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

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A solution of anhydrous methanol (0.04 ml, 1.0 mmol), N-,N′-,N″-tri-Boc-guanidine (1.80 g, 5.0 mmol), and triphenylphoshine (393 mg, 1.5 mmol) in anhydrous THF (50 ml) is cooled to −5° C. under an atmosphere of argon. Diethylazodicarboxylate (DEAD, 0.22 ml, 1.5 mmol) is added dropwise at a rate such that the reaction mixture is completely colorless before addition of the next drop. After the addition is completed, the reaction mixture is refluxed for 15 h. The solution is then cooled to room temperature, and hexanes (50 ml) is added. A precipitate of excess N-,N′-,N″-tri-Boc-guanidine forms which is collected by filtration on a Buechner-funnel and washed with a mixture of THF/hexanes 1:1. The filtrate is concentrated under reduced pressure and the product (colorless oil, 182 mg, 49%) isolated by flash chromatography on silica gel (eluent: dichloromethane-ethyl ether 98:2): 1H NMR (360 MHz, DMSO-d6) δ 10.17 (s, 1H), 2.94 (s, 3H), 1.43-1.36 (27H); FAB-MS m/e (relative intensity). is completely colorless before addition of the next drop After the addition the reaction mixture is refluxed for 15 h A precipitate of excess N-,N′-,N″-tri-Boc-guanidine forms which is collected by filtration on a Buechner-funnel washed with a mixture of THF/hexanes 1:1 The filtrate is concentrated under reduced pressure the product (colorless oil, 182 mg, 49%) isolated by flash chromatography on silica gel (eluent: dichloromethane-ethyl ether 98:2)

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a 100 mL, 3-neck, round bottom flask were added 3-(1-methyl -piperidin-4-yl)-propan-1-ol (1.91 g, 0.012 mol), Polymer Labs (Varian) PL-TPP resin (9.83 g, 0.014 mol), N,N′,N″-tri-Boc-guanidine (4.36 g, 0.012 mol) and THF (anhydrous, 100 mL). The resultant mixture was stirred and cooled to 2° C., at which time DEAD (2.53 g, 0.014 mol) was added drop wise over 10 min. Upon completion of addition, the flask was warmed to room temperature, aged for 4 h and filtered to remove the resin bound oxide. The resultant cake was rinsed with THF (25 mL) and heptane (2×25 mL). The filtrates were combined, extracted with saturated aqueous NaHCO3 (2×25 mL), dried over anhydrous MgSO4, filtered and concentrated. The resultant residue was triturated in hot ethanol (25 mL), cooled to room temperature and filtered. The filtrate was concentrated to yield N-[3-(1-methylpiperidin-4-yl)-propyl]-N,N′,N″-tri-Boc-guanidine. was added drop wise over 10 min Upon completion of addition filtered to remove the resin The resultant cake was rinsed with THF (25 mL) and heptane (2×25 mL) extracted with saturated aqueous NaHCO3 (2×25 mL) dried over anhydrous MgSO4 filtered concentrated The resultant residue was triturated in hot ethanol (25 mL) cooled to room temperature filtered The filtrate was concentrated

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

Procedure: To a 100 mL, 3-neck, round bottom flask were added 3-(1-methyl-piperidin-4-yl)-propan-1-ol (1.91 g, 0.012 mol), Polymer Labs (Varian) PL-TPP resin (9.83 g, 0.014 mol), N,N′,N″-tri-Boc-guanidine (4.36 g, 0.012 mol) and THF (anhydrous, 100 mL). The resultant mixture was stirred and cooled to 2° C., at which time DEAD (2.53 g, 0.014 mol) was added drop wise over 10 min. Upon completion of addition, the flask was warmed to room temperature, aged for 4 h and filtered to remove the resin bound oxide. The resultant cake was rinsed with THF (25 mL) and heptane (2×25 mL). The filtrates were combined, extracted with saturated aqueous NaHCO3 (2×25 mL), dried over anhydrous MgSO4, filtered and concentrated. The resultant residue was triturated in hot ethanol (25 mL), cooled to room temperature and filtered. The filtrate was concentrated to yield N-[3-(1-methylpiperidin-4-yl)-propyl]-N,N′,N″-tri-Boc-guanidine. was added drop wise over 10 min Upon completion of addition filtered to remove the resin The resultant cake was rinsed with THF (25 mL) and heptane (2×25 mL) extracted with saturated aqueous NaHCO3 (2×25 mL) dried over anhydrous MgSO4 filtered concentrated The resultant residue was triturated in hot ethanol (25 mL) cooled to room temperature filtered The filtrate was concentrated

