肉桂基氯

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

实验步骤: Following general procedure B2 and D1, 3-(2,4-Dimethoxy-benzyloxy)-1H-benzo[4,5]furo[3,2-d]pyrimidine-2,4-dione was alkylated with trans-cinnamyl chloride and subsequently deprotected to provide the title compound as a white solid. 1H NMR (d6-DMSO, 300 MHz) δ 5.09 (s, 1H); 5.11 (s, 1H); 6.49-6.58 (m, 2H); 7.18-7.30 (m, 3H); 7.37-7.47 (m, 3H); 7.64 (dd, J=8 Hz, 1H); 7.82 (d, J=8 Hz, 1H); 8.07 (d, J=8 Hz, 1H), 10.73 (br s, 1H); Ret. time=2.66 min, m/z=333.0.

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

实验步骤: Following general procedure B2 and D1, 3-(2,4-Dimethoxy-benzyloxy)-1H-benzo[4,5]thieno[3,2-d]pyrimidine-2,4-dione was alkylated with trans-cinnamyl chloride and subsequently deprotected to provide the title compound as a white solid. 1H NMR (d6-DMSO, 300 MHz) δ 5.24 (s, 1H); 5.25 (s, 1H); 6.51-6.67 (m, 2H); 7.21 (dd, J=7 Hz, 1H); 7.28 (dd, J=8 Hz, 2H); 7.40 (d, J=7 Hz, 2H); 7.53 (dd, J=8 Hz, 1H); 7.61 (dd, J=8 Hz, 1H); 8.16 (d, J=8 Hz, 1H); 8.25 (d, J=8 Hz, 1H), 11.00 (br s, 1H); Ret. time=2.79 min., m/z=350.0.

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

实验步骤: To 3 mL of an N,N-dimethylformamide solution containing 0.10 g of ethyl 4-(3-(7-methoxy-2-oxo-1,2-dihydroquinolin-1-yl)propyl)piperidine-4-carboxylate, 0.11 g of potassium carbonate, 41 μL of ((1E)-3-chloro-1-propenyl)benzene and 45 mg of potassium iodide were added at room temperature and stirred for 4.5 hours. To the reaction mixture, water and ethyl acetate were added. The organic layer was separated, washed with aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [eluent; chloroform:methanol=35:1], to give 0.11 g of ethyl 4-(3-(7-methoxy-2-oxoquinolin-1(2H)-yl)propyl)-1-((2E)-3-phenyl-2-propen-1-yl)piperidine-4-carboxylate as a yellow oil. were added at room temperature The organic layer was separated washed with aqueous saturated sodium chloride solution dried over anhydrous magnesium sulfate the solvent was removed under reduced pressure The residue thus obtained was purified by silica gel column chromatography [eluent; chloroform:methanol=35:1]

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

实验步骤: To 3 mL of an N,N-dimethylformamide solution containing 0.10 g of ethyl 4-(3-(7-methoxy-2-oxo-1,2-dihydroquinolin-1-yl)propyl)piperidine-4-carboxylate, 0.11 g of potassium carbonate, 41 μL of ((1E)-3-chloro-1-propenyl)benzene and 45 mg of potassium iodide were added at room temperature and stirred for 4.5 hours. To the reaction mixture, water and ethyl acetate were added. The organic layer was separated, washed with aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [eluent; chloroform:methanol=35:1], to give 0.11 g of ethyl 4-(3-(7-methoxy-2-oxoquinolin-1(2H)-yl)propyl)-1-((2E)-3-phenyl-2-propen-1-yl)piperidine-4-carboxylate as a yellow oil. were added at room temperature The organic layer was separated washed with aqueous saturated sodium chloride solution dried over anhydrous magnesium sulfate the solvent was removed under reduced pressure The residue thus obtained was purified by silica gel column chromatography [eluent; chloroform:methanol=35:1]

