3-azidopropan-1-amine

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

Procedure: FIG. 6 is a series of schemes showing the synthesis of the monomers used in the adhesives test. The first reaction to make 1 is an N-sulfonylation of the nitrogen mustard, N,N-di(2-chloroethyl) amine, followed by an SN2 displacement of the chlorides to obtain the diazide, 1. The second reaction is an N-propargylation of 4-methyl-benzenesulfonamide under mild conditions to give the diacetylene, 2. The last reaction is the displacement of the chlorides of cyanuric chloride with 3-azidopropylamine to give the triamino-1,3,5-triazine 5. The last reaction

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

Procedure: To a solution of (14S,18S)-tri-tert-butyl 1-(1-(2-(tert-butoxy)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2-(4-(prop-2-yn-1-yloxy)benzyl)-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate (250 mg, 0.266 mmol) and 3-azidopropan-1-amine (200 mg, 2.0 mmol) in THF (5.0 mL) and water (1.0 mL) was added copper powder (17 mg) and 1 N CuSO4 (0.05 mL). The mixture was stirred at room temperature for 6 hrs under nitrogen, diluted with DCM, washed with aqueous saturated solution of EDTA. The solvent was evaporated under reduce pressure to afford a residue, which was purified by Biotage SP4 to afford (14S,18S)-tri-tert-butyl 2-(4-((1-(3-aminopropyl)-1H-1,2,3-triazol-4-yl)methoxy)benzyl)-1-(1-(2-(tert-butoxy)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate (158 mg, 57%) as a yellow oil. MS (ESI), 520.4 (M/2+H)+. washed with aqueous saturated solution of EDTA The solvent was evaporated to afford a residue, which was purified by Biotage SP4

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

Procedure: To a solution of (14S,18S)-tri-tert-butyl 1-(1-(2-(tert-butoxy)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2-(4-(prop-2-yn-1-yloxy)benzyl)-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate (250 mg, 0.266 mmol) and 3-azidopropan-1-amine (200 mg, 2.0 mmol) in THF (5.0 mL) and water (1.0 mL) was added copper powder (17 mg) and 1 N CuSO4 (0.05 mL). The mixture was stirred at room temperature for 6 hrs under nitrogen, diluted with DCM, washed with aqueous saturated solution of EDTA. The solvent was evaporated under reduce pressure to afford a residue, which was purified by Biotage SP4 to afford (14S,18S)-tri-tert-butyl 2-(4-((1-(3-aminopropyl)-1H-1,2,3-triazol-4-yl)methoxy)benzyl)-1-(1-(2-(tert-butoxy)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate (158 mg, 57%) as a yellow oil. MS (ESI), 520.4 (M/2+H)+. washed with aqueous saturated solution of EDTA The solvent was evaporated to afford a residue, which was purified by Biotage SP4

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

Procedure: To a solution of (14S,18S)-tri-tert-butyl 1-(1-(2-(bis(2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2-(4-(prop-2-yn-1-yloxy)benzyl)-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate (65 mg, 0.0586 mmol) and 3-azidopropan-1-amine (200 mg, 2.0 mmol) in THF (2.0 mL) and water (0.5 mL) was added copper powder (10 mg) and 1 N CuSO4 (0.05 mL). The mixture was stirred at room temperature for 2 h under nitrogen, diluted with DCM and washed with an aqueous saturated solution of EDTA. The solvent was evaporated under reduce pressure to afford a residue, which was purified by Biotage SP4 to afford (14S,18S)-tri-tert-butyl 2-(4-((1-(3-aminopropyl)-1H-1,2,3-triazol-4-yl)methoxy)benzyl)-1-(1-(2-(bis(2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate (17.5 mg, 25%). MS (ESI), 605.8 (M/2+H)′. washed with an aqueous saturated solution of EDTA The solvent was evaporated to afford a residue, which was purified by Biotage SP4

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

Procedure: FIG. 6 is a series of schemes showing the synthesis of the monomers used in the adhesives test. The first reaction to make 1 is an N-sulfonylation of the nitrogen mustard, N,N-di(2-chloroethyl) amine, followed by an SN2 displacement of the chlorides to obtain the diazide, 1. The second reaction is an N-propargylation of 4-methyl-benzenesulfonamide under mild conditions to give the diacetylene, 2. The last reaction is the displacement of the chlorides of cyanuric chloride with 3-azidopropylamine to give the triamino-1,3,5-triazine 5. The last reaction

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

Procedure: To a solution of (14S,18S)-tri-tert-butyl 1-(1-(2-(tert-butoxy)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2-(4-(prop-2-yn-1-yloxy)benzyl)-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate (250 mg, 0.266 mmol) and 3-azidopropan-1-amine (200 mg, 2.0 mmol) in THF (5.0 mL) and water (1.0 mL) was added copper powder (17 mg) and 1 N CuSO4 (0.05 mL). The mixture was stirred at room temperature for 6 hrs under nitrogen, diluted with DCM, washed with aqueous saturated solution of EDTA. The solvent was evaporated under reduce pressure to afford a residue, which was purified by Biotage SP4 to afford (14S,18S)-tri-tert-butyl 2-(4-((1-(3-aminopropyl)-1H-1,2,3-triazol-4-yl)methoxy)benzyl)-1-(1-(2-(tert-butoxy)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate (158 mg, 57%) as a yellow oil. MS (ESI), 520.4 (M/2-41)+. washed with aqueous saturated solution of EDTA The solvent was evaporated to afford a residue, which was purified by Biotage SP4

