azidobenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a capped vial (1 mL) containing a solution of phenylazide (6.6 mg, 55 μmol) in dry THF (300 μL), was added [RhCl(cod)]2 (0.27 mg, 0.55 μmol), and 1,2-bis(diphenylphosphino)ethane (0.66 mg, 1.65 μmol), and was shaken until the solution was homogeneous. After addition of a solution of methyl magnesium bromide (18.5 μL of 3M solution in ether, 55 μmol), the resulting mixture was transferred to the micro-autoclave, which was pre-charged with [11C]CO. The micro-autoclave was heated at 120° C. for 5 min under 35 MPa and the crude product was transferred to a reduced pressure vial. The radioactivity was measured before and after the vial was flushed with N2 (the [11C]CO-trapping efficiency of 96% was determined based on these values). The solution was dissolved in ammonium formate (0.5 mL, pH=3.5) and heated at 120° C. for 1 min. A small amount of crude product was collected and analyzed by the reversed phase HPLC. Yield of product: 91%. The product was identified by HPLC with an added authentic reference compound. was pre-charged with [11C]CO was flushed with N2 (the [11C]CO- The solution was dissolved in ammonium formate (0.5 mL, pH=3.5) heated at 120° C. for 1 min A small amount of crude product was collected

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a capped vial (1 mL) containing a solution of phenylazide (6.6 mg, 55 μmol) in dry THF (300 μL), was added [RhCl(cod)]2 (0.27 mg, 0.55 μmol), and 1,2-bis(diphenylphosphino)ethane (0.44 mg, 1.1 μmol) and was shaken until the solution was homogeneous. After addition of aniline (10 μL, 110 μmol), the resulting mixture was transferred to the micro-autoclave, which was pre-charged with [11C]CO. The autoclave (250 μL) was heated at 120° C. for 5 min under 35 MPa and the crude product was transferred to a reduced pressure vial. The radioactivity was measured before and after the vial was flushed with N2 (the [11C]CO-trapping efficiency of 82% was determined based on these values). A small amount of crude product was collected and analyzed by the reversed phase HPLC. Yield of product: 82%. The product was identified by HPLC with an added authentic reference compound. was pre-charged with [11C]CO was flushed with N2 (the [11C]CO- A small amount of crude product was collected

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: n-Butyllithium (1.6 M, 7.5 ml, 12 mmol) was added dropwise at −78° C. over 5 min to a stirred solution of methyl 2-cyanomethylbenzoate (Tetrahedron Lett., 1991, 32, 4133-4134) (2.10 g, 12 mmol) in dry THF (50 ml) under nitrogen. The deep red solution was stirred at −78° C. for 10 min, followed by the addition of a solution of phenyl azide (1.47 g, 12.3 mmol) in dry THF (10 ml). The green solution was stirred at −78° C. for 1.5 h then warmed to r.t. over 30 min, becoming bright blue. Saturated aqueous ammonium chloride (50 ml) was added and the mixture was acidified to pH 5 with 1M citric acid. The white precipitate was collected and washed with water and diethyl ether, then dried to give 3-phenyl-1,2,3-triazolo[4,5-c]isoquinolin-5-one (2.00 g, 64%). δH (360 MHz; DMSO) 7.58-7.68 (4H, m), 7.80-7.84 (2H, m), 7.93 (1H, ddd, J=8, 8 and 1), 8.30 (2H, d, J=8) and 12.80 (1H, s); m/z (ES+) 263 (M+H+). The green solution was stirred at −78° C. for 1.5 h then warmed to r.t. over 30 min The white precipitate was collected washed with water and diethyl ether dried

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: n-Butyllithium (1.6 M, 7.5 ml, 12 mmol) was added dropwise at −78° C. over 5 min to a stirred solution of methyl 2-cyanomethylbenzoate (Tetrahedron Lett., 1991, 32, 4133-4134) (2.10 g, 12 mmol) in dry THF (50 ml) under nitrogen. The deep red solution was stirred at −78° C. for 10 min, followed by the addition of a solution of phenyl azide (1.47 g, 12.3 mmol) in dry THF (10 ml). The green solution was stirred at −78° C. for 1.5 h then warmed to r.t. over 30 min, becoming bright blue. Saturated aqueous ammonium chloride (50 ml) was added and the mixture was acidified to pH 5 with 1M citric acid. The white precipitate was collected and washed with water and diethyl ether, then dried to give 3-phenyl-1,2,3-triazolo[4,5-c]isoquinolin-5-one (2.00 g, 64%). δH (360 MHz; DMSO) 7.58-7.68 (4H, m), 7.80-7.84 (2H, m), 7.93 (1H, ddd, J=8, 8 and 1), 8.30 (2H, d, J=8) and 12.80 (1H, s); m/z (ES+) 263 (M+H+). The green solution was stirred at −78° C. for 1.5 h then warmed to r.t. over 30 min The white precipitate was collected washed with water and diethyl ether dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In the method of preparation, the reaction between the N-vinylpyrrolidinone and the phenyl azide is carried out at room temperature in ethanol as solvent, and allowed to stand in the dark for several weeks, depending on the reactivity of the phenyl azides. Refluxing the reaction mixture eliminates the 5-(2-oxo-1-pyrrolidino) group and yields the 1-phenyl triazole. In the method of preparation to stand in the dark for several weeks Refluxing the reaction mixture

