1-(叠氮甲基)-4-甲氧基苯

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:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

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-chloro-4-ethynylpyrimidine (200 mg, 1.4 mmol) and 1-(azidomethyl)-4-methoxybenzene (0.5 M in t-butanol, 2.9 mL, 1.44 mmol) in 1:1 water tBuOH (7.2 mL) was added copper(II) sulfate pentahydrate (36 mg, 0.14 mmol) and sodium ascorbate (143 mg, 0.72 mmol) and the reaction was stirred at room temperature for 2 hrs. The reaction was then partitioned between water (50 mL) and EtOAc (50 mL). The layers were separated and the aqueous phase was extracted once with EtOAc (50 mL). The combined organic phases were washed with saturated aqueous sodium chloride (50 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. Purification on silica (30-50% ethyl acetate in hexanes) afforded 2-chloro-4-[1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl]pyrimidine (256 mg, 59%) as a white solid. The reaction was then partitioned between water (50 mL) and EtOAc (50 mL) The layers were separated the aqueous phase was extracted once with EtOAc (50 mL) The combined organic phases were washed with saturated aqueous sodium chloride (50 mL) dried over anhydrous MgSO4 filtered concentrated under reduced pressure Purification on silica (30-50% ethyl acetate in hexanes)

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

实验步骤: A mixture of 1-(chloromethyl)-4-methoxybenzene (20 g, 128 mmol) and sodium azide (12.5 g, 192 mmol) in acetonitrile (255 mL) was refluxed for 5 h under N2 atmosphere. The mixture was filtered and concentrated in vacuo. The residue was diluted with DCM, washed with H2O and brine, dried over Na2SO4 and concentrated in vacuo to afford crude 1-(azidomethyl)-4-methoxybenzene. The residue was used for the next reaction without further purification. was refluxed for 5 h under N2 atmosphere The mixture was filtered concentrated in vacuo The residue was diluted with DCM washed with H2O and brine dried over Na2SO4 concentrated in vacuo

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of diisopropylamine (6.6 ml, 47.1 mmole) in tetrahydrofuran (80 ml) at -78° C. under an argon atmosphere was added 2.5 N butyllithium (17.4 ml, 43.5 mmole), and the mixture was stirred for 30 minutes. To this reaction mixture were next added a solution of ethyl propionate (4.0 ml, 39.5 mmole) in tetrahydrofuran (20 ml) and a solution of 2-nitrobenzaldehyde (4.0 g, 26.5 mmole) in tetrahydrofuran (20 ml) in this sequence, and the resulting mixture was further stirred at -78° C. for 30 minutes. To the reaction mixture were added tetrahydrofuran (10 ml) followed by water, and the mixture was extracted with ethyl acetate. The organic layer was washed with dilute hydrochloric acid, a saturated aqueous sodium hydrogen carbonate solution and a saturated aqueous saline in this sequence. After the organic layer was dried over anhydrous magnesium sulfate, the solvent was removed under reduced pressure to give ethyl 4-hydroxy-4-(2-nitrophenyl)-2-butynoate as an oily product. After the ethyl 4-hydroxy-4-(2-nitrophenyl)-2-butynoate thus obtained was dissolved in toluene (80 ml), 4-methoxybenzylazide (13.0 g, 79.7 mmole) was added to the solution and stirred under heating at 100° C. for 3 hours. The reaction mixture was then cooled to room temperature. Precipitates were collected by filtration, washed with toluene and desiccated to give ethyl 5-[hydroxy-(2-nitrophenyl)methyl]-1-(4-methoxybenzyl)-1,2, 3-triazole-4-carboxylate (a-2: highly polar product (MP)) (2.55 g, 15.7%). Furthermore, the filtrate was concentrated and purified by silica gel column chromatography (toluene : ethyl acetate =1:1) to give a 3:1 mixture (6.09 g, 37.4%) of ethyl 4-(hydroxy-(2-nitrophenyl)methyl)-1-(4-methoxybenzyl)-1, 2,3-triazole-5-carboxylate (a-1: low polar product (LP)) and a compound a-2. The reaction mixture was then cooled to room temperature Precipitates were collected by filtration washed with toluene

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

实验步骤: A solution of freshly prepared 4-methoxybenzyl chloride (45.85 g) in dry dimethylformamide (150 ml) was treated with sodium azide (19.35 g). The stirred mixture was heated at between 100° and 110° C. for 20 hours, and was then cooled and poured into water (1200 ml). The resulting oil was extracted with diethyl ether (2×500 ml) and the combined ethereal extracts were washed with water (2×250 ml), dried over magnesium sulphate, and evaporated to give crude 4-methoxybenzyl azide (45.3 g). The stirred mixture was heated at between 100° and 110° C. for 20 hours was then cooled The resulting oil was extracted with diethyl ether (2×500 ml) the combined ethereal extracts were washed with water (2×250 ml) dried over magnesium sulphate evaporated

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

实验步骤: A mixture of crude 4-methoxybenzyl azide (45.3 g; prepared as described below) and ethyl cyanoformate (33 g) in xylene (300 ml) was heated at reflux for 48 hours. The mixture was evaporated at below 40° C. and under reduced pressure to leave a residue of ethyl 1-(4-methoxybenzyl)-1H-tetrazole-5-carboxylate (69.36 g), m.p. 52° C. was heated at reflux for 48 hours The mixture was evaporated at below 40° C. and under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:

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-chloro-4-ethynylpyrimidine (200 mg, 1.4 mmol) and 1-(azidomethyl)-4-methoxybenzene (0.5 M in t-butanol, 2.9 mL, 1.44 mmol) in 1:1 water tBuOH (7.2 mL) was added copper(II) sulfate pentahydrate (36 mg, 0.14 mmol) and sodium ascorbate (143 mg, 0.72 mmol) and the reaction was stirred at room temperature for 2 hrs. The reaction was then partitioned between water (50 mL) and EtOAc (50 mL). The layers were separated and the aqueous phase was extracted once with EtOAc (50 mL). The combined organic phases were washed with saturated aqueous sodium chloride (50 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. Purification on silica (30-50% ethyl acetate in hexanes) afforded 2-chloro-4-[1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl]pyrimidine (256 mg, 59%) as a white solid. The reaction was then partitioned between water (50 mL) and EtOAc (50 mL) The layers were separated the aqueous phase was extracted once with EtOAc (50 mL) The combined organic phases were washed with saturated aqueous sodium chloride (50 mL) dried over anhydrous MgSO4 filtered concentrated under reduced pressure Purification on silica (30-50% ethyl acetate in hexanes)

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

实验步骤: To a solution of p-methoxybenzyl chloride (4.26 mL, 31.4 mmol) in DMF (20 mL) was added sodium azide (2.04 g, 31.4 mmol). The reaction mixture was stirred at room temperature for 48 hours, diluted with H2O (200 mL), and then extracted with ether. The combined organic layers were washed w/H2O, dried over Na2SO4, filtered and conc. The clear oil obtained (4.9 g, 96%) was pure enough to use. 1H NMR (CDCl3, 400 MHz) 7.26-7.23 (m, 2H); 6.93-6.89 (m, H); 4.27 (s, 2H); 3.82 (s, 3H). extracted with ether The combined organic layers were washed w/H2O dried over Na2SO4 filtered conc. The clear oil obtained (4.9 g, 96%)