tert-butyl N-[amino-[(2-methylpropan-2-yl)oxycarbonylamino]methylidene]carbamate

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

Procedure: The N′,N″-di-BOCguanidine (0.45 g, 0.60 mmol) was dissolvedin CH2Cl2 (10 mL), diluted with dry EtOH (15 mL) and the chilled solution was saturated with dry HCl. The reaction was then kept stirring at room temperature for 3 days (drying tube), when by the product started forming a precipitate over time. After evaporating the solvent to dryness, the residue was washed with ether multiple times and was dried under vacuum at 50-60° C. over night to give whitish yellow solid of the bis-guanidine dihydrochloride; mp>300° C. 1H NMR (DMSO-d6): δ 7.85 (dd, J=1.5, 8.4 Hz, 4H), 7.92 (d, J=1.2 Hz, 4H), 8.00 (dd, J=1.5, 8.4 Hz, 4H ), 9.09 (br s, 4H), 11.25 (br s, 2H). 13C NMR (DMSO-d6): δ 155.98, 138.35, 137.32, 135.00, 127.79, 127.22, 124.79. MS (ESI) m/e (rel. int.): 344 (M+, 6), 173 (100). Anal. Calc. for C20H20N6-2.0HCl-1.0H2O-0.2C2H5OH: C %, 55.11; H %, 5.71; N %, 18.90. Found C %, 55.39; H %, 5.50; N %, 18.71. (drying tube), when by the product started forming a precipitate over time After evaporating the solvent to dryness the residue was washed with ether multiple times was dried under vacuum at 50-60° C. over night

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

Procedure: The N′,N″-di-BOCguanidine (0.45 g, 0.60 mmol) was dissolvedin CH2Cl2 (10 mL), diluted with dry EtOH (15 mL) and the chilled solution was saturated with dry HCl. The reaction was then kept stirring at room temperature for 3 days (drying tube), when by the product started forming a precipitate over time. After evaporating the solvent to dryness, the residue was washed with ether multiple times and was dried under vacuum at 50-60° C. over night to give whitish yellow solid of the bis-guanidine dihydrochloride; mp>300° C. 1H NMR (DMSO-d6): δ 7.85 (dd, J=1.5, 8.4 Hz, 4H), 7.92 (d, J=1.2 Hz, 4H), 8.00 (dd, J=1.5, 8.4 Hz, 4H ), 9.09 (br s, 4H), 11.25 (br s, 2H). 13C NMR (DMSO-d6): δ 155.98, 138.35, 137.32, 135.00, 127.79, 127.22, 124.79. MS (ESI) m/e (rel. int.): 344 (M+, 6), 173 (100). Anal. Calc. for C20H20N6-2.0HCl-1.0H2O-0.2C2H5OH: C %, 55.11; H %, 5.71; N %, 18.90. Found C %, 55.39; H %, 5.50; N %, 18.71. (drying tube), when by the product started forming a precipitate over time After evaporating the solvent to dryness the residue was washed with ether multiple times was dried under vacuum at 50-60° C. over night

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

Procedure: The N′,N″-di-BOCguanidine (0.45 g, 0.60 mmol) was dissolved in CH2Cl2 (10 mL), diluted with dry EtOH (15 mL) and the chilled solution was saturated with dry HCl. The reaction was then kept stirring at room temperature for 3 days (drying tube), when by the product started forming a precipitate over time. After evaporating the solvent to dryness, the residue was washed with ether multiple times and was dried under vacuum at 50-60° C. over night to give whitish yellow solid of the bis-guanidine dihydrochloride; mp>300° C. 1H NMR (DMSO-d6): δ 7.85 (dd, J=1.5, 8.4 Hz, 4H), 7.92 (d, J=1.2 Hz, 4H), 8.00 (dd, J=1.5, 8.4 Hz, 4H), 9.09 (br s, 4H), 11.25 (br s, 2H). 13C NMR (DMSO-d6): δ 155.98, 138.35, 137.32, 135.00, 127.79, 127.22, 124.79. MS (ESI) m/e (rel. int.): 344 (M+, 6), 173 (100). Anal. Calc. for C20H20N6-2.0HCl-1.0H2O-0.2C2H5OH: C %, 55.11; H %, 5.71; N %, 18.90; Found. C %, 55.39; H %, 5.50; N %, 18.71. (drying tube), when by the product started forming a precipitate over time After evaporating the solvent to dryness the residue was washed with ether multiple times was dried under vacuum at 50-60° C. over night