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (3S,4S)-tert-butyl 3-((3-carbamoyl-6-ethynylpyrrolo[1,2-b]pyridazin-4-yl)amino)-4-ethylpyrrolidine-1-carboxylate from Step 2 of Example 292 (71 mg, 0.179 mmol) in toluene (2 mL) and DMF (0.2 mL) was added azidobenzene (149 mg, 1.250 mmol). The flask was purged with nitrogen, and the reaction solution was stirred at room temperature for 1 hour, then warmed to 95° C. After stirring over two nights, the reaction was cooled to room temperature. The volatiles were removed in vacuo and the residue was diluted with 3 mL DMF and purified by via preparative HPLC with the following conditions: Column: Phenomenex Luna C18, 21.5×250 mm, 5-μm particles; Mobile Phase A: 10:90 methanol:water with 0.1% trifluoroacetic acid; Mobile Phase B: 90:10 methanol:water with 0.1% trifluoroacetic acid; Gradient: 30-100% B over 14 minutes, then a 2-minute hold at 100% B; Flow: 25 mL/min. Fractions containing the desired product were combined and concentrated via centrifugal evaporation to remove the methanol. The solution was neutralized with 1N NaOH, and was then partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer was dried over sodium sulfate. Filtration and evaporation afforded the title compound (41 mg, 42% yield). MS (ES+) m/z: 517.1 (M+H); LC retention time: 3.385 min (analytical LCMS Method J). The flask was purged with nitrogen warmed to 95° C After stirring over two nights the reaction was cooled to room temperature The volatiles were removed in vacuo the residue was diluted with 3 mL DMF purified by via preparative HPLC with the following conditions Gradient: 30-100% B over 14 minutes a 2-minute hold Fractions containing the desired product concentrated via centrifugal evaporation to remove the methanol was then partitioned between ethyl acetate and saturated aqueous sodium bicarbonate The organic layer was dried over sodium sulfate Filtration and evaporation

