[(E)-prop-1-烯基]硼酸

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 6-Amino-5-bromo-2-(4-chloro-2-fluoro-3-methoxyphenyl)-pyrimidine-4-carboxylic acid methyl ester (400 mg, 1.02 mmol), trans-propenyl boronic acid (2132 mg, 1.54 mmol), bis(triphenylphosphine)palladium(II) dichloride (72 mg, 0.1 mmol), and cesium fluoride (311 mg, 2.05 mmol) were combined in 1,2-dimethoxyethane (2 mL) and water (2 mL) and heated at 100° C. for 15 min in a CEM microwave reactor. The cooled reaction mixture was partitioned between ethyl acetate and water; and the organic phase was dried and concentrated. The product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient) then purified again by reverse phase HPLC to yield the title compound: mp 133-135° C.: 1H NMR (CDCl3) δ 7.63 (m, 1H), 7.22 (m, 1H), 6.43 (m, 1H), 6.12 (m, 1H), 5.35 (br s, 2H), 3.99 (d, 3H), 3.94 (s, 3H), 1.94 (dd, 3H). The cooled reaction mixture was partitioned between ethyl acetate and water and the organic phase was dried concentrated The product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient) then purified again by reverse phase HPLC

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 6-Amino-5-bromo-2-(4-chloro-2-fluoro-3-methoxyphenyl)-pyrimidine-4-carboxylic acid methyl ester (400 mg, 1.02 mmol), trans-propenyl boronic acid (2132 mg, 1.54 mmol), bis(triphenylphosphine)palladium(II) dichloride (72 mg, 0.1 mmol), and cesium fluoride (311 mg, 2.05 mmol) were combined in 1,2-dimethoxyethane (2 mL) and water (2 mL) and heated at 100° C. for 15 min in a CEM microwave reactor. The cooled reaction mixture was partitioned between ethyl acetate and water; and the organic phase was dried and concentrated. The product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient) then purified again by reverse phase HPLC to yield the title compound: mp 133-135° C.: 1H NMR (CDCl3) δ 7.63 (m, 1H), 7.22 (m, 1H), 6.43 (m, 1H), 6.12 (m, 1H), 5.35 (br s, 2H), 3.99 (d, 3H), 3.94 (s, 3H), 1.94 (dd, 3H). The cooled reaction mixture was partitioned between ethyl acetate and water and the organic phase was dried concentrated The product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient) then purified again by reverse phase HPLC

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Trans-1-propen-1-ylboronic acid (0.103 g, 1.20 mmol, 3.0 eq.), triethylamine (0.220 ml, 1.60 mmol, 4.0 eq.) and mono triflate 13 (0.500 g, 0.401 mmol, 1.0 eq.) were dissolved in a mixture of ethanol (10 mL), toluene (20 mL) and water (3 mL) under a nitrogen atmosphere. The reaction mixture was degassed under nitrogen for 5 minutes and tetrakis(triphenylphosphine)palladium(0) (0.018 g, 0.016 mmol, 0.04 eq.) added. The reaction mixture was stirred at 60° C. for 50 minutes, then concentrated to dryness under reduced pressure and the crude solid was purified by flash chromatography (silica gel, 50:50 acetate/hexane v/v then 66:33 ethyl acetate/hexane v/v) to afford the product as pale yellow solid. (0.35 g, 77%). LC/MS (3.910 min (ES+)), m/z: 1137.86 [M+H]+. The reaction mixture was degassed under nitrogen for 5 minutes concentrated to dryness under reduced pressure the crude solid was purified by flash chromatography (silica gel, 50:50 acetate/hexane v/v

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2-iodo-3-methyl-benzoic acid (708 mg, 2.70 mmol) and trans-1-propen-1-ylboronic acid (526 mg, 6.12 mmol) in EtOH (10 mL) is added palladium anchored homogeneous catalyst, FibreCatPd(0) (4.84% Pd, 235 mg, 0.15 mmol) and 2M aqueous solution of K2SO4 (3.06 mL, 6.12 mmol). The resulting reaction mixture is covered with argon and run in a microwave reaction: 110° C., 7 h. After concentration in vacuo, the residue is purified by HPLC to give a pure product (162) as a pale yellow solid (500 mg, 93%). The resulting reaction mixture run in a microwave reaction 110° C., 7 h After concentration in vacuo the residue is purified by HPLC

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2-iodo-3-methyl-benzoic acid (708 mg, 2.70 mmol) and trans-1-propen-1-ylboronic acid (526 mg, 6.12 mmol) in EtOH (10 mL) is added palladium anchored homogeneous catalyst, FibreCatPd(0) (4.84% Pd, 235 mg, 0.15 mmol) and 2M aqueous solution of K2SO4 (3.06 mL, 6.12 mmol). The resulting reaction mixture is covered with argon and run in a microwave reaction: 110° C., 7 h. After concentration in vacuo, the residue is purified by HPLC to give a pure product (162) as a pale yellow solid (500 mg, 93%). The resulting reaction mixture run in a microwave reaction 110° C., 7 h After concentration in vacuo the residue is purified by HPLC

