2-methylprop-1-enylboronic acid

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of 2-(3-bromo-2-methylbenzoylamino)indan-2-carboxylic acid ethyl ester (293) (402 mg-1 mmol) and 2-methyl-1-propenylboronic acid (200 mg, 2 mmol, 2 eq) in dry DMF (20 mL) and saturated NaHCO3 (5 mL) is degassed for 10 min and then treated with tetrakis(triphenylphosphine)palladium(0) (400 mg). The mixture is stirred at 110° C. for 5 h. The reaction is cooled and the DMF removed in vacuo and the residue diluted with water (80 mL). The aqueous is filtered through celite and extracted with EtOAc (3×50 mL). The organic extracts are washed with water (2×30 mL) and brine (2×30 mL), and dried over MgSO4. The organic phase is then concentrated in vacuo and purified by flash chromatography (120 g silica gel, 30% EtOAc in heptane) to give pale yellow oil (350 mg, 92%). is degassed for 10 min treated with tetrakis(triphenylphosphine)palladium(0) (400 mg) The reaction is cooled the DMF removed in vacuo the residue diluted with water (80 mL) The aqueous is filtered through celite extracted with EtOAc (3×50 mL) The organic extracts are washed with water (2×30 mL) and brine (2×30 mL) dried over MgSO4 The organic phase is then concentrated in vacuo purified by flash chromatography (120 g silica gel, 30% EtOAc in heptane)

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of tert-butyl 9-bromo-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (328 mg, 1.00 mmol), 2,2-dimethylethenylboronic acid (98.0 mg, 1.00 mmol), saturated aqueous sodium carbonate solution (14 ml) and tetrakis(triphenylphosphine)palladium(0) (32.6 mg, 0.0282 mmol) in dimethoxyethane (10 ml) was stirred at 85° C. for 12 hr under a nitrogen atmosphere. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with water, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1) to give the desired product (270 mg, 89.1%) as an oil. the mixture was extracted with ethyl acetate The extract was washed with water dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure the residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1)

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Bromo-3-fluoro-6-nitrobenzonitrile (Example 134d) (0.62 g, 2.53 mmol), 2-methylprop-1-enylboronic acid (0.50 g, 5.05 mmol), palladium(II) acetate (0.023 g, 0.102 mmol), K3PO4 (1.61 g, 7.58 mmol), and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (0.083 g, 0.202 mmol) were suspended in anhydrous THF (16 mL) under nitrogen and heated at 70° C. for 4.5 h. Solvent was removed under vacuum, and the product was purified by chromatography on silica gel eluting with gradient 0% to 100% ethyl acetate in hexanes, to give 3-fluoro-2-(2-methylprop-1-enyl)-6-nitrobenzonitrile 0.44 g (78%) as a yellow solid. MS 221 (MH+). Solvent was removed under vacuum the product was purified by chromatography on silica gel eluting with gradient 0% to 100% ethyl acetate in hexanes

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of 2-cyano-3-nitrophenyl trifluoromethanesulfonate (Example 129d) (4.80 g; 16.21 mmol), 2-methyl-1-propenylboronic acid (2.43 g; 24.32 mmol), tetrakis(tiphenylphosphine)palladium(0) (1.87 g; 1.62 mmol), sodium carbonate (1.89 g; 17.83 mmol) and water (33.0 mL) in dimethoxyethane (DME) (132.0 mL) was heated at reflux for 4 h, under a nitrogen atmosphere. The reaction mixture was cooled to room temperature and diluted with water (100 mL) and EtOAc (250 mL). The organic phase was separated and the aqueous phase was extracted with EtOAc (3×100 mL). The combined extract was washed with brine and dried with anhydrous MgSO4. The filtrate was evaporated and the residue was purified by chromatography on silica gel using gradient hexanes to hexanes/EtOAc (7:3), to give 2.01 g (61%) of the title compound as a yellow solid. 1H-NMR (400 MHz, DMSO-d6) δ 8.19-8.23 (m, 1H), 7.83-7.93 (m, 2H), 6.45 (broad s, 1H), 1.95-1.98 (m, 3H), 1.75-1.79 (m, 3H). was heated at reflux for 4 h, under a nitrogen atmosphere The organic phase was separated the aqueous phase was extracted with EtOAc (3×100 mL) The combined extract was washed with brine dried with anhydrous MgSO4 The filtrate was evaporated the residue was purified by chromatography on silica gel using gradient hexanes to hexanes/EtOAc (7:3)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of 2-cyano-3-nitrophenyl trifluoromethanesulfonate (Example 129d) (4.80 g; 16.21 mmol), 2-methyl-1-propenylboronic acid (2.43 g; 24.32 mmol), tetrakis(tiphenylphosphine)palladium(0) (1.87 g; 1.62 mmol), sodium carbonate (1.89 g; 17.83 mmol) and water (33.0 mL) in dimethoxyethane (DME) (132.0 mL) was heated at reflux for 4 h, under a nitrogen atmosphere. The reaction mixture was cooled to room temperature and diluted with water (100 mL) and EtOAc (250 mL). The organic phase was separated and the aqueous phase was extracted with EtOAc (3×100 mL). The combined extract was washed with brine and dried with anhydrous MgSO4. The filtrate was evaporated and the residue was purified by chromatography on silica gel using gradient hexanes to hexanes/EtOAc (7:3), to give 2.01 g (61%) of the title compound as a yellow solid. 1H-NMR (400 MHz, DMSO-d6) δ 8.19-8.23 (m, 1H), 7.83-7.93 (m, 2H), 6.45 (broad s, 1H), 1.95-1.98 (m, 3H), 1.75-1.79 (m, 3H). was heated at reflux for 4 h, under a nitrogen atmosphere The organic phase was separated the aqueous phase was extracted with EtOAc (3×100 mL) The combined extract was washed with brine dried with anhydrous MgSO4 The filtrate was evaporated the residue was purified by chromatography on silica gel using gradient hexanes to hexanes/EtOAc (7:3)

