2-azidoethyl methanesulfonate

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of bromoethanol (7.5 g, 60.0 mmol) and sodium azide (5.0 g, 76.9 mmol) in HMPT (30 ml) was heated at 115° C. for 2.5 h. The reaction mixture was cooled to 23° C. and diluted with CH2Cl2 (100 ml). The solids were removed by filtration and the CH2Cl2 was evaporated on the rotary evaporator leaving a yellow liquid which was cooled to 0° C. and successively treated with mesylchloride (5.57 ml, 72.0 mmol) and triethylamine (10.0 ml, 72.0 mmol). The reaction mixture was stirred at 0° C. for 1 h, then at 23° C. for 6 h, and poured into H2O (300 ml). The aqueous solution was extracted with ether (1×200 ml, 4×100 ml); the ether extracts were combined, washed with 1N HCl solution, H2O saturated NaHCO3 solution and H2O, dried over anhydrous MgSO4 and concentrated on a rotary evaporator to an orange liquid which was distilled under high vacuum bp 95°-100° C. 0.3 torr, 5.8 g, 58.5%; ir (neat) νmax : 2005 (s, N3), 1345 (s, SO2 --O), 1175 (m, SO2 --O) cm-1. 1Hmr (CDCl3) δ: 3.03 (s, 3H, OCH3), 3.43-3.76 (m, 2H, H-2) and 4.2-4.46 ppm (m, 2H, H-1). The solids were removed by filtration the CH2Cl2 was evaporated on the rotary evaporator leaving a yellow liquid which was cooled to 0° C. at 23° C. for 6 h The aqueous solution was extracted with ether (1×200 ml, 4×100 ml) washed with 1N HCl solution, H2O saturated NaHCO3 solution and H2O dried over anhydrous MgSO4 concentrated on a rotary evaporator to an orange liquid which was distilled under high vacuum bp 95°-100° C

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

Procedure: 7-Nitro-1,2,4,5-tetrahydro-3H-3-benzazepine (1.1 g), 2-methanesulphonyloxyethyl azide (0.92 g) and potassium carbonate (0.76 g) were heated under reflux in acetonitrile for 18 hours. The solvent was evaporated in vacuo and the residue taken up in ethyl acetate then washed three times with aqueous sodium carbonate and three times with brine. The organic layer was dried, filtered and evaporated in vacuo to give an oil which was purified by chromatography on silica eluting with ethyl acetate/hexane (1:1). The product-containing fractions were combined and evaporated to give the title compound as an oil, yield 0.65 g, which was used without further purification. The solvent was evaporated in vacuo then washed three times with aqueous sodium carbonate and three times with brine The organic layer was dried filtered evaporated in vacuo to give an oil which was purified by chromatography on silica eluting with ethyl acetate/hexane (1:1) evaporated

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

Procedure: A solution of methanesulphonyl chloride (5.7 g) in methylene chloride (20 ml) was added dropwise to a stirred solution of 2-azidoethanol (4.3 g) and triethylamine (5.0 g) in methylene chloride (80 ml). After 2 hours stirring at room temperature the reaction mixture was washed with water, dried (MgSO4) and evaporated to dryness in vacuo to give the title compound as a yellow oil, yield 7 g, which was used directly without further purification. was washed with water dried (MgSO4) evaporated to dryness in vacuo