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

Procedure: The N′,N″-di-BOCguanidine (0.45 g, 0.60 mmol) was dissolved in CH2Cl2 (10 mL), diluted with dry EtOH (15 mL) and the chilled solution was saturated with dry HCl. The reaction was then kept stirring at room temperature for 3 days (drying tube), when by the product started forming a precipitate over time. After evaporating the solvent to dryness, the residue was washed with ether multiple times and was dried under vacuum at 50-60° C. over night to give whitish yellow solid of the bis-guanidine dihydrochloride; mp>300° C. 1H NMR (DMSO-d6): δ 7.85 (dd, J=1.5, 8.4 Hz, 4H), 7.92 (d, J=1.2 Hz, 4H), 8.00 (dd, J=1.5, 8.4 Hz, 4H), 9.09 (br s, 4H), 11.25 (br s, 2H). 13C NMR (DMSO-d6): δ 155.98, 138.35, 137.32, 135.00, 127.79, 127.22, 124.79. MS (ESI) m/e (rel. int.): 344 (M+, 6), 173 (100). Anal. Calc. for C20H20N6-2.0HCl-1.0H2O-0.2C2H5OH: C %, 55.11; H %, 5.71; N %, 18.90; Found. C %, 55.39; H %, 5.50; N %, 18.71. (drying tube), when by the product started forming a precipitate over time After evaporating the solvent to dryness the residue was washed with ether multiple times was dried under vacuum at 50-60° C. over night

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

Procedure: The N′,N″-di-BOCguanidine (0.45 g, 0.60 mmol) was dissolved in CH2Cl2 (10 mL), diluted with dry EtOH (15 mL) and the chilled solution was saturated with dry HCl. The reaction was then kept stirring at room temperature for 3 days (drying tube), when by the product started forming a precipitate over time. After evaporating the solvent to dryness, the residue was washed with ether multiple times and was dried under vacuum at 50-60° C. over night to give whitish yellow solid of the bis-guanidine dihydrochloride; mp >300° C. 1H NMR (DMSO-d6): δ 7.85 (dd, J=1.5, 8.4 Hz, 4H), 7.92 (d, J=1.2 Hz, 4H), 8.00 (dd, J=1.5, 8.4 Hz, 4H), 9.09 (br s, 4H), 11.25 (br s, 2H). 13C NMR (DMSO-d6): δ 155.98, 138.35, 137.32, 135.00, 127.79, 127.22, 124.79. MS (ESI) m/e (rel. int.): 344 (M+, 6), 173 (100). Anal. Calc. for C20H20N6-2.0HCl-1.0H2O-0.2C2H5OH: C %, 55.11; H %, 5.71; N %, 18.90. Found C %, 55.39; H %, 5.50; N %, 18.71. (drying tube), when by the product started forming a precipitate over time After evaporating the solvent to dryness the residue was washed with ether multiple times was dried under vacuum at 50-60° C. over night

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

Procedure: To a mixture of methyl 5-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-2-(3-hydroxypropyl)benzoate (90 mg, 0.15 mmol, 1.0 eq), tert-butyl amino(tert-butoxycarbonylamino)methylenecarbamate (76 mg, 0.29 mmol, 2.0 eq) and triphenylphosphine (59 mg, 0.22 mmol, 1.5 eq) in tetrahydrofuran (0.7 mL) was added diisopropylazodicarboxylate (0.04 mL, 0.22 mmol, 1.5 eq). After stirring for 16 h, the reaction mixture was directly poured onto silica gel and purified (0 to 75% ethyl acetate/hexanes). This product was treated with 1:2 trifluoroacetic acid/dichloromethane (2 mL) at room temperature for 16 h. The reaction mixture was concentrated to provide 77 mg (70%) of methyl 5-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-2-(3-guanidinopropyl)benzoate: MS (EI) m/z 759 [(M-Boc)H+]. the reaction mixture was directly poured onto silica gel purified (0 to 75% ethyl acetate/hexanes) This product was treated with 1:2 trifluoroacetic acid/dichloromethane (2 mL) at room temperature for 16 h The reaction mixture was concentrated

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

Procedure: The N′,N″-di-BOCguanidine (0.45 g, 0.60 mmol) was dissolvedin CH2Cl2 (10 mL), diluted with dry EtOH (15 mL) and the chilled solution was saturated with dry HCl. The reaction was then kept stirring at room temperature for 3 days (drying tube), when by the product started forming a precipitate over time. After evaporating the solvent to dryness, the residue was washed with ether multiple times and was dried under vacuum at 50-60° C. over night to give whitish yellow solid of the bis-guanidine dihydrochloride; mp>300° C. 1H NMR (DMSO-d6): δ 7.85 (dd, J=1.5, 8.4 Hz, 4H), 7.92 (d, J=1.2 Hz, 4H), 8.00 (dd, J=1.5, 8.4 Hz, 4H ), 9.09 (br s, 4H), 11.25 (br s, 2H). 13C NMR (DMSO-d6): δ 155.98, 138.35, 137.32, 135.00, 127.79, 127.22, 124.79. MS (ESI) m/e (rel. int.): 344 (M+, 6), 173 (100). Anal. Calc. for C20H20N6-2.0HCl-1.0H2O-0.2C2H5OH: C %, 55.11; H %, 5.71; N %, 18.90. Found C %, 55.39; H %, 5.50; N %, 18.71. (drying tube), when by the product started forming a precipitate over time After evaporating the solvent to dryness the residue was washed with ether multiple times was dried under vacuum at 50-60° C. over night