反応条件: temp:12.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 5-(2-benzyloxy-4-iodophenyl)-1,1-dioxo-1,2,5-thiadiazolidin-3-one (150 mg, 0.338 mmol) and 2,2-dimethylethenylboronic acid (67 mg, 0.670 mmol), resin-bound PPh3Pd (519 mg, 0.069 mmol) and Na2CO3 (0.338 mL, 2M) in DME (3 mL) is heated in a microwave apparatus at 12° C. for 20 min. The mixture is filtered through Celite, washed with MeCN and concentrated. The residue is purified by reverse phase chromatography using a gradient of 10-60% EtOH/H2O as eluent to afford the title compound: (M−1)−=371. The mixture is filtered through Celite washed with MeCN concentrated The residue is purified by reverse phase chromatography

反応条件: temp:12.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 5-(2-benzyloxy-4-iodophenyl)-1,1-dioxo-1,2,5-thiadiazolidin-3-one (150 mg, 0.338 mmol) and 2,2-dimethylethenylboronic acid (67 mg, 0.670 mmol), resin-bound PPh3Pd (519 mg, 0.069 mmol) and Na2CO3 (0.338 mL, 2M) in DME (3 mL) is heated in a microwave apparatus at 12° C. for 20 min. The mixture is filtered through Celite, washed with MeCN and concentrated. The residue is purified by reverse phase chromatography using a gradient of 10-60% EtOH/H2O as eluent to afford the title compound: (M−1)−=371. The mixture is filtered through Celite washed with MeCN concentrated The residue is purified by reverse phase chromatography

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Bromo-3-fluoro-6-nitrobenzonitrile (Example 134d) (0.62 g, 2.53 mmol), 2-methylprop-1-enylboronic acid (0.50 g, 5.05 mmol), palladium(II) acetate (0.023 g, 0.102 mmol), K3PO4 (1.61 g, 7.58 mmol), and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (0.083 g, 0.202 mmol) were suspended in anhydrous THF (16 mL) under nitrogen and heated at 70° C. for 4.5 h. Solvent was removed under vacuum, and the product was purified by chromatography on silica gel eluting with gradient 0% to 100% ethyl acetate in hexanes, to give 3-fluoro-2-(2-methylprop-1-enyl)-6-nitrobenzonitrile 0.44 g (78%) as a yellow solid. MS 221 (MH+). Solvent was removed under vacuum the product was purified by chromatography on silica gel eluting with gradient 0% to 100% ethyl acetate in hexanes

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of 2-cyano-3-nitrophenyl trifluoromethanesulfonate (Example 129d) (4.80 g; 16.21 mmol), 2-methyl-1-propenylboronic acid (2.43 g; 24.32 mmol), tetrakis(tiphenylphosphine)palladium(0) (1.87 g; 1.62 mmol), sodium carbonate (1.89 g; 17.83 mmol) and water (33.0 mL) in dimethoxyethane (DME) (132.0 mL) was heated at reflux for 4 h, under a nitrogen atmosphere. The reaction mixture was cooled to room temperature and diluted with water (100 mL) and EtOAc (250 mL). The organic phase was separated and the aqueous phase was extracted with EtOAc (3×100 mL). The combined extract was washed with brine and dried with anhydrous MgSO4. The filtrate was evaporated and the residue was purified by chromatography on silica gel using gradient hexanes to hexanes/EtOAc (7:3), to give 2.01 g (61%) of the title compound as a yellow solid. 1H-NMR (400 MHz, DMSO-d6) δ 8.19-8.23 (m, 1H), 7.83-7.93 (m, 2H), 6.45 (broad s, 1H), 1.95-1.98 (m, 3H), 1.75-1.79 (m, 3H). was heated at reflux for 4 h, under a nitrogen atmosphere The organic phase was separated the aqueous phase was extracted with EtOAc (3×100 mL) The combined extract was washed with brine dried with anhydrous MgSO4 The filtrate was evaporated the residue was purified by chromatography on silica gel using gradient hexanes to hexanes/EtOAc (7:3)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Prepared as in Example 77a from N-(2-cyano-4-bromophenyl)sulfamide (Example 83b) and 2-methylprop-1-enylboronic acid.

反応条件: temp:0.00; pressure:0.00; stir: