2-(4-bromophenyl)propane-1,3-diol

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

Procedure: To a stirred suspension of 2-(4-bromo-phenyl)-propane-1,3-diol (462 mg, 2.00 mmol, JACS, 125(46), 13948) in DCM (50 mL) and Et3N (0.7 mL, 5 mmol) was added MsCl (0.3 mL, 4.0 mmol) at 0° C. The resulting mixture was allowed to warm to RT and stirred for 4 h and treated with satd NaHCO3 (50 mL). The DCM layer was separated and the aq layer was extracted twice with DCM (2×20 mL). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo. The resulting bismesylate was dried under high vacuum for 2 h and redissolved in DMF (5 mL) To this mixture NaN3 (0.52 g, 8.0 mmol) was added. The resulting mixture was heated at 70° C. over night. The reaction mixture was allowed to cool to RT and treated with water (10 mL). The product was then extracted with EtOAc (3×10 mL). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo. The resulting diazide was dried under high vacuum for 2 h and used in next step without further purification. The diazide (280 mg, 1 mmol) was dissolved in MeOH (5 mL) and Et3N (1.4 mL, 10 mmol) and the resulting solution was placed under N2. To this solution propanedithiol (1.0 mL, 10 mmol) was added. The resulting mixture was stirred at RT overnight and concentrated to obtain a viscous oil which was dried under high vacuum for 2 h, dissolved in ether (20 mL) and treated with 2M HCl in ether (10 mL, 20 mmol). The resulting suspension was sonicated for 5 min and stirred for 5 h. The precipitate formed was collected by suction filtration and dried in vacuo to obtain 2-(4-bromo-phenyl)-propane-1,3-diamine dihydrochloride which was directly used in next step without further purification. The dihydrochloride salt (302 mg, 1 mmol) was added to a solution of Et3N (0.7 mL, 5 mmol) and dimethyl N-cyanodithioiminocarbonate (146 mg, 1.00 mmol) in EtOH (10 mL). The resulting mixture was heated at 80° C. overnight. The reaction mixture was allowed to cool to RT and stirred for another 2 h. The precipitate formed was collected by suction filtration to obtain 92 mg (33%) of the title compound. Mass spectrum (ESI, m/z): Calcd. for C11H11BrN4, 279.0 (M+H). found 279.1. The DCM layer was separated the aq layer was extracted twice with DCM (2×20 mL) dried (Na2SO4) concentrated in vacuo The resulting bismesylate was dried under high vacuum for 2 h was added The resulting mixture was heated at 70° C. over night to cool to RT The product was then extracted with EtOAc (3×10 mL) dried (Na2SO4) concentrated in vacuo The resulting diazide was dried under high vacuum for 2 h used in next step without further purification The resulting mixture was stirred at RT overnight concentrated to obtain a viscous oil which was dried under high vacuum for 2 h dissolved in ether (20 mL) The resulting suspension was sonicated for 5 min stirred for 5 h The precipitate formed was collected by suction filtration dried in vacuo

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

Procedure: To a stirred suspension of 2-(4-bromo-phenyl)-propane-1,3-diol (462 mg, 2.00 mmol, JACS, 125(46), 13948) in DCM (50 mL) and Et3N (0.7 mL, 5 mmol) was added MsCl (0.3 mL, 4.0 mmol) at 0° C. The resulting mixture was allowed to warm to RT and stirred for 4 h and treated with satd NaHCO3 (50 mL). The DCM layer was separated and the aq layer was extracted twice with DCM (2×20 mL). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo. The resulting bismesylate was dried under high vacuum for 2 h and redissolved in DMF (5 mL). To this mixture NaN3 (0.52 g, 8.0 mmol) was added. The resulting mixture was heated at 70° C. over night. The reaction mixture was allowed to cool to RT and treated with water (10 mL). The product was then extracted with EtOAc (3×10 mL). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo. The resulting diazide was dried under high vacuum for 2 h and used in next step without further purification. The diazide (280 mg, 1 mmol) was dissolved in MeOH (5 mL) and Et3N (1.4 mL, 10 mmol) and the resulting solution was placed under N2. To this solution propanedithiol (1.0 mL, 10 mmol) was added. The resulting mixture was stirred at RT overnight and concentrated to obtain a viscous oil which was dried under high vacuum for 2 h, dissolved in ether (20 mL) and treated with 2M HCl in ether (10 mL, 20 mmol). The resulting suspension was sonicated for 5 min and stirred for 5 h. The precipitate formed was collected by suction filtration and dried in vacuo to obtain 2-(4-bromo-phenyl)-propane-1,3-diamine dihydrochloride which was directly used in next step without further purification. The dihydrochloride salt (302 mg, 1 mmol) was added to a solution of Et3N (0.7 mL, 5 mmol) and dimethyl N-cyanodithioiminocarbonate (146 mg, 1.00 mmol) in EtOH (10 mL). The resulting mixture was heated at 80° C. overnight. The reaction mixture was allowed to cool to RT and stirred for another 2 h. The precipitate formed was collected by suction filtration to obtain 92 mg (33%) of the title compound. Mass spectrum (ESI, m/z): Calcd. for C11H11BrN4, 279.0 (M+H). found 279.1. The DCM layer was separated the aq layer was extracted twice with DCM (2×20 mL) dried (Na2SO4) concentrated in vacuo The resulting bismesylate was dried under high vacuum for 2 h redissolved in DMF (5 mL) The resulting mixture was heated at 70° C. over night to cool to RT The product was then extracted with EtOAc (3×10 mL) dried (Na2SO4) concentrated in vacuo The resulting diazide was dried under high vacuum for 2 h used in next step without further purification The resulting mixture was stirred at RT overnight concentrated to obtain a viscous oil which was dried under high vacuum for 2 h dissolved in ether (20 mL) The resulting suspension was sonicated for 5 min stirred for 5 h The precipitate formed was collected by suction filtration dried in vacuo

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

Procedure: To a stirred suspension of 2-(4-bromo-phenyl)-propane-1,3-diol (462 mg, 2.00 mmol, JACS, 125(46), 13948) in DCM (50 mL) and Et3N (0.7 mL, 5 mmol) was added MsCl (0.3 mL, 4.0 mmol) at 0° C. The resulting mixture was allowed to warm to RT and stirred for 4 h and treated with satd NaHCO3 (50 mL). The DCM layer was separated and the aq layer was extracted twice with DCM (2×20 mL). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo. The resulting bismesylate was dried under high vacuum for 2 h and redissolved in DMF (5 mL) To this mixture NaN3 (0.52 g, 8.0 mmol) was added. The resulting mixture was heated at 70° C. over night. The reaction mixture was allowed to cool to RT and treated with water (10 mL). The product was then extracted with EtOAc (3×10 mL). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo. The resulting diazide was dried under high vacuum for 2 h and used in next step without further purification. The diazide (280 mg, 1 mmol) was dissolved in MeOH (5 mL) and Et3N (1.4 mL, 10 mmol) and the resulting solution was placed under N2. To this solution propanedithiol (1.0 mL, 10 mmol) was added. The resulting mixture was stirred at RT overnight and concentrated to obtain a viscous oil which was dried under high vacuum for 2 h, dissolved in ether (20 mL) and treated with 2M HCl in ether (10 mL, 20 mmol). The resulting suspension was sonicated for 5 min and stirred for 5 h. The precipitate formed was collected by suction filtration and dried in vacuo to obtain 2-(4-bromo-phenyl)-propane-1,3-diamine dihydrochloride which was directly used in next step without further purification. The dihydrochloride salt (302 mg, 1 mmol) was added to a solution of Et3N (0.7 mL, 5 mmol) and dimethyl N-cyanodithioiminocarbonate (146 mg, 1.00 mmol) in EtOH (10 mL). The resulting mixture was heated at 80° C. overnight. The reaction mixture was allowed to cool to RT and stirred for another 2 h. The precipitate formed was collected by suction filtration to obtain 92 mg (33%) of the title compound. Mass spectrum (ESI, m/z): Calcd. for C11H11BrN4, 279.0 (M+H). found 279.1. The DCM layer was separated the aq layer was extracted twice with DCM (2×20 mL) dried (Na2SO4) concentrated in vacuo The resulting bismesylate was dried under high vacuum for 2 h was added The resulting mixture was heated at 70° C. over night to cool to RT The product was then extracted with EtOAc (3×10 mL) dried (Na2SO4) concentrated in vacuo The resulting diazide was dried under high vacuum for 2 h used in next step without further purification The resulting mixture was stirred at RT overnight concentrated to obtain a viscous oil which was dried under high vacuum for 2 h dissolved in ether (20 mL) The resulting suspension was sonicated for 5 min stirred for 5 h The precipitate formed was collected by suction filtration dried in vacuo

