tert-butyl N-(3-azidopropyl)carbamate

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of compound 5 (12.56 g: 60 mmol) in dry DMF (150 mL) was added in small portions NaN3 (11.7 g: 180 mmol) with stirring over 30 min. The resulting solution was heated to 50° C. for 1 h and then stirred overnight at room temperature. Water (50 mL) was added with stirring, the solvent was removed, and the residue was extracted with ethyl acetate (2×175 mL). The combined organic layers were washed sequentially with water (2×50 mL) and brine (2×50 mL). The organic extract was dried over anhydrous sodium sulfate and evaporated to give compound 6 as a light yellow oil (10.54 g; 87% yield). 1H NMR (CDCl3-d6) δ 4.9 (s, 1H), 3.3 (m, 2H), 3.2 (m, 2H), 1.7 (m, 2H), 1.4 (s, 9H). stirred overnight at room temperature with stirring the solvent was removed the residue was extracted with ethyl acetate (2×175 mL) The combined organic layers were washed sequentially with water (2×50 mL) and brine (2×50 mL) The organic extract was dried over anhydrous sodium sulfate evaporated

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of compound 5 (12.56 g: 60 mmol) in dry DMF (150 mL) was added in small portions NaN3 (11.7 g: 180 mmol) with stirring over 30 min. The resulting solution was heated to 50° C. for 1 h and then stirred overnight at room temperature. Water (50 mL) was added with stirring, the solvent was removed, and the residue was extracted with ethyl acetate (2×175 mL). The combined organic layers were washed sequentially with water (2×50 mL) and brine (2×50 mL). The organic extract was dried over anhydrous sodium sulfate and evaporated to give compound 6 as a light yellow oil (10.54 g; 87% yield). 1H NMR (CDCl3-d6) δ 4.9 (s, 1H), 3.3 (m, 2H), 3.2 (m, 2H), 1.7 (m, 2H), 1.4 (s, 9H). stirred overnight at room temperature with stirring the solvent was removed the residue was extracted with ethyl acetate (2×175 mL) The combined organic layers were washed sequentially with water (2×50 mL) and brine (2×50 mL) The organic extract was dried over anhydrous sodium sulfate evaporated

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1,1-dimethylethyl (3-hydroxypropyl)carbamate (1.612 g, 9.2 mmol) in toluene (40 mL) cooled with an ice bath was added triethylamine (1.282 mL, 9.20 mmol) then methanesulfonyl chloride (0.717 mL, 9.20 mmol) and the resulting mixture was stirred for 15 min. Tetrabutylammonium bromide (0.297 g, 0.920 mmol) was then added followed by a solution of sodium azide (5 g, 77 mmol) in water (20 mL) and the resulting mixture was stirred at 60° C. for 7 h then cooled to room temperature and diluted with Et2O (150 mL). The two layers were separated and the organic phase was washed with water then brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by SP4 using a 25 G silica cartridge gave 1,1-dimethylethyl (3-azidopropyl)carbamate (1.27 g, 6.34 mmol, 68.9% yield) as a colourless oil. then cooled to room temperature The two layers were separated the organic phase was washed with water brine, dried over MgSO4 concentrated in vacuo Purification of the residue by SP4

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1,1-dimethylethyl (3-hydroxypropyl)carbamate (1.612 g, 9.2 mmol) in toluene (40 mL) cooled with an ice bath was added triethylamine (1.282 mL, 9.20 mmol) then methanesulfonyl chloride (0.717 mL, 9.20 mmol) and the resulting mixture was stirred for 15 min. Tetrabutylammonium bromide (0.297 g, 0.920 mmol) was then added followed by a solution of sodium azide (5 g, 77 mmol) in water (20 mL) and the resulting mixture was stirred at 60° C. for 7 h then cooled to room temperature and diluted with Et2O (150 mL). The two layers were separated and the organic phase was washed with water then brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by SP4 using a 25 G silica cartridge gave 1,1-dimethylethyl (3-azidopropyl)carbamate (1.27 g, 6.34 mmol, 68.9% yield) as a colourless oil. then cooled to room temperature The two layers were separated the organic phase was washed with water brine, dried over MgSO4 concentrated in vacuo Purification of the residue by SP4