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

实验步骤: A stirred mixture of 4-hydroxy-alpha-oxobenzeneacetic acid methyl ester (0.724 g) in dimethylformamide (10 mL) under argon was treated with 55% sodium hydride (0.175 g), stirred for 15 minutes and treated with (E)-(3-chloro-1-propenyl)benzene (0.763 g). The mixture was heated at 60° C. overnight and worked up as in Example 20. The material was purified by HPLC (dichloromethane-hexane; 3:1) and crystallized from diethyl etherhexane to provide 0.8 g of (E)-alpha-oxo-4-[(3-phenyl-2-propenyl)oxy]benzeneacetic acid methyl ester 0.1 molar hydrate, mp 80°-82° C. The material was purified by HPLC (dichloromethane-hexane; 3:1) crystallized from diethyl etherhexane

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

实验步骤: A stirred mixture of 4-hydroxy-alpha-oxobenzeneacetic acid methyl ester (0.724 g) in dimethylformamide (10 mL) under argon was treated with 55% sodium hydride (0.175 g), stirred for 15 minutes and treated with (E)-(3-chloro-1-propenyl)benzene (0.763 g). The mixture was heated at 60° C. overnight and worked up as in Example 20. The material was purified by HPLC (dichloromethane-hexane; 3:1) and crystallized from diethyl etherhexane to provide 0.8 g of (E)-alpha-oxo-4-[(3-phenyl-2-propenyl)oxy]benzeneacetic acid methyl ester 0.1 molar hydrate, mp 80°-82° C. The material was purified by HPLC (dichloromethane-hexane; 3:1) crystallized from diethyl etherhexane

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

实验步骤: A stirred mixture of 4-hydroxy-alpha-oxobenzeneacetic acid methyl ester (0.724 g) in dimethylformamide (10 mL) under argon was treated with 55% sodium hydride (0.175 g), stirred for 15 minutes and treated with (E)-(3-chloro-1-propenyl)benzene (0.763 g). The mixture was heated at 60° C. overnight and worked up as in Example 20. The material was purified by HPLC (dichloromethane-hexane; 3:1) and crystallized from diethyl etherhexane to provide 0.8 g of (E)-alpha-oxo-4-[(3-phenyl-2-propenyl)oxy]benzeneacetic acid methyl ester 0.1 molar hydrate, mp 80°-82° C. The material was purified by HPLC (dichloromethane-hexane; 3:1) crystallized from diethyl etherhexane

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

实验步骤: To 3 mL of an N,N-dimethylformamide solution containing 0.10 g of ethyl 4-(3-(7-methoxy-2-oxo-1,2-dihydroquinolin-1-yl)propyl)piperidine-4-carboxylate, 0.11 g of potassium carbonate, 41 μL of ((1E)-3-chloro-1-propenyl)benzene and 45 mg of potassium iodide were added at room temperature and stirred for 4.5 hours. To the reaction mixture, water and ethyl acetate were added. The organic layer was separated, washed with aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [eluent; chloroform:methanol=35:1], to give 0.11 g of ethyl 4-(3-(7-methoxy-2-oxoquinolin-1(2H)-yl)propyl)-1-((2E)-3-phenyl-2-propen-1-yl)piperidine-4-carboxylate as a yellow oil. were added at room temperature The organic layer was separated washed with aqueous saturated sodium chloride solution dried over anhydrous magnesium sulfate the solvent was removed under reduced pressure The residue thus obtained was purified by silica gel column chromatography [eluent; chloroform:methanol=35:1]

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

实验步骤: Prepared from compound 1 and 3-phenyl-2-[trans]propenylchloride as described for compound 78. Purified by chromatography (dichloromethane). Crystallized from diethyl ether at -20° C. M.p. 76°-79° C. Purified by chromatography (dichloromethane) Crystallized from diethyl ether at -20° C