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

Procedure: To a stirred suspension of 2-(4-bromo-phenyl)-propane-1,3-diol (462 mg, 2.00 mmol, JACS, 125(46), 13948) in DCM (50 mL) and Et3N (0.7 mL, 5 mmol) was added MsCl (0.3 mL, 4.0 mmol) at 0° C. The resulting mixture was allowed to warm to RT and stirred for 4 h and treated with satd NaHCO3 (50 mL). The DCM layer was separated and the aq layer was extracted twice with DCM (2×20 mL). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo. The resulting bismesylate was dried under high vacuum for 2 h and redissolved in DMF (5 mL) To this mixture NaN3 (0.52 g, 8.0 mmol) was added. The resulting mixture was heated at 70° C. over night. The reaction mixture was allowed to cool to RT and treated with water (10 mL). The product was then extracted with EtOAc (3×10 mL). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo. The resulting diazide was dried under high vacuum for 2 h and used in next step without further purification. The diazide (280 mg, 1 mmol) was dissolved in MeOH (5 mL) and Et3N (1.4 mL, 10 mmol) and the resulting solution was placed under N2. To this solution propanedithiol (1.0 mL, 10 mmol) was added. The resulting mixture was stirred at RT overnight and concentrated to obtain a viscous oil which was dried under high vacuum for 2 h, dissolved in ether (20 mL) and treated with 2M HCl in ether (10 mL, 20 mmol). The resulting suspension was sonicated for 5 min and stirred for 5 h. The precipitate formed was collected by suction filtration and dried in vacuo to obtain 2-(4-bromo-phenyl)-propane-1,3-diamine dihydrochloride which was directly used in next step without further purification. The dihydrochloride salt (302 mg, 1 mmol) was added to a solution of Et3N (0.7 mL, 5 mmol) and dimethyl N-cyanodithioiminocarbonate (146 mg, 1.00 mmol) in EtOH (10 mL). The resulting mixture was heated at 80° C. overnight. The reaction mixture was allowed to cool to RT and stirred for another 2 h. The precipitate formed was collected by suction filtration to obtain 92 mg (33%) of the title compound. Mass spectrum (ESI, m/z): Calcd. for C11H11BrN4, 279.0 (M+H). found 279.1. The DCM layer was separated the aq layer was extracted twice with DCM (2×20 mL) dried (Na2SO4) concentrated in vacuo The resulting bismesylate was dried under high vacuum for 2 h was added The resulting mixture was heated at 70° C. over night to cool to RT The product was then extracted with EtOAc (3×10 mL) dried (Na2SO4) concentrated in vacuo The resulting diazide was dried under high vacuum for 2 h used in next step without further purification The resulting mixture was stirred at RT overnight concentrated to obtain a viscous oil which was dried under high vacuum for 2 h dissolved in ether (20 mL) The resulting suspension was sonicated for 5 min stirred for 5 h The precipitate formed was collected by suction filtration dried in vacuo

