N'-benzylpropane-1,3-diamine

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

Procedure: A solution of N-(3-aminopropyl)benzylamine (38 g, 231.71 mmoles) in dry tetrahydrofuran (300 mL) was cooled to 5° C. in an ice-alcohol bath. To this cold stirred solution 2-[[(tert-butyoxycarbonyl)oxy]imino]-2-phenylacetonitrile (BOC-ON) (56.58 g, 230 mmoles) in dry tetrahydrofuran (300 mL) was added slowly during a 6 hour period. After the addition of BOC-ON, the reaction mixture was stirred at room temperature under argon for an additional 6 hours. The reaction mixture was evaporated to dryness and the residue was dissolved in ether (750 mL). The ether extract was washed with 5% sodium hydroxide solution (4×100 mL), dried over anhydrous sodium sulfate, and concentrated to dryness. The residue was purified by flash column using a chromatograpay over a silica dichloromethane→methanol gradient. The pure fractions were pooled together and evaporated to give 49.5 g (81%) of product as oil: 1H nmr (deuteriochloroform): δ1.42 (s, 9H, t-Boc), 1.65 (m, 2H, CH2CH2CH2), 2.70 (t, 2H, CH2NHCH2), 3.20 (m, 2H, BocNHCH2), 3.78 (s, 2H, ARCH2), 5.32 (br s, 1H, BocNH), 7.30 (m, 5H, ArH). The reaction mixture was evaporated to dryness the residue was dissolved in ether (750 mL) The ether extract was washed with 5% sodium hydroxide solution (4×100 mL) dried over anhydrous sodium sulfate concentrated to dryness The residue was purified by flash column evaporated

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

Procedure: Example 20 was prepared in a similar fashion to Example 18 (CZ-25) from benzaldehyde and tert-butyl(3-aminopropyl)carbamate. 1H NMR (500 MHz, D2O) δ 7.49 (quint, J=3 Hz, 5H), 4.26 (s, 2H), 3.17 (t, J=8 Hz, 2H), 3.07 (t, J=8 Hz, 2H), 2.09 (quint, J=7.5 Hz, 2H). 13C NMR (125 MHz, D2O) δ 130.6, 129.9, 129.8, 129.4, 51.4, 44.1, 36.7, 23.9. LRMS [M+H]+291.3.

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

Procedure: Example 20 was prepared in a similar fashion to Example 18 (CZ-25) from benzaldehyde and tert-butyl(3-aminopropyl)carbamate. 1H NMR (500 MHz, D2O) δ 7.49 (quint, J=3 Hz, 5H), 4.26 (s, 2H), 3.17 (t, J=8 Hz, 2H), 3.07 (t, J=8 Hz, 2H), 2.09 (quint, J=7.5 Hz, 2H). 13C NMR (125 MHz, D2O) δ 130.6, 129.9, 129.8, 129.4, 51.4, 44.1, 36.7, 23.9. LRMS [M+H]+291.3.

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

Procedure: A solution of N-(3-aminopropyl)benzylamine (38 g, 231.71 mmoles) in dry tetrahydrofuran (300 mL) was cooled to 5° C. in an ice-alcohol bath. To this cold stirred solution 2-[[(tert-butyoxycarbonyl)oxy]imino]-2-phenylacetonitrile (BOC-ON) (56.58 g, 230 mmoles) in dry tetrahydrofuran (300 mL) was added slowly during a 6 hour period. After the addition of BOC-ON, the reaction mixture was stirred at room temperature under argon for an additional 6 hours. The reaction mixture was evaporated to dryness and the residue was dissolved in ether (750 mL). The ether extract was washed with 5% sodium hydroxide solution (4×100 mL), dried over anhydrous sodium sulfate, and concentrated to dryness. The residue was purified by flash column using a chromatograpay over a silica dichloromethane→methanol gradient. The pure fractions were pooled together and evaporated to give 49.5 g (81%) of product as oil: 1H nmr (deuteriochloroform): δ 1.42 (s, 9H, t-Boc), 1.65 (m, 2H, CH2CH2CH2), 2.70 (t, 2H, CH2 NHCH2), 3.20 (m, 2H, BocNHCH2), 3.78 (s, 2H, ArCH2), 5.32 (br s, 1H, BocNH), 7.30 (m, 5H, ArH). The reaction mixture was evaporated to dryness the residue was dissolved in ether (750 mL) The ether extract was washed with 5% sodium hydroxide solution (4×100 mL) dried over anhydrous sodium sulfate concentrated to dryness The residue was purified by flash column evaporated