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of bromoethanol (7.5 g, 60.0 mmol) and sodium azide (5.0 g, 76.9 mmol) in HMPT (30 ml) was heated at 115° C. for 2.5 h. The reaction mixture was cooled to 23° C. and diluted with CH2Cl2 (100 ml). The solids were removed by filtration and the CH2Cl2 was evaporated on the rotary evaporator leaving a yellow liquid which was cooled to 0° C. and successively treated with mesylchloride (5.57 ml, 72.0 mmol) and triethylamine (10.0 ml, 72.0 mmol). The reaction mixture was stirred at 0° C. for 1 h, then at 23° C. for 6 h, and poured into H2O (300 ml). The aqueous solution was extracted with ether (1×200 ml, 4×100 ml); the ether extracts were combined, washed with 1 N HCl solution, H2O saturated NaHCO3 solution and H2O, dried over anhydrous MgSO4 and concentrated on a rotary evaporator to an orange liquid which was distilled under high vacuum bp 95°-100° C. 0.3 torr, 5.8 g, 58.5%; ir (neat) νmax : 2005 (s, N3), 1345 (s, SO2 --O), 1175 (m, SO2 --O) cm-1. 1Hmr (CDCl3) δ: 3.03 (s, 3H, OCH3), 3.43-3.76 (m, 2H, H-2) and 4.2-4.46 ppm (m, 2H, H-1). The solids were removed by filtration the CH2Cl2 was evaporated on the rotary evaporator leaving a yellow liquid which was cooled to 0° C. at 23° C. for 6 h The aqueous solution was extracted with ether (1×200 ml, 4×100 ml) washed with 1 N HCl solution, H2O saturated NaHCO3 solution and H2O dried over anhydrous MgSO4 concentrated on a rotary evaporator to an orange liquid which was distilled under high vacuum bp 95°-100° C

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of bromoethanol (7.5 g, 60.0 mmol) and sodium azide (5.0 g, 76.9 mmol) in HMPT (30 ml) was heated at 115° C. for 2.5 h. The reaction mixture was cooled to 23° C. and diluted with CH2Cl2 (100 ml). The solids were removed by filtration and the CH2Cl2 was evaporated on the rotary evaporator leaving a yellow liquid which was cooled to 0° C. and successively treated with mesylchloride (5.57 ml, 72.0 mmol) and triethylamine (10.0 ml, 72.0 mmol). The reaction mixture was stirred at 0° C. for 1 h, then at 23° C. for 6 h, and poured into H2O (300 ml). The aqueous solution was extracted with ether (1×200 ml, 4×100 ml); the ether extracts were combined, washed with 1 N HCl solution, H2O saturated NaHCO3 solution and H2O, dried over anhydrous MgSO4 and concentrated on a rotary evaporator to an orange liquid which was distilled under high vacuum bp 95°-100° C. 0.3 torr, 5.8 g, 58.5%; ir (neat) νmax : 2005 (s, N3), 1345 (s, SO2 --O), 1175 (m, SO2 --O) cm-1. 1Hmr (CDCl3) δ: 3.03 (s, 3H, OCH3), 3.43-3.76 (m, 2H, H-2) and 4.2-4.46 ppm (m, 2H, H-1). The solids were removed by filtration the CH2Cl2 was evaporated on the rotary evaporator leaving a yellow liquid which was cooled to 0° C. at 23° C. for 6 h The aqueous solution was extracted with ether (1×200 ml, 4×100 ml) washed with 1 N HCl solution, H2O saturated NaHCO3 solution and H2O dried over anhydrous MgSO4 concentrated on a rotary evaporator to an orange liquid which was distilled under high vacuum bp 95°-100° C

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

Procedure: Di-tert-butyl (4S)—N-(tert-butoxycarbonyl)-4-prop-2-yn-1-yl-L-glutamate (60 mg, 151 μmol) and 2-azidoethyl methanesulfonate (37.4 mg, 226 μmol) were dissolved in tetrahydrofuran (4 ml). To the solution, copper(I) iodide (2.9 mg, 15 μmol) and N,N-diisopropylethylamine (32 μl, 181 μmol) were added and the mixture was stirred for 18 h at room temperature. The mixture was then concentrated in vacuo and the residue was purified by preparative reversed phase HPLC. The product fractions were collected, lyophilized, and purified again by silicagel chromatography to yield 50 mg (47%) of the product. The mixture was then concentrated in vacuo the residue was purified by preparative reversed phase HPLC The product fractions were collected purified again by silicagel chromatography