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

Procedure: To a stirred suspension of 2-(4-bromo-phenyl)-propane-1,3-diol (462 mg, 2.00 mmol, JACS, 125(46), 13948) in DCM (50 mL) and Et3N (0.7 mL, 5 mmol) was added MsCl (0.3 mL, 4.0 mmol) at 0° C. The resulting mixture was allowed to warm to RT and stirred for 4 h and treated with satd NaHCO3 (50 mL). The DCM layer was separated and the aq layer was extracted twice with DCM (2×20 mL). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo. The resulting bismesylate was dried under high vacuum for 2 h and redissolved in DMF (5 mL) To this mixture NaN3 (0.52 g, 8.0 mmol) was added. The resulting mixture was heated at 70° C. over night. The reaction mixture was allowed to cool to RT and treated with water (10 mL). The product was then extracted with EtOAc (3×10 mL). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo. The resulting diazide was dried under high vacuum for 2 h and used in next step without further purification. The diazide (280 mg, 1 mmol) was dissolved in MeOH (5 mL) and Et3N (1.4 mL, 10 mmol) and the resulting solution was placed under N2. To this solution propanedithiol (1.0 mL, 10 mmol) was added. The resulting mixture was stirred at RT overnight and concentrated to obtain a viscous oil which was dried under high vacuum for 2 h, dissolved in ether (20 mL) and treated with 2M HCl in ether (10 mL, 20 mmol). The resulting suspension was sonicated for 5 min and stirred for 5 h. The precipitate formed was collected by suction filtration and dried in vacuo to obtain 2-(4-bromo-phenyl)-propane-1,3-diamine dihydrochloride which was directly used in next step without further purification. The dihydrochloride salt (302 mg, 1 mmol) was added to a solution of Et3N (0.7 mL, 5 mmol) and dimethyl N-cyanodithioiminocarbonate (146 mg, 1.00 mmol) in EtOH (10 mL). The resulting mixture was heated at 80° C. overnight. The reaction mixture was allowed to cool to RT and stirred for another 2 h. The precipitate formed was collected by suction filtration to obtain 92 mg (33%) of the title compound. Mass spectrum (ESI, m/z): Calcd. for C11H11BrN4, 279.0 (M+H). found 279.1. The DCM layer was separated the aq layer was extracted twice with DCM (2×20 mL) dried (Na2SO4) concentrated in vacuo The resulting bismesylate was dried under high vacuum for 2 h was added The resulting mixture was heated at 70° C. over night to cool to RT The product was then extracted with EtOAc (3×10 mL) dried (Na2SO4) concentrated in vacuo The resulting diazide was dried under high vacuum for 2 h used in next step without further purification The resulting mixture was stirred at RT overnight concentrated to obtain a viscous oil which was dried under high vacuum for 2 h dissolved in ether (20 mL) The resulting suspension was sonicated for 5 min stirred for 5 h The precipitate formed was collected by suction filtration dried in vacuo

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

Procedure: To a solution of 2-(4-bromophenyl)propane-1,3-diol (9.01 g, 39.0 mmol) in vinyl acetate (100 ml) was added Lipase AK Amano (purchased from WAKO, 12.0 g) at room temperature. The mixture was stirred at room temperature for 11 hours and filtered through a pad of Celite to remove solid materials. After concentration, to the residue dissolved into ethanol (35 ml) and diisopropyl ether (200 ml) was added Lipase from porcine pancreas (type II, purchased from SIGMA, 22.2 g). The mixture was stirred at room temperature for 107 hours and filtered through a pad of Celite. The filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (eluant: hexane/ethyl acetate=2/1) to afford (−)-2-(4-bromophenyl)-3-hydroxypropyl acetate as colorless oil (6.88 g, 65%). [α]D=−11.2 (C=0.5, CHCl3). filtered through a pad of Celite to remove solid materials After concentration to the residue dissolved into ethanol (35 ml) and diisopropyl ether (200 ml) was added Lipase from porcine pancreas (type II, purchased from SIGMA, 22.2 g) The mixture was stirred at room temperature for 107 hours filtered through a pad of Celite The filtrate was concentrated in vacuo The residue was purified by silica gel column chromatography (eluant: hexane/ethyl acetate=2/1)

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

Procedure: To a solution of 2-(4-bromophenyl)propane-1,3-diol (9.01 g, 39.0 mmol) in vinyl acetate (100 ml) was added Lipase AK Amano (purchased from WAKO, 12.0 g) at room temperature. The mixture was stirred at room temperature for 11 hours and filtered through a pad of Celite to remove solid materials. After concentration, to the residue dissolved into ethanol (35 ml) and diisopropyl ether (200 ml) was added Lipase from porcine pancreas (type II, purchased from SIGMA, 22.2 g). The mixture was stirred at room temperature for 107 hours and filtered through a pad of Celite. The filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (eluant: hexane/ethyl acetate=2/1) to afford (−)-2-(4-bromophenyl)-3-hydroxypropyl acetate as colorless oil (6.88 g, 65%). [α]D=−11.2 (C=0.5, CHCl3). filtered through a pad of Celite to remove solid materials After concentration to the residue dissolved into ethanol (35 ml) and diisopropyl ether (200 ml) was added Lipase from porcine pancreas (type II, purchased from SIGMA, 22.2 g) The mixture was stirred at room temperature for 107 hours filtered through a pad of Celite The filtrate was concentrated in vacuo The residue was purified by silica gel column chromatography (eluant: hexane/ethyl acetate=2/1)