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

Procedure: A solution of N-(3-aminopropyl)benzylamine (38 g, 231.71 mmoles) in dry tetrahydrofuran (300 mL) was cooled to 5° C. in an ice-alcohol bath. To this cold stirred solution 2-[[(tert-butyoxycarbonyl)oxy]imino]-2-phenylacetonitrile (BOC-ON) (56.58 g, 230 mmoles) in dry tetrahydrofuran (300 mL) was added slowly during a 6 hour period. After the addition of BOC-ON, the reaction mixture was stirred at room temperature under argon for an additional 6 hours. The reaction mixture was evaporated to dryness and the residue was dissolved in ether (750 mL). The ether extract was washed with 5% sodium hydroxide solution (4×100 mL), dried over anhydrous sodium sulfate, and concentrated to dryness. The residue was purified by flash column using a chromatograpay over a silica dichloromethane→methanol gradient. The pure fractions were pooled together and evaporated to give 49.5 g (81%) of product as oil: 1H nmr (deuteriochloroform): δ 1.42 (s, 9H, t-Boc), 1.65 (m, 2H, CH2CH2CH2), 2.70 (t, 2H, CH2 NHCH2), 3.20 (m, 2H, BocNHCH2), 3.78 (s, 2H, ArCH2), 5.32 (br s, 1H, BocNH), 7.30 (m, 5H, ArH). The reaction mixture was evaporated to dryness the residue was dissolved in ether (750 mL) The ether extract was washed with 5% sodium hydroxide solution (4×100 mL) dried over anhydrous sodium sulfate concentrated to dryness The residue was purified by flash column evaporated

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

Procedure: A solution of N-(3-aminopropyl)benzylamine (38 g, 231.71 mmoles) in dry tetrahydrofuran (300 mL) was cooled to 5° C. in an ice-alcohol bath. To this cold stirred solution 2-[[(tert-butyoxycarbonyl)oxy]imino]-2-phenylacetonitrile (BOC-ON) (56.58 g, 230 mmoles) in dry tetrahydrofuran (300 mL) was added slowly during a 6 hour period. After the addition of BOC-ON, the reaction mixture was stirred at room temperature under argon for an additional 6 hours. The reaction mixture was evaporated to dryness and the residue was dissolved in ether (750 mL). The ether extract was washed with 5% sodium hydroxide solution (4×100 mL), dried over anhydrous sodium sulfate, and concentrated to dryness. The residue was purified by flash column using a chromatography over a silica dichloromethane→methanol gradient. The pure fractions were pooled together and evaporated to give 49.5 g (81%) of product as oil: 1H nmr (deuteriochloroform): δ1.42 (s, 9H, t-Boc), 1.65 (m, 2H, CH2CH2CH2), 2.70 (t, 2H, CH2NHCH2), 3.20 (m, 2H, BocNHCH2), 3.78 (s, 2H, ArCH2), 5.32 (br s, 1H, BocNH), 7.30 (m, 5H, ArH). The reaction mixture was evaporated to dryness the residue was dissolved in ether (750 mL) The ether extract was washed with 5% sodium hydroxide solution (4×100 mL) dried over anhydrous sodium sulfate concentrated to dryness The residue was purified by flash column evaporated

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

Procedure: A solution of N-(3-aminopropyl)benzylamine (38 g, 231.71 mmoles) in dry tetrahydrofuran (300 mL) was cooled to 5° C. in an ice-alcohol bath. To this cold stirred solution 2-[[(tert-butyoxycarbonyl)oxy]imino]-2-phenylacetonitrile (BOC-ON) (56.58 g, 230 mmoles) in dry tetrahydrofuran (300 mL) was added slowly during a 6 hour period. After the addition of BOC-ON, the reaction mixture was stirred at room temperature under argon for an additional 6 hours. The reaction mixture was evaporated to dryness and the residue was dissolved in ether (750 mL). The ether extract was washed with 5% sodium hydroxide solution (4×100 mL), dried over anhydrous sodium sulfate, and concentrated to dryness. The residue was purified by flash column using a chromatography over a silica dichloromethane→methanol gradient. The pure fractions were pooled together and evaporated to give 49.5 g (81%) of product as oil: 1H nmr (deuteriochloroform): δ1.42 (s, 9H, t-Boc), 1.65 (m, 2H, CH2CH2CH2), 2.70 (t, 2H, CH2NHCH2), 3.20 (m, 2H, BocNHCH2), 3.78 (s, 2H, ArCH2), 5.32 (br s, 1H, BocNH), 7.30 (m, 5H, ArH). The reaction mixture was evaporated to dryness the residue was dissolved in ether (750 mL) The ether extract was washed with 5% sodium hydroxide solution (4×100 mL) dried over anhydrous sodium sulfate concentrated to dryness The residue was purified by flash column evaporated