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

Procedure: To a 100 mL, 3-neck, round bottom flask were added 3-(1-methyl-piperidin-4-yl)-propan-1-ol (1.91 g, 0.012 mol), Polymer Labs (Varian) PL-TPP resin (9.83 g, 0.014 mol), N,N′,N″-tri-Boc-guanidine (4.36 g, 0.012 mol) and THF (anhydrous, 100 mL). The resultant mixture was stirred and cooled to 2° C., at which time DEAD (2.53 g, 0.014 mol) was added drop wise over 10 min. Upon completion of addition, the flask was warmed to room temperature, aged for 4 h and filtered to remove the resin bound oxide. The resultant cake was rinsed with THF (25 mL) and heptane (2×25 mL). The filtrates were combined, extracted with saturated aqueous NaHCO3 (2×25 mL), dried over anhydrous MgSO4, filtered and concentrated. The resultant residue was triturated in hot ethanol (25 mL), cooled to room temperature and filtered. The filtrate was concentrated to yield N-[3-(1-methylpiperidin-4-yl)-propyl]-N,N′,N″-tri-Boc-guanidine. was added drop wise over 10 min Upon completion of addition filtered to remove the resin The resultant cake was rinsed with THF (25 mL) and heptane (2×25 mL) extracted with saturated aqueous NaHCO3 (2×25 mL) dried over anhydrous MgSO4 filtered concentrated The resultant residue was triturated in hot ethanol (25 mL) cooled to room temperature filtered The filtrate was concentrated

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

Procedure: To a 100 mL, 3-neck, round bottom flask were added 3-(1-methyl-piperidin-4-yl)-propan-1-ol (1.91 g, 0.012 mol), Polymer Labs (Varian) PL-TPP resin (9.83 g, 0.014 mol), N,N′,N″-tri-Boc-guanidine (4.36 g, 0.012 mol) and THF (anhydrous, 100 mL). The resultant mixture was stirred and cooled to 2° C., at which time DEAD (2.53 g, 0.014 mol) was added drop wise over 10 min. Upon completion of addition, the flask was warmed to room temperature, aged for 4 h and filtered to remove the resin bound oxide. The resultant cake was rinsed with THF (25 mL) and heptane (2×25 mL). The filtrates were combined, extracted with saturated aqueous NaHCO3 (2×25 mL), dried over anhydrous MgSO4, filtered and concentrated. The resultant residue was triturated in hot ethanol (25 mL), cooled to room temperature and filtered. The filtrate was concentrated to yield N-[3-(1-methylpiperidin-4-yl)-propyl]-N,N′,N″-tri-Boc-guanidine. was added drop wise over 10 min Upon completion of addition filtered to remove the resin The resultant cake was rinsed with THF (25 mL) and heptane (2×25 mL) extracted with saturated aqueous NaHCO3 (2×25 mL) dried over anhydrous MgSO4 filtered concentrated The resultant residue was triturated in hot ethanol (25 mL) cooled to room temperature filtered The filtrate was concentrated

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

Procedure: To a 100 mL, 3-neck, round bottom flask were added 3-(1-methyl-piperidin-4-yl)-propan-1-ol (1.91 g, 0.012 mol), Polymer Labs (Varian) PL-TPP resin (9.83 g, 0.014 mol), N,N′,N″-tri-Boc-guanidine (4.36 g, 0.012 mol) and THF (anhydrous, 100 mL). The resultant mixture was stirred and cooled to 2° C., at which time DEAD (2.53 g, 0.014 mol) was added drop wise over 10 min. Upon completion of addition, the flask was warmed to room temperature, aged for 4 h and filtered to remove the resin bound oxide. The resultant cake was rinsed with THF (25 mL) and heptane (2×25 mL). The filtrates were combined, extracted with saturated aqueous NaHCO3 (2×25 mL), dried over anhydrous MgSO4, filtered and concentrated. The resultant residue was triturated in hot ethanol (25 mL), cooled to room temperature and filtered. The filtrate was concentrated to yield N-[3-(1-methylpiperidin-4-yl)-propyl]-N,N′,N″-tri-Boc-guanidine. was added drop wise over 10 min Upon completion of addition filtered to remove the resin The resultant cake was rinsed with THF (25 mL) and heptane (2×25 mL) extracted with saturated aqueous NaHCO3 (2×25 mL) dried over anhydrous MgSO4 filtered concentrated The resultant residue was triturated in hot ethanol (25 mL) cooled to room temperature filtered The filtrate was concentrated