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

Procedure: To a solution of diethyl 2-(4-bromophenyl)malonate (18.1 g, 57.5 mmol) in ether (285 ml) was added 0.98M-diisobutylaluminium hydride in hexane (259 ml, 254 mmol) at 0° C. under nitrogen atmosphere. The resulting mixture was stirred at 0° C. for 4 hours. Aqueous potassium sodium tartrate (0.57M, 500 ml) was added to the reaction mixture for quenching the aluminum reagent and the mixture was stirred for 14 hours. The organic layer was extracted with ethyl acetate and dried over sodium sulfate. After concentration, the residue was purified by silica gel column chromatography (eluant: hexane/ethyl acetate=40/60 to ethyl acetate only) to afford 2-(4-bromophenyl)propane-1,3-diol as white solid (4.97 g, 37%). for quenching the aluminum reagent the mixture was stirred for 14 hours The organic layer was extracted with ethyl acetate dried over sodium sulfate After concentration the residue was purified by silica gel column chromatography (eluant

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

Procedure: To a stirred suspension of 2-(4-bromo-phenyl)-propane-1,3-diol (462 mg, 2.00 mmol, JACS, 125(46), 13948) in DCM (50 mL) and Et3N (0.7 mL, 5 mmol) was added MsCl (0.3 mL, 4.0 mmol) at 0° C. The resulting mixture was allowed to warm to RT and stirred for 4 h and treated with satd NaHCO3 (50 mL). The DCM layer was separated and the aq layer was extracted twice with DCM (2×20 mL). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo. The resulting bismesylate was dried under high vacuum for 2 h and redissolved in DMF (5 mL) To this mixture NaN3 (0.52 g, 8.0 mmol) was added. The resulting mixture was heated at 70° C. over night. The reaction mixture was allowed to cool to RT and treated with water (10 mL). The product was then extracted with EtOAc (3×10 mL). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo. The resulting diazide was dried under high vacuum for 2 h and used in next step without further purification. The diazide (280 mg, 1 mmol) was dissolved in MeOH (5 mL) and Et3N (1.4 mL, 10 mmol) and the resulting solution was placed under N2. To this solution propanedithiol (1.0 mL, 10 mmol) was added. The resulting mixture was stirred at RT overnight and concentrated to obtain a viscous oil which was dried under high vacuum for 2 h, dissolved in ether (20 mL) and treated with 2M HCl in ether (10 mL, 20 mmol). The resulting suspension was sonicated for 5 min and stirred for 5 h. The precipitate formed was collected by suction filtration and dried in vacuo to obtain 2-(4-bromo-phenyl)-propane-1,3-diamine dihydrochloride which was directly used in next step without further purification. The dihydrochloride salt (302 mg, 1 mmol) was added to a solution of Et3N (0.7 mL, 5 mmol) and dimethyl N-cyanodithioiminocarbonate (146 mg, 1.00 mmol) in EtOH (10 mL). The resulting mixture was heated at 80° C. overnight. The reaction mixture was allowed to cool to RT and stirred for another 2 h. The precipitate formed was collected by suction filtration to obtain 92 mg (33%) of the title compound. Mass spectrum (ESI, m/z): Calcd. for C11H11BrN4, 279.0 (M+H), found 279.1. The DCM layer was separated the aq layer was extracted twice with DCM (2×20 mL) dried (Na2SO4) concentrated in vacuo The resulting bismesylate was dried under high vacuum for 2 h was added The resulting mixture was heated at 70° C. over night to cool to RT The product was then extracted with EtOAc (3×10 mL) dried (Na2SO4) concentrated in vacuo The resulting diazide was dried under high vacuum for 2 h used in next step without further purification The resulting mixture was stirred at RT overnight concentrated to obtain a viscous oil which was dried under high vacuum for 2 h dissolved in ether (20 mL) The resulting suspension was sonicated for 5 min stirred for 5 h The precipitate formed was collected by suction filtration dried in vacuo

