1-azido-4-iodobenzene

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

Procedure: 4-Iodoaniline (32, 6.00 g, 27.4 mmol) was dissolved in 25 mL TFA and stirred in ice bath. Solid NaNO2 (2.07 g, 30.1 mmol) was added in small portions. The resulting mixture was stirred for 30 min in the ice bath. Sodium azide (1.87 g, 28.8 mmol) was dissolved in 10 mL water and chilled in ice bath. This cold solution was then added to the TFA solution in three portions. The mixture was stirred in ice bath for 1 hr and concentrated in vacuo to remove TFA. The residue was taken into 600 mL DCM and washed with water three times. The organic phase was dried using MgSO4 and concentrated in vacuo to afford 1-azido-4-iodobenzene 33 as a brownish waxy solid in >99% yield. In the mean time, 5-chlorothiophene-2-carboxylic acid (4, 9.13 g, 56 mmol) was dissolved in 200 mL dry DCM along with 0.5 mL dry DMF. To the vigorously stirred solution was carefully added oxalyl chloride (14.7 mL, 169 mmol) dropwise. The resulting solution was stirred for 3 hrs at RT and concentrated in vacuo. The residue was pumped to dryness and then dissolved in 300 mL dry DCM. To this solution was added propargylamine (5.8 mL, 84 mmol) dropwise. The mixture was stirred at RT for overnight and a lot of solid precipitated out. To this mixture was added 600 mL hexane. The mixture was vigorously stirred for a few hours and filtered for the solid (product 34). The solid (9.47 g, 85%) was washed with hexane and was pure enough for direct use without further purification. MS found for C8H6ClNOS as (M+H)+ 200.0, 202.0. chilled in ice bath The mixture was stirred in ice bath for 1 hr concentrated in vacuo to remove TFA washed with water three times The organic phase was dried concentrated in vacuo

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

Procedure: 6 g of p-iodoaniline was dispersed in a solution comprising 25 cc of water and 7.5 cc of 36% hydrochloric acid and cooled with ice. 2.1 g of sodium nitrite was dissolved in 13 ml of water and the resulting solution was added dropwise slowly to the dispersion to effect the diazotization reaction. A solution of 2.5 g of sodium azide in 18 ml of water was added dropwise thereto and, after stirring for one hour, the mixture was subjected to extraction with benzene. After the dehydration with sodium sulfate, benzene was evaporated to obtain p-azidoiodobenzene. cooled with ice the resulting solution was added dropwise slowly to the dispersion the diazotization reaction the mixture was subjected to extraction with benzene After the dehydration with sodium sulfate, benzene was evaporated

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

Procedure: 4-Iodoaniline (32, 6.00 g, 27.4 mmol) was dissolved in 25 mL TFA and stirred in ice bath. Solid NaNO2 (2.07 g, 30.1 mmol) was added in small portions. The resulting mixture was stirred for 30 min in the ice bath. Sodium azide (1.87 g, 28.8 mmol) was dissolved in 10 mL water and chilled in ice bath. This cold solution was then added to the TFA solution in three portions. The mixture was stirred in ice bath for 1 hr and concentrated in vacuo to remove TFA. The residue was taken into 600 mL DCM and washed with water three times. The organic phase was dried using MgSO4 and concentrated in vacuo to afford 1-azido-4-iodobenzene 33 as a brownish waxy solid in >99% yield. In the mean time, 5-chlorothiophene-2-carboxylic acid (4, 9.13 g, 56 mmol) was dissolved in 200 mL dry DCM along with 0.5 mL dry DMF. To the vigorously stirred solution was carefully added oxalyl chloride (14.7 mL, 169 mmol) dropwise. The resulting solution was stirred for 3 hrs at RT and concentrated in vacuo. The residue was pumped to dryness and then dissolved in 300 mL dry DCM. To this solution was added propargylamine (5.8 mL, 84 mmol) dropwise. The mixture was stirred at RT for overnight and a lot of solid precipitated out. To this mixture was added 600 mL hexane. The mixture was vigorously stirred for a few hours and filtered for the solid (product 34). The solid (9.47 g, 85%) was washed with hexane and was pure enough for direct use without further purification. MS found for C8H6ClNOS as (M+H)+ 200.0, 202.0. chilled in ice bath The mixture was stirred in ice bath for 1 hr concentrated in vacuo to remove TFA washed with water three times The organic phase was dried concentrated in vacuo