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

Procedure: 3-methoxypyridine-2-one (0.40 g, 3.20 mmol), 156a (0.79 g, 4.80 mmol), and K2CO3 (1.32 g, 9.60 mmol) stirred overnight in THF at reflux temperature. Reaction mixture was cooled down to room temperature. Reaction mixture was partitioned between CH2Cl2 (60 mL) and water (50 mL). Organic layer washed with water (2×35 mL), brine (1×30 mL). Organic layer dried on Na2SO4 and evaporated in vacuo. Crude product was purified by flash chromatography with stepwise gradient of CH2Cl2 and acetone (max 15%) to give 0.34 mg of 157a (55%) as colorless oil. 1H NMR (400 MHz, CDCl3) δ 6.77 (dd, J=6.9, 1.6 Hz, 1H), 6.48 (dd, J=7.5, 1.6 Hz, 1H), 5.96 (m, 1H), 3.91 (m, 2H), 3.62 (s, 3H), 3.52 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 157.39, 149.41, 128.61, 112.16, 104.37, 55.36, 49.00, 48.91. HRMS (EI) calcd for C8H10N4O2 [M]+ 194.0804. found 194.0816. at reflux temperature Reaction mixture Reaction mixture was partitioned between CH2Cl2 (60 mL) and water (50 mL) Organic layer washed with water (2×35 mL), brine (1×30 mL) Organic layer dried on Na2SO4 evaporated in vacuo Crude product was purified by flash chromatography with stepwise gradient of CH2Cl2 and acetone (max 15%)

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

Procedure: 3-methoxypyridine-2-one (0.40 g, 3.20 mmol), 156a (0.79 g, 4.80 mmol), and K2CO3 (1.32 g, 9.60 mmol) stirred overnight in THF at reflux temperature. Reaction mixture was cooled down to room temperature. Reaction mixture was partitioned between CH2Cl2 (60 mL) and water (50 mL). Organic layer washed with water (2×35 mL), brine (1×30 mL). Organic layer dried on Na2SO4 and evaporated in vacuo. Crude product was purified by flash chromatography with stepwise gradient of CH2Cl2 and acetone (max 15%) to give 0.34 mg of 157a (55%) as colorless oil. 1H NMR (400 MHz, CDCl3) δ 6.77 (dd, J=6.9, 1.6 Hz, 1H), 6.48 (dd, J=7.5, 1.6 Hz, 1H), 5.96 (m, 1H), 3.91 (m, 2H), 3.62 (s, 3H), 3.52 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 157.39, 149.41, 128.61, 112.16, 104.37, 55.36, 49.00, 48.91. HRMS (EI) calcd for C8H10N4O2 [M]+ 194.0804. found 194.0816. at reflux temperature Reaction mixture Reaction mixture was partitioned between CH2Cl2 (60 mL) and water (50 mL) Organic layer washed with water (2×35 mL), brine (1×30 mL) Organic layer dried on Na2SO4 evaporated in vacuo Crude product was purified by flash chromatography with stepwise gradient of CH2Cl2 and acetone (max 15%)

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

Procedure: Reaction of 6-azidohexanol (0.74 g, 5.22 mmol) and mesyl chloride (0.61 mL, 7.83 mmol) within 3 h as described for synthesis of 156a gave compound 156e (0.87 g) as a crude colorless oil.

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

Procedure: Reaction of 5-azidopentanol (1.1 g, 8.53 mmol) and mesyl chloride (0.98 mL, 12.79 mmol) within 3 h as described for synthesis of 156a gave compound 156d (1.54 g) as a crude colorless oil.

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

Procedure: Reaction of 5-azidopentanol (1.1 g, 8.53 mmol) and mesyl chloride (0.98 mL, 12.79 mmol) within 3 h as described for synthesis of 156a gave compound 156d (1.54 g) as a crude colorless oil.

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

Procedure: Reaction of 4-azidobutanol (0.80 g, 6.95 mmol) and mesyl chloride (1.48 mL, 10.43 mmol) within 3 h as described for synthesis of 156a gave compound 156c (1.33 g) as a crude colorless oil.