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

Procedure: To a stirred suspension of 2-(4-bromo-phenyl)-propane-1,3-diol (462 mg, 2.00 mmol, JACS, 125(46), 13948) in DCM (50 mL) and Et3N (0.7 mL, 5 mmol) was added MsCl (0.3 mL, 4.0 mmol) at 0° C. The resulting mixture was allowed to warm to RT and stirred for 4 h and treated with satd NaHCO3 (50 mL). The DCM layer was separated and the aq layer was extracted twice with DCM (2×20 mL). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo. The resulting bismesylate was dried under high vacuum for 2 h and redissolved in DMF (5 mL) To this mixture NaN3 (0.52 g, 8.0 mmol) was added. The resulting mixture was heated at 70° C. over night. The reaction mixture was allowed to cool to RT and treated with water (10 mL). The product was then extracted with EtOAc (3×10 mL). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo. The resulting diazide was dried under high vacuum for 2 h and used in next step without further purification. The diazide (280 mg, 1 mmol) was dissolved in MeOH (5 mL) and Et3N (1.4 mL, 10 mmol) and the resulting solution was placed under N2. To this solution propanedithiol (1.0 mL, 10 mmol) was added. The resulting mixture was stirred at RT overnight and concentrated to obtain a viscous oil which was dried under high vacuum for 2 h, dissolved in ether (20 mL) and treated with 2M HCl in ether (10 mL, 20 mmol). The resulting suspension was sonicated for 5 min and stirred for 5 h. The precipitate formed was collected by suction filtration and dried in vacuo to obtain 2-(4-bromo-phenyl)-propane-1,3-diamine dihydrochloride which was directly used in next step without further purification. The dihydrochloride salt (302 mg, 1 mmol) was added to a solution of Et3N (0.7 mL, 5 mmol) and dimethyl N-cyanodithioiminocarbonate (146 mg, 1.00 mmol) in EtOH (10 mL). The resulting mixture was heated at 80° C. overnight. The reaction mixture was allowed to cool to RT and stirred for another 2 h. The precipitate formed was collected by suction filtration to obtain 92 mg (33%) of the title compound. Mass spectrum (ESI, m/z): Calcd. for C11H11BrN4, 279.0 (M+H). found 279.1. The DCM layer was separated the aq layer was extracted twice with DCM (2×20 mL) dried (Na2SO4) concentrated in vacuo The resulting bismesylate was dried under high vacuum for 2 h was added The resulting mixture was heated at 70° C. over night to cool to RT The product was then extracted with EtOAc (3×10 mL) dried (Na2SO4) concentrated in vacuo The resulting diazide was dried under high vacuum for 2 h used in next step without further purification The resulting mixture was stirred at RT overnight concentrated to obtain a viscous oil which was dried under high vacuum for 2 h dissolved in ether (20 mL) The resulting suspension was sonicated for 5 min stirred for 5 h The precipitate formed was collected by suction filtration dried in vacuo

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

Procedure: To a stirred suspension of 2-(4-bromo-phenyl)-propane-1,3-diol (462 mg, 2.00 mmol, JACS, 125(46), 13948) in DCM (50 mL) and Et3N (0.7 mL, 5 mmol) was added MsCl (0.3 mL, 4.0 mmol) at 0° C. The resulting mixture was allowed to warm to RT and stirred for 4 h and treated with satd NaHCO3 (50 mL). The DCM layer was separated and the aq layer was extracted twice with DCM (2×20 mL). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo. The resulting bismesylate was dried under high vacuum for 2 h and redissolved in DMF (5 mL). To this mixture NaN3 (0.52 g, 8.0 mmol) was added. The resulting mixture was heated at 70° C. over night. The reaction mixture was allowed to cool to RT and treated with water (10 mL). The product was then extracted with EtOAc (3×10 mL). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo. The resulting diazide was dried under high vacuum for 2 h and used in next step without further purification. The diazide (280 mg, 1 mmol) was dissolved in MeOH (5 mL) and Et3N (1.4 mL, 10 mmol) and the resulting solution was placed under N2. To this solution propanedithiol (1.0 mL, 10 mmol) was added. The resulting mixture was stirred at RT overnight and concentrated to obtain a viscous oil which was dried under high vacuum for 2 h, dissolved in ether (20 mL) and treated with 2M HCl in ether (10 mL, 20 mmol). The resulting suspension was sonicated for 5 min and stirred for 5 h. The precipitate formed was collected by suction filtration and dried in vacuo to obtain 2-(4-bromo-phenyl)-propane-1,3-diamine dihydrochloride which was directly used in next step without further purification. The dihydrochloride salt (302 mg, 1 mmol) was added to a solution of Et3N (0.7 mL, 5 mmol) and dimethyl N-cyanodithioiminocarbonate (146 mg, 1.00 mmol) in EtOH (10 mL). The resulting mixture was heated at 80° C. overnight. The reaction mixture was allowed to cool to RT and stirred for another 2 h. The precipitate formed was collected by suction filtration to obtain 92 mg (33%) of the title compound. Mass spectrum (ESI, m/z): Calcd. for C11H11BrN4, 279.0 (M+H). found 279.1. The DCM layer was separated the aq layer was extracted twice with DCM (2×20 mL) dried (Na2SO4) concentrated in vacuo The resulting bismesylate was dried under high vacuum for 2 h redissolved in DMF (5 mL) The resulting mixture was heated at 70° C. over night to cool to RT The product was then extracted with EtOAc (3×10 mL) dried (Na2SO4) concentrated in vacuo The resulting diazide was dried under high vacuum for 2 h used in next step without further purification The resulting mixture was stirred at RT overnight concentrated to obtain a viscous oil which was dried under high vacuum for 2 h dissolved in ether (20 mL) The resulting suspension was sonicated for 5 min stirred for 5 h The precipitate formed was collected by suction filtration dried in vacuo