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

Procedure: To a 100 mL, 3-neck, round bottom flask were added 3-(1-methyl-piperidin-4-yl)-propan-1-ol (1.91 g, 0.012 mol), Polymer Labs (Varian) PL-TPP resin (9.83 g, 0.014 mol), N,N′,N″-tri-Boc-guanidine (4.36 g, 0.012 mol) and THF (anhydrous, 100 mL). The resultant mixture was stirred and cooled to 2° C., at which time DEAD (2.53 g, 0.014 mol) was added drop wise over 10 min. Upon completion of addition, the flask was warmed to room temperature, aged for 4 h and filtered to remove the resin bound oxide. The resultant cake was rinsed with THF (25 mL) and heptane (2×25 mL). The filtrates were combined, extracted with saturated aqueous NaHCO3 (2×25 mL), dried over anhydrous MgSO4, filtered and concentrated. The resultant residue was triturated in hot ethanol (25 mL), cooled to room temperature and filtered. The filtrate was concentrated to yield N-[3-(1-methylpiperidin-4-yl)-propyl]-N,N′,N″-tri-Boc-guanidine. was added drop wise over 10 min Upon completion of addition filtered to remove the resin The resultant cake was rinsed with THF (25 mL) and heptane (2×25 mL) extracted with saturated aqueous NaHCO3 (2×25 mL) dried over anhydrous MgSO4 filtered concentrated The resultant residue was triturated in hot ethanol (25 mL) cooled to room temperature filtered The filtrate was concentrated

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

Procedure: A solution of anhydrous methanol (0.04 ml, 1.0 mmol), N-,N'-,N"-tri-Boc-guanidine (1.80 g, 5.0 mmol), and triphenylphoshine (393 mg, 1.5 mmol) in anhydrous THF (50 ml) is cooled to -5° C. under an atmosphere of argon. Diethylazodicarboxylate (DEAD, 0.22 ml, 1.5 mmol) is added dropwise at a rate such that the reaction mixture is completely colorless before addition of the next drop. After the addition is completed, the reaction mixture is refluxed for 15 h. The solution is then cooled to room temperature, and hexanes (50 ml) is added. A precipitate of excess N-,N'-,N"-tri-Boc-guanidine forms which is collected by filtration on a Buechner-funnel and washed with a mixture of THF/hexanes 1:1. The filtrate is concentrated under reduced pressure and the product (colorless oil, 182 mg, 49%) isolated by flash chromatography on silica gel (eluent: dichloromethane-ethyl ether 98:2): 1H NMR (360 MHz, DMSO-d6) δ 10.17 (s, 1H), 2.94 (s, 3H), 1.43-1.36 (27H); FAB-MS m/e (relative intensity) 396 (100, M+Na+)0.374 (91, M+H+). is completely colorless before addition of the next drop After the addition the reaction mixture is refluxed for 15 h A precipitate of excess N-,N'-,N"-tri-Boc-guanidine forms which is collected by filtration on a Buechner-funnel washed with a mixture of THF/hexanes 1:1 The filtrate is concentrated under reduced pressure the product (colorless oil, 182 mg, 49%) isolated by flash chromatography on silica gel (eluent: dichloromethane-ethyl ether 98:2)

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

Procedure: A solution of anhydrous methanol (0.04 ml, 1.0 mmol), N-,N′-,N″-tri-Boc-guanidine (1.80 g, 5.0 mmol), and triphenylphoshine (393 mg, 1.5 mmol) in anhydrous THF (50 ml) is cooled to −5° C. under an atmosphere of argon. Diethylazodicarboxylate (DEAD, 0.22 ml, 1.5 mmol) is added dropwise at a rate such that the reaction mixture is completely colorless before addition of the next drop. After the addition is completed, the reaction mixture is refluxed for 15 h. The solution is then cooled to room temperature, and hexanes (50 ml) is added. A precipitate of excess N-,N′-,N″-tri-Boc-guanidine forms which is collected by filtration on a Buechner-funnel and washed with a mixture of THF/hexanes 1:1. The filtrate is concentrated under reduced pressure and the product (colorless oil, 182 mg, 49%) isolated by flash chromatography on silica gel (eluent: dichloromethane-ethyl ether 98:2): 1H NMR (360 MHz, DMSO-d6) δ 10.17 (s, 1H), 2.94 (s, 3H), 1.43-1.36 (27H); FAB-MS m/e (relative intensity). is completely colorless before addition of the next drop After the addition the reaction mixture is refluxed for 15 h A precipitate of excess N-,N′-,N″-tri-Boc-guanidine forms which is collected by filtration on a Buechner-funnel washed with a mixture of THF/hexanes 1:1 The filtrate is concentrated under reduced pressure the product (colorless oil, 182 mg, 49%) isolated by flash chromatography on silica gel (eluent: dichloromethane-ethyl ether 98:2)