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-methylethyl[(2S,4R)-1-acetyl-6-ethynyl-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation, see Intermediate 58) (250 mg, 0.795 mmol) in a mixture of N,N-dimethylformamide (DMF) (4.5 mL) and methanol (0.500 mL) were successively added 1,1-dimethylethyl (3-azidopropyl)carbamate (for a preparation, see Intermediate 74) (318 mg, 1.590 mmol) and copper(I) iodide (7.57 mg, 0.040 mmol). The resulting mixture was stirred at 100° C. under microwave irradiation for 2 h, and then cooled to room temperature and partitioned between EtOAc and brine. The two layers were separated and the aqueous phase was extracted with EtOAc (3×). The combined organic layers were washed with brine, dried over a Na2SO4 cartridge and concentrated in vacuo. Purification of the residue by SP4 column using a 10 G silica cartridge (gradient: 2 to 10% MeOH in DCM) gave 1-methylethyl((2S,4R)-1-acetyl-6-{1-[3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)propyl]-1H-1,2,3-triazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (514 mg, 0.999 mmol, 126%) as a viscous yellow oil which was used in the next step without further purification. for a preparation cooled to room temperature partitioned between EtOAc and brine The two layers were separated the aqueous phase was extracted with EtOAc (3×) The combined organic layers were washed with brine dried over a Na2SO4 cartridge concentrated in vacuo Purification of the residue by SP4 column

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-methylethyl[(2S,4R)-1-acetyl-6-ethynyl-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation, see Intermediate 58) (250 mg, 0.795 mmol) in a mixture of N,N-dimethylformamide (DMF) (4.5 mL) and methanol (0.500 mL) were successively added 1,1-dimethylethyl (3-azidopropyl)carbamate (for a preparation, see Intermediate 74) (318 mg, 1.590 mmol) and copper(I) iodide (7.57 mg, 0.040 mmol). The resulting mixture was stirred at 100° C. under microwave irradiation for 2 h, and then cooled to room temperature and partitioned between EtOAc and brine. The two layers were separated and the aqueous phase was extracted with EtOAc (3×). The combined organic layers were washed with brine, dried over a Na2SO4 cartridge and concentrated in vacuo. Purification of the residue by SP4 column using a 10 G silica cartridge (gradient: 2 to 10% MeOH in DCM) gave 1-methylethyl((2S,4R)-1-acetyl-6-{1-[3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)propyl]-1H-1,2,3-triazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (514 mg, 0.999 mmol, 126%) as a viscous yellow oil which was used in the next step without further purification. for a preparation cooled to room temperature partitioned between EtOAc and brine The two layers were separated the aqueous phase was extracted with EtOAc (3×) The combined organic layers were washed with brine dried over a Na2SO4 cartridge concentrated in vacuo Purification of the residue by SP4 column

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of compound 5 (12.56 g: 60 mmol) in dry DMF (150 mL) was added in small portions NaN3 (11.7 g: 180 mmol) with stirring over 30 min. The resulting solution was heated to 50° C. for 1 h and then stirred overnight at room temperature. Water (50 mL) was added with stirring, the solvent was removed, and the residue was extracted with ethyl acetate (2×175 mL). The combined organic layers were washed sequentially with water (2×50 mL) and brine (2×50 mL). The organic extract was dried over anhydrous sodium sulfate and evaporated to give compound 6 as a light yellow oil (10.54 g; 87% yield). 1H NMR (CDCl3-d6) δ 4.9 (s, 1H), 3.3 (m, 2H), 3.2 (m, 2H), 1.7 (m, 2H), 1.4 (s, 9H). stirred overnight at room temperature with stirring the solvent was removed the residue was extracted with ethyl acetate (2×175 mL) The combined organic layers were washed sequentially with water (2×50 mL) and brine (2×50 mL) The organic extract was dried over anhydrous sodium sulfate evaporated