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

Procedure: 6 g of p-iodoaniline was dispersed in a solution comprising 25 cc of water and 7.5 cc of 36% hydrochloric acid and cooled with ice. 2.1 g of sodium nitrite was dissolved in 13 ml of water and the resulting solution was added dropwise slowly to the dispersion to effect the diazotization reaction. A solution of 2.5 g of sodium azide in 18 ml of water was added dropwise thereto and, after stirring for one hour, the mixture was subjected to extraction with benzene. After the dehydration with sodium sulfate, benzene was evaporated to obtain p-azidoiodobenzene. cooled with ice the resulting solution was added dropwise slowly to the dispersion the diazotization reaction the mixture was subjected to extraction with benzene After the dehydration with sodium sulfate, benzene was evaporated

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

Procedure: To a solution of 4-iodobenzenamine (2.38 g, 10.9 mmol) in MeCN (20 mL) at 0° C. was added tert-butyl nitrite (1.95 mL, 1.69 g, 16.4 mmol) and azidotrimethylsilane (1.70 mL, 1.49 g, 12.9 mmol). The reaction mixture was warmed to room temperature and stirred for 6 h, heated to 40° C. for 18 h, and diluted with EtOAc. The aqueous phase was washed with water (2×), brine (1×), dried over MgSO4, filtered, and concentrated to give 1-azido-4-iodobenzene which was used in the next step without further purification. heated to 40° C. for 18 h The aqueous phase was washed with water (2×), brine (1×) dried over MgSO4 filtered concentrated

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

Procedure: 4-Iodoaniline (32, 6.00 g, 27.4 mmol) was dissolved in 25 mL TFA and stirred in ice bath. Solid NaNO2 (2.07 g, 30.1 mmol) was added in small portions. The resulting mixture was stirred for 30 min in the ice bath. Sodium azide (1.87 g, 28.8 mmol) was dissolved in 10 mL water and chilled in ice bath. This cold solution was then added to the TFA solution in three portions. The mixture was stirred in ice bath for 1 hr and concentrated in vacuo to remove TFA. The residue was taken into 600 mL DCM and washed with water three times. The organic phase was dried using MgSO4 and concentrated in vacuo to afford 1-azido-4-iodobenzene 33 as a brownish waxy solid in >99% yield. In the mean time, 5-chlorothiophene-2-carboxylic acid (4, 9.13 g, 56 mmol) was dissolved in 200 mL dry DCM along with 0.5 mL dry DMF. To the vigorously stirred solution was carefully added oxalyl chlororide (14.7 mL, 169 mmol) dropwise. The resulting solution was stirred for 3 hrs at RT and concentrated in vacuo. The residue was pumped to dryness and then dissolved in 300 mL dry DCM. To this solution was added propargylamine (5.8 mL, 84 mmol) dropwise. The mixture was stirred at RT for overnight and a lot of solid precipitated out. To this mixture was added 600 mL hexane. The mixture was vigorously stirred for a few hours and filtered for the solid (product 34). The solid (9.47 g, 85%) was washed with hexane and was pure enough for direct use without further purification. MS found for C8H6ClNOS as (M+H)+ 200.0, 202.0. chilled in ice bath The mixture was stirred in ice bath for 1 hr concentrated in vacuo to remove TFA washed with water three times The organic phase was dried concentrated in vacuo