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

Procedure: To a solution of (14S,18S)-tri-tert-butyl 1-(1-(2-(bis(2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2-(4-(prop-2-yn-1-yloxy)benzyl)-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate (65 mg, 0.0586 mmol) and 3-azidopropan-1-amine (200 mg, 2.0 mmol) in THF (2.0 mL) and water (0.5 mL) was added copper powder (10 mg) and 1 N CuSO4 (0.05 mL). The mixture was stirred at room temperature for 2 h under nitrogen, diluted with DCM and washed with an aqueous saturated solution of EDTA. The solvent was evaporated under reduce pressure to afford a residue, which was purified by Biotage SP4 to afford (14S,18S)-tri-tert-butyl 2-(4-((1-(3-aminopropyl)-1H-1,2,3-triazol-4-yl)methoxy)benzyl)-1-(1-(2-(bis(2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate (17.5 mg, 25%). MS (ESI), 605.8 (M/2+H)+. washed with an aqueous saturated solution of EDTA The solvent was evaporated to afford a residue, which was purified by Biotage SP4

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

Procedure: To a solution of (14S,18S)-tri-tert-butyl 1-(1-(2-(tert-butoxy)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2-(4-(prop-2-yn-1-yloxy)benzyl)-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate (250 mg, 0.266 mmol) and 3-azidopropan-1-amine (200 mg, 2.0 mmol) in THF (5.0 mL) and water (1.0 mL) was added copper powder (17 mg) and 1 N CuSO4 (0.05 mL). The mixture was stirred at room temperature for 6 hrs under nitrogen, diluted with DCM, washed with aqueous saturated solution of EDTA. The solvent was evaporated under reduce pressure to afford a residue, which was purified by Biotage SP4 to afford (14S,18S)-tri-tert-butyl 2-(4-((1-(3-aminopropyl)-1H-1,2,3-triazol-4-yl)methoxy)benzyl)-1-(1-(2-(tert-butoxy)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate (158 mg, 57%) as a yellow oil. MS (ESI), 520.4 (M/2+H)+. washed with aqueous saturated solution of EDTA The solvent was evaporated to afford a residue, which was purified by Biotage SP4

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

Procedure: To a solution of cyanuric chloride (18.42 g, 0.10 mol) in acetone (180 mL) in an ice-water bath was added diisopropylethylamine (DIPEA) (12.92 g, 0.10 mol). 1-azido-3-aminopropane (5.00 g, 0.050 mol) in acetone (50 mL) was added slowly over 2 hours. The reaction was stirred at room temperature overnight. The solvent was removed under reduced pressure. The residue was dissolved in CH2Cl2, washed with water, dried (Na2SO4) and rotary evaporated. The resulting residue was purified by column chromatography on silica gel (eluent CH2Cl2) to give 1 as a white solid (5.62 g, 45%): ESI-MS m/z 248.1 (M+H+) calculated for C6H8Cl2N7 248.0. The solvent was removed under reduced pressure The residue was dissolved in CH2Cl2 washed with water dried (Na2SO4) and rotary evaporated The resulting residue was purified by column chromatography on silica gel (eluent CH2Cl2)

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

Procedure: To a solution of (14S,18S)-tri-tert-butyl 1-(1-(2-(bis(2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2-(4-(prop-2-yn-1-yloxy)benzyl)-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate (65 mg, 0.0586 mmol) and 3-azidopropan-1-amine (200 mg, 2.0 mmol) in THF (2.0 mL) and water (0.5 mL) was added copper powder (10 mg) and 1 N CuSO4 (0.05 mL). The mixture was stirred at room temperature for 2 h under nitrogen, diluted with DCM and washed with an aqueous saturated solution of EDTA. The solvent was evaporated under reduce pressure to afford a residue, which was purified by Biotage SP4 to afford (14S,18S)-tri-tert-butyl 2-(4-((1-(3-aminopropyl)-1H-1,2,3-triazol-4-yl)methoxy)benzyl)-1-(1-(2-(bis(2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-8,16-dioxo-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate (17.5 mg, 25%). MS (ESI), 605.8 (M/2+H)′. washed with an aqueous saturated solution of EDTA The solvent was evaporated to afford a residue, which was purified by Biotage SP4

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

Procedure: FIG. 6 is a series of schemes showing the synthesis of the monomers used in the adhesives test. The first reaction to make 1 is an N-sulfonylation of the nitrogen mustard, N,N-di(2-chloroethyl) amine, followed by an SN2 displacement of the chlorides to obtain the diazide, 1. The second reaction is an N-propargylation of 4-methyl-benzenesulfonamide under mild conditions to give the diacetylene, 2. The last reaction is the displacement of the chlorides of cyanuric chloride with 3-azidopropylamine to give the triamino-1,3,5-triazine 5. The last reaction