偶氮二甲酸二苄酯

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 3-(tetrahydro-pyran-4-yl)-propionaldehyde (8.59 g, 0.06 mol) and dibenzyl azodicarboxylate (12.8 g, 0.042 mol) in MeCN (250 mL) at 0° C. was added (R-proline) (0.48 g, 0.0042 mol). After stirring the mixture at 0° C. for 15 h, ethanol (100 mL) and NaBH4 (1.56 g, 0.042 mol) were added, and the mixture was stirred at 0° C. for 40 min. The reaction was quenched by slow addition of 10% aq citric acid (15 mL), and the whole solution was concentrated in vacuo. This residue was diluted with EtOAc (200 mL), washed with brine (50 mL), dried over Na2SO4, and concentrated in vacuo to give crude product which was purified by column chromatography to give (S)-dibenzyl 1-(1-hydroxy-3-(tetrahydro-2H-pyran-4-yl)propan-2-yl)hydrazine-1,2-dicarboxylate (16.52 g, 89%). 1H NMR (CD3OD) δ 1.0-1.5 (m, 8H), 2.9-3.3 (m, 2H), 3.4-3.6 (m, 2H), 3.7-3.9 (m, 2H), 4.4-4.7 (m, 2H), 5.1-5.4 (m, 4H), 7.2-7.4 (m, 10H). the mixture was stirred at 0° C. for 40 min The reaction was quenched by slow addition of 10% aq citric acid (15 mL) the whole solution was concentrated in vacuo This residue was diluted with EtOAc (200 mL) washed with brine (50 mL) dried over Na2SO4 concentrated in vacuo to give crude product which was purified by column chromatography

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 3-(tetrahydro-pyran-4-yl)-propionaldehyde (8.59 g, 0.06 mol) and dibenzyl azodicarboxylate (12.8 g, 0.042 mol) in MeCN (250 mL) at 0° C. was added (R-proline) (0.48 g, 0.0042 mol). After stirring the mixture at 0° C. for 15 h, ethanol (100 mL) and NaBH4 (1.56 g, 0.042 mol) were added, and the mixture was stirred at 0° C. for 40 min. The reaction was quenched by slow addition of 10% aq citric acid (15 mL), and the whole solution was concentrated in vacuo. This residue was diluted with EtOAc (200 mL), washed with brine (50 mL), dried over Na2SO4, and concentrated in vacuo to give crude product which was purified by column chromatography to give (S)-dibenzyl 1-(1-hydroxy-3-(tetrahydro-2H-pyran-4-yl)propan-2-yl)hydrazine-1,2-dicarboxylate (16.52 g, 89%). 1H NMR (CD3OD) δ 1.0-1.5 (m, 8H), 2.9-3.3 (m, 2H), 3.4-3.6 (m, 2H), 3.7-3.9 (m, 2H), 4.4-4.7 (m, 2H), 5.1-5.4 (m, 4H), 7.2-7.4 (m, 10H). the mixture was stirred at 0° C. for 40 min The reaction was quenched by slow addition of 10% aq citric acid (15 mL) the whole solution was concentrated in vacuo This residue was diluted with EtOAc (200 mL) washed with brine (50 mL) dried over Na2SO4 concentrated in vacuo to give crude product which was purified by column chromatography

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 3-Butyl-8-chloro-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (100 mg, 0.354 mmol) and 4-(3-phenyl-5-isoxazolyl)-1-butanol (77 mg, 0.355 mmol) were dissolved in dry THF (4 ml) under nitrogen. A solution of dibenzyl azodicarboxylate (94%, 224 mg, 0.708 mmol) in dry THF (2 ml) was added. The mixture was cooled to 0° C. and a solution of triphenylphosphine (185 mg, 0.708 mmol) in dry THF (1 ml) was added. The mixture was stirred for 20 min at 0° C. then at room temperature overnight. The mixture was degassed then stirred with morpholine (0.308 ml) and tetrakis(triphenylphosphine)palladium(0) (82 mg) for 4.5 h. A further 60 mg of tetrakis(triphenylphosphine)palladium(0) was added and stirring continued overnight. The reaction was worked up by partition between EtOAc and 2M HCl, the organic phase evaporated and purified by aminopropyl SPE (5 g) washing with THF-MeOH (1:1), MeOH and eluting with DCM-MeOH (1:1) containing 5% AcOH. Further purification by MDAP afforded the title compound (56 mg). at room temperature overnight The mixture was degassed then stirred with morpholine (0.308 ml) and tetrakis(triphenylphosphine)palladium(0) (82 mg) for 4.5 h A further 60 mg of tetrakis(triphenylphosphine)palladium(0) was added stirring continued overnight by partition between EtOAc and 2M HCl the organic phase evaporated purified by aminopropyl SPE (5 g) washing with THF-MeOH (1:1), MeOH eluting with DCM-MeOH (1:1) containing 5% AcOH Further purification by MDAP