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

Procedure: 4-Iodoaniline (32, 6.00 g, 27.4 mmol) was dissolved in 25 mL TFA and stirred in ice bath. Solid NaNO2 (2.07 g, 30.1 mmol) was added in small portions. The resulting mixture was stirred for 30 min in the ice bath. Sodium azide (1.87 g, 28.8 mmol) was dissolved in 10 mL water and chilled in ice bath. This cold solution was then added to the TFA solution in three portions. The mixture was stirred in ice bath for 1 hr and concentrated in vacuo to remove TFA. The residue was taken into 600 mL DCM and washed with water three times. The organic phase was dried using MgSO4 and concentrated in vacuo to afford 1-azido-4-iodobenzene 33 as a brownish waxy solid in >99% yield. In the mean time, 5-chlorothiophene-2-carboxylic acid (4, 9.13 g, 56 mmol) was dissolved in 200 mL dry DCM along with 0.5 mL dry DMF. To the vigorously stirred solution was carefully added oxalyl chloride (14.7 mL, 169 mmol) dropwise. The resulting solution was stirred for 3 hrs at RT and concentrated in vacuo. The residue was pumped to dryness and then dissolved in 300 mL dry DCM. To this solution was added propargylamine (5.8 mL, 84 mmol) dropwise. The mixture was stirred at RT for overnight and a lot of solid precipitated out. To this mixture was added 600 mL hexane. The mixture was vigorously stirred for a few hours and filtered for the solid (product 34). The solid (9.47 g, 85%) was washed with hexane and was pure enough for direct use without further purification. MS found for C8H6ClNOS as (M+H)+ 200.0, 202.0. chilled in ice bath The mixture was stirred in ice bath for 1 hr concentrated in vacuo to remove TFA washed with water three times The organic phase was dried concentrated in vacuo

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

Procedure: 4-Iodoaniline (32, 6.00 g, 27.4 mmol) was dissolved in 25 mL TFA and stirred in ice bath. Solid NaNO2 (2.07 g, 30.1 mmol) was added in small portions. The resulting mixture was stirred for 30 min in the ice bath. Sodium azide (1.87 g, 28.8 mmol) was dissolved in 10 mL water and chilled in ice bath. This cold solution was then added to the TFA solution in three portions. The mixture was stirred in ice bath for 1 hr and concentrated in vacuo to remove TFA. The residue was taken into 600 mL DCM and washed with water three times. The organic phase was dried using MgSO4 and concentrated in vacuo to afford 1-azido-4-iodobenzene 33 as a brownish waxy solid in >99% yield. In the mean time, 5-chlorothiophene-2-carboxylic acid (4, 9.13 g, 56 mmol) was dissolved in 200 mL dry DCM along with 0.5 mL dry DMF. To the vigorously stirred solution was carefully added oxalyl chloride (14.7 mL, 169 mmol) dropwise. The resulting solution was stirred for 3 hrs at RT and concentrated in vacuo. The residue was pumped to dryness and then dissolved in 300 mL dry DCM. To this solution was added propargylamine (5.8 mL, 84 mmol) dropwise. The mixture was stirred at RT for overnight and a lot of solid precipitated out. To this mixture was added 600 mL hexane. The mixture was vigorously stirred for a few hours and filtered for the solid (product 34). The solid (9.47 g, 85%) was washed with hexane and was pure enough for direct use without further purification. MS found for C8H6ClNOS as (M+H)+ 200.0, 202.0. chilled in ice bath The mixture was stirred in ice bath for 1 hr concentrated in vacuo to remove TFA washed with water three times The organic phase was dried concentrated in vacuo

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

Procedure: 6 g of p-iodoaniline was dispersed in a solution comprising 25 cc of water and 7.5 cc of 36% hydrochloric acid and cooled with ice. 2.1 g of sodium nitrite was dissolved in 13 ml of water and the resulting solution was added dropwise slowly to the dispersion to effect the diazotization reaction. A solution of 2.5 g of sodium azide in 18 ml of water was added dropwise thereto and, after stirring for one hour, the mixture was subjected to extraction with benzene. After the dehydration with sodium sulfate, benzene was evaporated to obtain p-azidoiodobenzene. cooled with ice the resulting solution was added dropwise slowly to the dispersion the diazotization reaction the mixture was subjected to extraction with benzene After the dehydration with sodium sulfate, benzene was evaporated