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

Procedure: To a stirred suspension of 2-(4-bromo-phenyl)-propane-1,3-diol (462 mg, 2.00 mmol, JACS, 125(46), 13948) in DCM (50 mL) and Et3N (0.7 mL, 5 mmol) was added MsCl (0.3 mL, 4.0 mmol) at 0° C. The resulting mixture was allowed to warm to RT and stirred for 4 h and treated with satd NaHCO3 (50 mL). The DCM layer was separated and the aq layer was extracted twice with DCM (2×20 mL). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo. The resulting bismesylate was dried under high vacuum for 2 h and redissolved in DMF (5 mL). To this mixture NaN3 (0.52 g, 8.0 mmol) was added. The resulting mixture was heated at 70° C. over night. The reaction mixture was allowed to cool to RT and treated with water (10 mL). The product was then extracted with EtOAc (3×10 mL). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo. The resulting diazide was dried under high vacuum for 2 h and used in next step without further purification. The diazide (280 mg, 1 mmol) was dissolved in MeOH (5 mL) and Et3N (1.4 mL, 10 mmol) and the resulting solution was placed under N2. To this solution propanedithiol (1.0 mL, 10 mmol) was added. The resulting mixture was stirred at RT overnight and concentrated to obtain a viscous oil which was dried under high vacuum for 2 h, dissolved in ether (20 mL) and treated with 2M HCl in ether (10 mL, 20 mmol). The resulting suspension was sonicated for 5 min and stirred for 5 h. The precipitate formed was collected by suction filtration and dried in vacuo to obtain 2-(4-bromo-phenyl)-propane-1,3-diamine dihydrochloride which was directly used in next step without further purification. The dihydrochloride salt (302 mg, 1 mmol) was added to a solution of Et3N (0.7 mL, 5 mmol) and dimethyl N-cyanodithioiminocarbonate (146 mg, 1.00 mmol) in EtOH (10 mL). The resulting mixture was heated at 80° C. overnight. The reaction mixture was allowed to cool to RT and stirred for another 2 h. The precipitate formed was collected by suction filtration to obtain 92 mg (33%) of the title compound. Mass spectrum (ESI, m/z): Calcd. for C11H11BrN4, 279.0 (M+H). found 279.1. The DCM layer was separated the aq layer was extracted twice with DCM (2×20 mL) dried (Na2SO4) concentrated in vacuo The resulting bismesylate was dried under high vacuum for 2 h redissolved in DMF (5 mL) The resulting mixture was heated at 70° C. over night to cool to RT The product was then extracted with EtOAc (3×10 mL) dried (Na2SO4) concentrated in vacuo The resulting diazide was dried under high vacuum for 2 h used in next step without further purification The resulting mixture was stirred at RT overnight concentrated to obtain a viscous oil which was dried under high vacuum for 2 h dissolved in ether (20 mL) The resulting suspension was sonicated for 5 min stirred for 5 h The precipitate formed was collected by suction filtration dried in vacuo