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

实验步骤: 4-Fluoro-2-nitrophenol (13.5 g, 86 mmol) was dissolved in anhydrous DMF (100 mL) under an N2 atmosphere and treated sequentially with K2CO3 (23.7 g, 172 mmol) and trans-cinnamyl chloride (13.4 g, 87.6 mmol) and heated to 60° C. for 12 h. Upon completion, the reaction was diluted with EtOAc (500 mL), and washed with H2O (3×300 mL) and sat. aq. NaCl (500 mL). The organic layer was dried with MgSO4, filtered and concentrated to yield a yellow solid which was easily recrystallized from EtOAc/hexanes to provide pure 4-fluoro-2-nitrophenyl (2E)-3-phenylprop-2-enyl ether (5-1). 1H NMR (300 MHz, CDCl3) δ 7.61 (dd, J=7.5, 2.5 Hz, 1H), 7.41 (app d, J=7.0 Hz, 2H), 7.34 (t, J=7.5 Hz, 2H), 7.27 (m, 2H), 7.12 (dd, J=9.0, 4.0 Hz, 1H), 6.76 (d, J=16.0 Hz, 1H), 6.37 (dt, J=16.0, 5.5 Hz, 1H), 4.83 (dd, J=5.5, 1.0 Hz, 2H). washed with H2O (3×300 mL) and sat. aq. NaCl (500 mL) The organic layer was dried with MgSO4 filtered concentrated to yield a yellow solid which was easily recrystallized from EtOAc/hexanes

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

实验步骤: Into a dichloromethane solution of a poly(propyleneimine)dendrimer (1.0 g, 3.2 mmol, made by Aldrich Corporation) of the first generation (n=1 in FIG. 8) containing a catalytic quantity of triethylamine, a solution of trans-cinnamyl chloride (0.63 g, 3.7 mmol, made by Aldrich Corporation) was dropped, and the resultant solution was stirred at 0° C. for one hour and then at room temperature for 40 hours. This reaction liquid was diluted with dichloromethane, was cleaned sequentially with ion-exchange water, an aqueous solution of sodium carbonate and an aqueous solution of sodium chloride, and was dried with magnesium sulfate. After filtration, dichloromethane was removed by an evaporator. The crude product was dialyzed and reprecipitated repetitively for three times, and was dried under a reduced pressure. Then, a white solid was obtained. This reaction liquid an aqueous solution of sodium carbonate and an aqueous solution of sodium chloride, and was dried with magnesium sulfate After filtration, dichloromethane was removed by an evaporator The crude product was dialyzed reprecipitated repetitively for three times was dried under a reduced pressure Then, a white solid was obtained

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

实验步骤: 4-[2-(3-Aminophenyl)-6-(methyloxy)pyrazolo[1,5-a]pyridin-3-yl]-N-(3-{[2-(dimethylamino)ethyl]oxy}phenyl)-2-pyrimidinamine (97 mg, 0.20 mmol) and (2E)-3-phenyl-2-propenyl chloride (40 mg, 0.24 mmol) were combined in THF (2 mL) and stirred for 1 h. The mixture was diluted with DCM and TEA (2 drops), absorbed onto silica gel, and purified by silica gel chromatography to afford the title compound as a yellow solid (56 mg, 45%). 1H NMR (400 MHz, DMSO-d6) δ 10.34 (s, 1H), 9.55 (s, 1H), 8.57 (d, J=2.0 Hz, 1H), 8.45 (d, J=9.3 Hz, 1H), 8.23 (d, J=5.6 Hz, 1H), 7.97 (br s, 1H), 7.82 (d, J=7.9 Hz, 1H), 7.62-7.59 (m, 3H), 7.55-7.53 (m, 1H), 7.47-7.39 (m, 4H), 7.30-7.26 (m, 3H), 7.14 (m, 1H), 6.81 (d, J=15.6 Hz, 1H), 6.52 (dd, J=8.2, 2.5 Hz, 1H), 6.48 (d, J=5.3 Hz, 1H), 3.99 (t, J=6.0 Hz, 3H), 3.87 (s, 3H), 2.68-2.64 (m, 2H), 2.23 (s, 6H). ES-LC/MS m/z=626 [M+H]+. absorbed onto silica gel purified by silica gel chromatography