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

Procedure: A solution of N-(3-aminopropyl)benzylamine (38 g, 231.71 mmoles) in dry tetrahydrofuran (300 mL) was cooled to 5° C. in an ice-alcohol bath. To this cold stirred solution 2-[[(tert-butyoxycarbonyl)oxy]imino]-2-phenylacetonitrile (BOC-ON) (56.58 g, 230 mmoles) in dry tetrahydrofuran (300 mL) was added slowly during a 6 hour period. After the addition of BOC-ON, the reaction mixture was stirred at room temperature under argon for an additional 6 hours. The reaction mixture was evaporated to dryness and the residue was dissolved in ether (750 mL). The ether extract was washed with 5% sodium hydroxide solution (4×100 mL), dried over anhydrous sodium sulfate, and concentrated to dryness. The residue was purified by flash column using a chromatography over a silica dichloromethane→methanol gradient. The pure fractions were pooled together and evaporated to give 49.5 g (81%) of product as oil: 1H nmr (deuteriochloroform): δ1.42 (s, 9H, t-Boc), 1.65 (m, 2H, CH2CH2CH2), 2.70 (t, 2H, CH2NHCH2), 3.20 (m, 2H, BocNHCH2), 3.78 (s, 2H, ArCH2), 5.32 (br s, 1H, BocNH), 7.30 (m, 5H, ArH). The reaction mixture was evaporated to dryness the residue was dissolved in ether (750 mL) The ether extract was washed with 5% sodium hydroxide solution (4×100 mL) dried over anhydrous sodium sulfate concentrated to dryness The residue was purified by flash column evaporated

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

Procedure: A solution of N-(3-aminopropyl)benzylamine (38 g, 231.71 mmoles) in dry tetrahydrofuran (300 mL) was cooled to 5° C. in an ice-alcohol bath. To this cold stirred solution 2-[[(tert-butyoxycarbonyl)oxy]imino]-2-phenylacetonitrile (BOC-ON) (56.58 g, 230 mmoles) in dry tetrahydrofuran (300 mL) was added slowly during a 6 hour period. After the addition of BOC-ON, the reaction mixture was stirred at room temperature under argon for an additional 6 hours. The reaction mixture was evaporated to dryness and the residue was dissolved in ether (750 mL). The ether extract was washed with 5% sodium hydroxide solution (4×100 mL), dried over anhydrous sodium sulfate, and concentrated to dryness. The residue was purified by flash column using a chromatograpay over a silica dichloromethane→methanol gradient. The pure fractions were pooled together and evaporated to give 49.5 g (81%) of product as oil: 1H nmr (deuteriochloroform): δ 1.42 (s, 9H, t-Boc), 1.65 (m, 2H, CH2CH2CH2), 2.70 (t, 2H, CH2NHCH2), 3.20 (m, 2H, BocNHCH2), 3.78 (s, 2H, ArCH2), 5.32 (br s, 1H, BocNH), 7.30 (m, 5H, ArH). The reaction mixture was evaporated to dryness the residue was dissolved in ether (750 mL) The ether extract was washed with 5% sodium hydroxide solution (4×100 mL) dried over anhydrous sodium sulfate concentrated to dryness The residue was purified by flash column evaporated

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

Procedure: A solution of N-(3-aminopropyl)benzylamine (38 g, 231.71 mmoles) in dry tetrahydrofuran (300 mL) was cooled to 5° C. in an ice-alcohol bath. To this cold stirred solution 2-[[(tert-butyoxycarbonyl)oxy]imino]-2-phenylacetonitrile (BOC-ON) (56.58 g, 230 mmoles) in dry tetrahydrofuran (300 mL) was added slowly during a 6 hour period. After the addition of BOC-ON, the reaction mixture was stirred at room temperature under argon for an additional 6 hours. The reaction mixture was evaporated to dryness and the residue was dissolved in ether (750 mL). The ether extract was washed with 5% sodium hydroxide solution (4×100 mL), dried over anhydrous sodium sulfate, and concentrated to dryness. The residue was purified by flash column using a chromatograpay over a silica dichloromethane→methanol gradient. The pure fractions were pooled together and evaporated to give 49.5 g (81%) of product as oil: 1H nmr (deuteriochloroform): δ1.42 (s, 9H, t-Boc), 1.65 (m, 2H, CH2CH2CH2), 2.70 (t, 2H, CH2NHCH2), 3.20 (m, 2H, BocNHCH2), 3.78 (s, 2H, ARCH2), 5.32 (br s, 1H, BocNH), 7.30 (m, 5H, ArH). The reaction mixture was evaporated to dryness the residue was dissolved in ether (750 mL) The ether extract was washed with 5% sodium hydroxide solution (4×100 mL) dried over anhydrous sodium sulfate concentrated to dryness The residue was purified by flash column evaporated

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

Procedure: Example 20 was prepared in a similar fashion to Example 18 (CZ-25) from benzaldehyde and tert-butyl(3-aminopropyl)carbamate. 1H NMR (500 MHz, D2O) δ 7.49 (quint, J=3 Hz, 5H), 4.26 (s, 2H), 3.17 (t, J=8 Hz, 2H), 3.07 (t, J=8 Hz, 2H), 2.09 (quint, J=7.5 Hz, 2H). 13C NMR (125 MHz, D2O) δ 130.6, 129.9, 129.8, 129.4, 51.4, 44.1, 36.7, 23.9. LRMS [M+H]+291.3.