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of the crude phenylazide (1.37 g, 11.5 mmol) from above and 1-tert-butoxycarbonyl-4-ethynyl-1,2,3,6-tetrahydropyridine (2 g, 9.6 mmol) (Example 1) in toluene (20 ml) was refluxed for 24 hours. The reaction was cooled and the solvent evaporated in vacuo. The crude residue was chromatographed on silica eluting with ethyl acetate/petrol (60°-80° C.) (1:2) to give the 1-tert-butoxycarbonyl-4-(1-phenyl-1,2,3-triazol-4-yl)-1,2,3,6-tetrahydropyridine as a tan waxy solid (853 mg, 27%), δH (CDCl3) 1.49 (9H, s, OC(CH3)3), 2.59 (2H, br s, tetrahydropyridinyl CH2), 3.67 (2H, t, J 5.2 Hz, tetrahydropyridinyl CH2), 4.12 (2H, br s, tetrahydropyridinyl CH2), 6.53 (1H, br s, tetrahydropyridinyl 5-H), 7.42-7.46 (1H, m, ArH), 7.51-7.55 (2H, m, ArH), 7.72-7.75 (2H, m, ArH), 7.87 (1H, s, triazolyl 5-H). was refluxed for 24 hours The reaction was cooled the solvent evaporated in vacuo The crude residue was chromatographed on silica eluting with ethyl acetate/petrol (60°-80° C.) (1:2)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of the crude phenylazide (1.37 g, 11.5 mmol) from above and 1-tert-butoxycarbonyl-4-ethynyl-1,2,3,6-tetrahydropyridine (2 g, 9.6 mmol) (Example 1) in toluene (20 ml) was refluxed for 24 hours. The reaction was cooled and the solvent evaporated in vacuo. The crude residue was chromatographed on silica eluting with ethyl acetate/petrol (60°-80° C.) (1:2) to give the 1-tert-butoxycarbonyl-4-(1-phenyl-1,2,3-triazol-4-yl)-1,2,3,6-tetrahydropyridine as a tan waxy solid (853 mg, 27%), δH (CDCl3) 1.49 (9H, s, OC(CH3)3), 2.59 (2H, br s, tetrahydropyridinyl CH2), 3.67 (2H, t, J 5.2 Hz, tetrahydropyridinyl CH2), 4.12 (2H, br s, tetrahydropyridinyl CH2), 6.53 (1H, br s, tetrahydropyridinyl 5-H), 7.42-7.46 (1H, m, ArH), 7.51-7.55 (2H, m, ArH), 7.72-7.75 (2H, m, ArH), 7.87 (1H, s, triazolyl 5-H). was refluxed for 24 hours The reaction was cooled the solvent evaporated in vacuo The crude residue was chromatographed on silica eluting with ethyl acetate/petrol (60°-80° C.) (1:2)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phenylhydrazine (6.7 g, 62 mmol) was added dropwise to a cold (0° C.) solution of concentrated hydrochloric acid (60 ml) over a period of 10 minutes. Diethyl ether (20 ml) was then added, followed by the dropwise addition of a solution of sodium nitrite (5 g, 72 mmol) in water (6 ml), keeping the temperature below 5° C. The reaction was then stirred at 0° C. for 1 hour and then extracted with ethyl acetate (3×100 ml). The combined organic layers were washed with water (2×50 ml), saturated brine (50 ml), dried (MgSO4) and carefully evaporated in vacuo to give the crude title compound as a red oil (3.3 g, 45%). the temperature below 5° C extracted with ethyl acetate (3×100 ml) The combined organic layers were washed with water (2×50 ml), saturated brine (50 ml) dried (MgSO4) carefully evaporated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of trimethyl(thiophen-2-ylethynyl)silane (50 mg, 0.2777 mmol), phenyl azide (0.5 M solution, 1.1 ml, 0.555 mmol), and CuI (52.87 mg, 0.2777 mmol) in THF (1 ml) was added 1,1,4,7,7-pentamethyldiethlenetriamine (0.116 ml, 0.555 mmol) and 1M TBAF.3H2O (0.554 ml, 0.554 mmol). After stirring the reaction mixture for 20 hours at room temperature, it was quenched with saturated ammonium chloride solution and was extracted with ethyl acetate. The combined organic layers were washed with water, dried over anhydrous sodium sulfate and evaporated. The crude material was purified by column chromatography (100-200 mesh silica gel) using 5% ethyl acetate in hexane as eluant to yield 1-phenyl-4-(thiophen-2-yl)-1H-1,2,3-triazole (30 mg, 0.132 mol, yield 47.61%) with an HPLC purity of 97.64%. LC-MS [M+H] 228.2 (C12H9N3S+H, expected 228.05). The 1H-NMR spectra was in accordance with the chemical structure. it was quenched with saturated ammonium chloride solution was extracted with ethyl acetate The combined organic layers were washed with water dried over anhydrous sodium sulfate evaporated The crude material was purified by column chromatography (100-200 mesh silica gel)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of furan-2-ylethynyl)trimethylsilane (100 mg, 0.6097 mmol), phenyl azide (0.5 M solution, 2.42 ml, 1.2195 mmol), and CuI (116.11 mg, 0.6097 mmol) in THF (2 ml) was added 1,1,4,7,7-pentamethyldiethlene triamine (0.254 ml, 1.2195 mmol) and 1M TBAF.3H2O (1.20 ml, 1.2195 mmol). After stirring the reaction mixture for 20 hours at room temperature, it was quenched with saturated ammonium chloride solution and was extracted with ethyl acetate. The combined organic layers were washed with water, dried over anhydrous sodium sulfate and evaporated. The crude material was purified by column chromatography (100-200 mesh silica gel) using 5% ethyl acetate in hexane as eluent to yield 4-(furan-2-yl)-1-phenyl-1H-1,2,3-triazole (80 mg, 0.378 mmol, yield 62.18%) with an HPLC purity of 98.82%. LC-MS [M+H] 212 (C12H9N3O+H expected 212.07), mp 118-120° C. The 1H-NMR spectra was in accordance with the chemical structure. it was quenched with saturated ammonium chloride solution was extracted with ethyl acetate The combined organic layers were washed with water dried over anhydrous sodium sulfate evaporated The crude material was purified by column chromatography (100-200 mesh silica gel)