for 20 min, and then treated with triisopropyl borate (51.5 ml, 224 mmol). After 90 min, the reaction mixture was warmed to room temperature over 1 h. Then, the reaction was quenched with 2.0 N aq. HCl (240 mL), diluted with Et2O (120 mL), and the layers were stirred vigorously for several minutes. The resulting white precipitate was removed by filtration and then the filtrate layers were separated. The organic layer was dried (Na2SO4), filtered, and concentrated, affording a pale yellow oil which partially solidified upon standing. These solids were triturated with hexanes and then dried under vacuum. The decantate was concentrated to an oil, dissolved in fresh hexanes (˜15 mL) and stored (−40° C.) for 16 h. A second crop of solid was collected, washing with a small volume of hexanes, and dried under vacuum Both crops were combined to afford the desired product (5.46 g, 31.0 mmol, 69.2% yield) as a white crystalline solid. 1H NMR (500 MHz, CDCl3) δ 8.24 (dd, J=7.8, 1.3 Hz, 1H), 7.52 (td, J=7.5, 1.4 Hz, 1H), 7.30-7.36 (m, 2H), 5.96 (ddt, J=17.0, 10.3, 6.5 Hz, 1H), 5.04-5.10 (m, 1H), 5.02 (dd, J=10.2, 1.6 Hz, 1H), 3.29-3.40 (m, 2H), 2.50 (td, J=7.9, 6.6 Hz, 2H). LCMS (M−H)=175.11. After 90 min Then, the reaction was quenched with 2.0 N aq. HCl (240 mL) diluted with Et2O (120 mL) the layers were stirred vigorously for several minutes The resulting white precipitate was removed by filtration the filtrate layers were separated The organic layer was dried (Na2SO4) filtered concentrated affording a pale yellow oil which These solids were triturated with hexanes dried under vacuum The decantate was concentrated to an oil dissolved in fresh hexanes (˜15 mL) (−40° C.) for 16 h A second crop of solid was collected washing with a small volume of hexanes dried under vacuum Both crops