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

实验步骤: 3-Pentyl-8-chloro-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (5 g, 16.86 mmol) and 3-(1H-pyrazol-4-yl)propan-1-ol (2.12 g, 16.8 mmol) were stirred in dry THF (150 ml) at 3° C. Dibenzyl azodicarboxylate (10.05 g, 33.7 mmol) was added followed by the dropwise addition of triphenylphosphine (8.83 g, 33.7 mmol) in dry THF (70 ml). The mixture was allowed to warm to it and stirred for 18 h. Water (1 ml) was added and the solvents evaporated. The residue was taken up in Et2O (200 ml) from which a white solid, mostly triphenylphosphine oxide, crystallised and was filtered off. The filtrate was concentrated and further by-products crystallised from ether-cyclohexane. The remaining filtrate was concentrated (19.2 g) and purified on a Biotage™ system (400 g) eluting with EtOAc-cyclohexane (2:1) to afford the title compound as a white solid (2.89 g). to warm to it the solvents evaporated crystallised was filtered off The filtrate was concentrated further by-products crystallised from ether-cyclohexane The remaining filtrate was concentrated (19.2 g) purified on a Biotage™ system (400 g) eluting with EtOAc-cyclohexane (2:1)

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

实验步骤: To a solution of ethyl 2,5-dioxopyrrolidine-3-carboxylate (3.92 g) in ethyl acetate (60 ml) was added dibenzyl azodicarboxylate (7.27 g), followed by potassium carbonate (317 mg) at room temperature. After this mixture was stirred at room temperature for 1 hour, the mixture was filtered through a Celite pad. The filtrate was concentrated and the resulting residue was purified by a flash column chromatography (hexane:ethyl acetate=2:1) to give the ethyl 3-[N,N′-bis(benzyloxycarbonyl)hydrazino]-2,5-dioxopyrrolidine-3-carboxylate (10.1 g, 94%) as amorphous. the mixture was filtered through a Celite pad The filtrate was concentrated the resulting residue was purified by a flash column chromatography (hexane:ethyl acetate=2:1)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 3-(tetrahydro-2H-pyran-3-yl)propanal (8.25 g, 0.058 mol) and dibenzyl azodicarboxylate (94%, 12.3 g, 0.041 mol) in MeCN (250 mL) at 0° C. was added (R-proline) (0.47 g, 0.0041 mol). After stirring the mixture at 0° C. for 15 hr. ethanol (100 mL) and NaBH4 (1.56 g, 0.041 mol) was added, and the mixture was stirred at 0° C. for 40 min. The reaction was quenched by slow addition of 10% aqueous citric acid (15 ml), and the whole solution was concentrated in vacuo. This residue was diluted with EtOAc (200 ml), washed with saturated brine (1×50 mL), dried over Na2SO4, and concentrated in vacuo to give the crude product, which was purified through column chromatography to give dibenzyl 1-((2S)-1-hydroxy-3-(tetrahydro-2H-pyran-3-yl)propan-2-yl)hydrazine-1,2-dicarboxylate (14.68 g, 81%). the mixture was stirred at 0° C. for 40 min The reaction was quenched by slow addition of 10% aqueous citric acid (15 ml) the whole solution was concentrated in vacuo This residue was diluted with EtOAc (200 ml) washed with saturated brine (1×50 mL) dried over Na2SO4 concentrated in vacuo to give the crude product, which was purified through column chromatography