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 5-fluoro-2-(2-iodo-3-methyl-benzoylamino)-indan-2-carboxylic acid ethyl ester (400 mg, 0.85 mmol) and trans-1-propen-1-ylboronic acid (294 mg, 3.42 mmol) in EtOH (10 mL) and dioxane (5 mL) is added palladium anchored homogeneous catalyst, FibreCatPd(0) (4.84% Pd, 186 mg, 8.5% mmol) and 2M aqueous solution of K2SO4 (1.71 mL, 3.42 mmol). The resulting reaction mixture is covered with argon and run in a microwave reaction: 110° C., 7 h. After concentration in vacuo, the residue is purified by HPLC to give a pure product (153) as white solid (165 mg, 51%). The resulting reaction mixture run in a microwave reaction 110° C., 7 h After concentration in vacuo the residue is purified by HPLC

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2-(2-iodo-3-methyl-benzoylamino)-indan-2-carboxylic acid ethyl ester (600 mg, 1.34 mmol) and trans-1-propen-1-ylboronic acid (460 mg, 5.36 mmol) in EtOH (10 mL) and dioxane (10 mL) is added palladium anchored homogeneous catalyst, FibreCatPd(0), (4.84% Pd, 285 mg, 0.13 mmol) and 2M aqueous solution of K2SO4 (2.68 mL, 5.36 mmol). The resulting reaction mixture is covered with argon and run in a microwave reaction: 110° C., 8 h. After concentration in vacuo, the residue is purified by HPLC and gave the pure product (142) as white solid (300 mg, 63%). The resulting reaction mixture run in a microwave reaction 110° C., 8 h After concentration in vacuo the residue is purified by HPLC

反应条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 400 mg (1.1 mmol) 2-chloro-N-[(3-fluorophenyl)-methyl]-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide in toluene (15 ml) were added 140 mg (1.7 mmol) (E)-prop-1-enylboronic acid, 1.1 g (3.3 mmol) CsCO3 and EtOH (1.5 ml). After degassing with argon for 15 min 370 mg (0.32 mmol) Pd(PPh3)4 were added and the RM was heated to 110° C. for 5 h. Subsequently the RM was filtered through celite and the filtrate was concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 3:1) provided 300 mg (0.8 mmol, 74%) (E)-N-(3-fluorobenzyl)-4-methyl-6-morpholino-2-(prop-1-enyl)-pyridine-3-carboxylic acid amide (example 9). [M+H]+ 370.2. were added Subsequently the RM was filtered through celite the filtrate was concentrated in vacuo Purification of the residue by CC (hexane/EtOAc 3:1)

反应条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 400 mg (1.1 mmol) 2-chloro-N-[(3-fluorophenyl)-methyl]-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide in toluene (15 ml) were added 140 mg (1.7 mmol) (E)-prop-1-enylboronic acid, 1.1 g (3.3 mmol) CsCO3 and EtOH (1.5 ml). After degassing with argon for 15 min 370 mg (0.32 mmol) Pd(PPh3)4 were added and the RM was heated to 110° C. for 5 h. Subsequently the RM was filtered through celite and the filtrate was concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 3:1) provided 300 mg (0.8 mmol, 74%) (E)-N-(3-fluorobenzyl)-4-methyl-6-morpholino-2-(prop-1-enyl)-pyridine-3-carboxylic acid amide (example 9). [M+H]+ 370.2. were added Subsequently the RM was filtered through celite the filtrate was concentrated in vacuo Purification of the residue by CC (hexane/EtOAc 3:1)

反应条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 400 mg (1.1 mmol) 2-chloro-N-[(3-fluorophenyl)-methyl]-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide in toluene (15 ml) were added 140 mg (1.7 mmol) (E)-prop-1-enylboronic acid, 1.1 g (3.3 mmol) CsCO3 and EtOH (1.5 ml). After degassing with argon for 15 min 370 mg (0.32 mmol) Pd(PPh3)4 were added and the RM was heated to 110° C. for 5 h. Subsequently the RM was filtered through celite and the filtrate was concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 3:1) provided 300 mg (0.8 mmol, 74%) (E)-N-(3-fluorobenzyl)-4-methyl-6-morpholino-2-(prop-1-enyl)-pyridine-3-carboxylic acid amide (example 9). [M+H]+ 370.2. were added Subsequently the RM was filtered through celite the filtrate was concentrated in vacuo Purification of the residue by CC (hexane/EtOAc 3:1)

反应条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of tert-butyl 9-bromo-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (400 mg, 1.22 mmol), trans-1-propen-1-ylboronic acid (157 mg, 1.82 mmol), ethanol (1.4 ml), 2N aqueous sodium carbonate solution (5 ml), and tetrakis(triphenylphosphine)palladium(0) (170 mg, 0.147 mmol) in toluene (10 ml) was stirred under a nitrogen atmosphere at 95° C. for 12 hr. 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=2:1) to give the desired product (340 mg, 97.1%) 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=2:1)

反应条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of tert-butyl 9-bromo-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (400 mg, 1.22 mmol), trans-1-propen-1-ylboronic acid (157 mg, 1.82 mmol), ethanol (1.4 ml), 2N aqueous sodium carbonate solution (5 ml), and tetrakis(triphenylphosphine)palladium(0) (170 mg, 0.147 mmol) in toluene (10 ml) was stirred under a nitrogen atmosphere at 95° C. for 12 hr. 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=2:1) to give the desired product (340 mg, 97.1%) 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=2:1)