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 3-(tetrahydro-2H-pyran-3-yl)propanal (8.25 g, 0.058 mol) and dibenzyl azodicarboxylate (94%, 12.3 g, 0.041 mol) in MeCN (250 mL) at 0° C. was added (R-proline) (0.47 g, 0.0041 mol). After stirring the mixture at 0° C. for 15 hr, ethanol (100 mL) and NaBH4 (1.56 g, 0.041 mol) was added, and the mixture was stirred at 0° C. for 40 min. The reaction was quenched by slow addition of 10% aqueous citric acid (15 ml), and the whole solution was concentrated in vacuo. This residue was diluted with EtOAc (200 ml), washed with saturated brine (1×50 mL), dried over Na2SO4, and concentrated in vacuo to give the crude product, which was purified through column chromatography to give dibenzyl 1-((2S)-1-hydroxy-3-(tetrahydro-2H-pyran-3-yl)propan-2-yl)hydrazine-1,2-dicarboxylate (14.68 g, 81%). the mixture was stirred at 0° C. for 40 min The reaction was quenched by slow addition of 10% aqueous citric acid (15 ml) the whole solution was concentrated in vacuo This residue was diluted with EtOAc (200 ml) washed with saturated brine (1×50 mL) dried over Na2SO4 concentrated in vacuo to give the crude product, which was purified through column chromatography

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 3-(tetrahydro-2H-pyran-3-yl)propanal (8.25 g, 0.058 mol) and dibenzyl azodicarboxylate (94%, 12.3 g, 0.041 mol) in MeCN (250 mL) at 0° C. was added (R-proline) (0.47 g, 0.0041 mol). After stirring the mixture at 0° C. for 15 hr, ethanol (100 mL) and NaBH4 (1.56 g, 0.041 mol) was added, and the mixture was stirred at 0° C. for 40 min. The reaction was quenched by slow addition of 10% aqueous citric acid (15 ml), and the whole solution was concentrated in vacuo. This residue was diluted with EtOAc (200 ml), washed with saturated brine (1×50 mL), dried over Na2SO4, and concentrated in vacuo to give the crude product, which was purified through column chromatography to give dibenzyl 1-((2S)-1-hydroxy-3-(tetrahydro-2H-pyran-3-yl)propan-2-yl)hydrazine-1,2-dicarboxylate (14.68 g, 81%). the mixture was stirred at 0° C. for 40 min The reaction was quenched by slow addition of 10% aqueous citric acid (15 ml) the whole solution was concentrated in vacuo This residue was diluted with EtOAc (200 ml) washed with saturated brine (1×50 mL) dried over Na2SO4 concentrated in vacuo to give the crude product, which was purified through column chromatography

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 3-(tetrahydro-pyran-4-yl)-propionaldehyde (8.59 g, 0.06 mol) and dibenzyl azodicarboxylate (12.8 g, 0.042 mol) in MeCN (250 mL) at 0° C. was added (R-proline) (0.48 g, 0.0042 mol). After stirring the mixture at 0° C. for 15 h, ethanol (100 mL) and NaBH4 (1.56 g, 0.042 mol) were added, and the mixture was stirred at 0° C. for 40 min. The reaction was quenched by slow addition of 10% aq citric acid (15 mL), and the whole solution was concentrated in vacuo. This residue was diluted with EtOAc (200 mL), washed with brine (50 mL), dried over Na2SO4, and concentrated in vacuo to give crude product which was purified by column chromatography to give (S)-dibenzyl 1-(1-hydroxy-3-(tetrahydro-2H-pyran-4-yl)propan-2-yl)hydrazine-1,2-dicarboxylate (16.52 g, 89%). 1H NMR (CD3OD) δ 1.0-1.5 (m, 8H), 2.9-3.3 (m, 2H), 3.4-3.6 (m, 2H), 3.7-3.9 (m, 2H), 4.4-4.7 (m, 2H), 5.1-5.4 (m, 4H), 7.2-7.4 (m, 10H). the mixture was stirred at 0° C. for 40 min The reaction was quenched by slow addition of 10% aq citric acid (15 mL) the whole solution was concentrated in vacuo This residue was diluted with EtOAc (200 mL) washed with brine (50 mL) dried over Na2SO4 concentrated in vacuo to give crude product which was purified by column chromatography

反应条件: temp:0.00; pressure:0.00; stir: