N-BOC-1,3-DIAMINO-2-PROPANOL

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

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

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

Procedure: Under argon, 0.20 g (0.50 mmol) of N2,N5-bis[(benzyloxy)carbonyl]-L-ornithine and 0.124 g (0.65 mmol) of tert-butyl(3-amino-2-hydroxypropyl)carbamate are dissolved in 6 ml of dimethylformamide. Then, at 0° C. (ice bath), 0.124 g (0.65 mmol) of EDC and 0.02 g (0.15 mmol) of HOBt are added. The mixture is slowly warmed to RT and stirred at RT for 12 h. The solution is concentrated in vacuo and the residue is taken up with ethyl acetate. The organic phase is washed successively with saturated sodium bicarbonate and sodium chloride solutions, dried over magnesium sulfate and evaporated in vacuo. The remaining solid is dried to constant weight under high vacuum. The solution is concentrated in vacuo The organic phase is washed successively with saturated sodium bicarbonate and sodium chloride solutions dried over magnesium sulfate evaporated in vacuo The remaining solid is dried to constant weight under high vacuum

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

Procedure: Under argon, 0.20 g (0.50 mmol) of N2,N5-bis[(benzyloxy)carbonyl]-L-ornithine and 0.124 g (0.65 mmol) of tert-butyl(3-amino-2-hydroxypropyl)carbamate are dissolved in 6 ml of dimethylformamide. Then, at 0° C. (ice bath), 0.124 g (0.65 mmol) of EDC and 0.02 g (0.15 mmol) of HOBt are added. The mixture is slowly warmed to RT and stirred at RT for 12 h. The solution is concentrated in vacuo and the residue is taken up with ethyl acetate. The organic phase is washed successively with saturated sodium bicarbonate and sodium chloride solutions, dried over magnesium sulfate and evaporated in vacuo. The remaining solid is dried to constant weight under high vacuum. The solution is concentrated in vacuo The organic phase is washed successively with saturated sodium bicarbonate and sodium chloride solutions dried over magnesium sulfate evaporated in vacuo The remaining solid is dried to constant weight under high vacuum

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

Procedure: Under argon, 0.30 g (0.49 mmol) of N2-[(benzyloxy)carbonyl]-N5-[[bis(tert-butoxycarbonyl)amino](imino)methyl]-L-ornithine-cyclohexanamine (1:1) and 0.12 g (0.64 mmol) of tert-butyl(3-amino-2-hydroxypropyl)carbamate are dissolved in 6 ml of dimethylformamide. Then, at 0° C. (ice bath), 0.123 g (0.64 mmol) of EDC and 0.02 g (0.15 mmol) of HOBt are added. The mixture is slowly warmed to RT and stirred at RT for 12 h. The solution is concentrated in vacuo and the residue is taken up with ethyl acetate. The organic phase is washed successively with saturated sodium bicarbonate and sodium chloride solutions, dried over magnesium sulfate and evaporated in vacuo. The remaining solid is purified by preparative HPLC (Kromasil, mobile phase acetonitrile/0.25% aqueous trifluoroacetic acid 5:95→95:5). The solution is concentrated in vacuo The organic phase is washed successively with saturated sodium bicarbonate and sodium chloride solutions dried over magnesium sulfate evaporated in vacuo The remaining solid is purified by preparative HPLC (Kromasil, mobile phase acetonitrile/0.25% aqueous trifluoroacetic acid 5:95→95:5)

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

Procedure: Under argon, 0.30 g (0.49 mmol) of N2-[(benzyloxy)carbonyl]-N5-[[bis(tert-butoxycarbonyl)amino](imino)methyl]-L-ornithine-cyclohexanamine (1:1) and 0.12 g (0.64 mmol) of tert-butyl(3-amino-2-hydroxypropyl)carbamate are dissolved in 6 ml of dimethylformamide. Then, at 0° C. (ice bath), 0.123 g (0.64 mmol) of EDC and 0.02 g (0.15 mmol) of HOBt are added. The mixture is slowly warmed to RT and stirred at RT for 12 h. The solution is concentrated in vacuo and the residue is taken up with ethyl acetate. The organic phase is washed successively with saturated sodium bicarbonate and sodium chloride solutions, dried over magnesium sulfate and evaporated in vacuo. The remaining solid is purified by preparative HPLC (Kromasil, mobile phase acetonitrile/0.25% aqueous trifluoroacetic acid 5:95→95:5). The solution is concentrated in vacuo The organic phase is washed successively with saturated sodium bicarbonate and sodium chloride solutions dried over magnesium sulfate evaporated in vacuo The remaining solid is purified by preparative HPLC (Kromasil, mobile phase acetonitrile/0.25% aqueous trifluoroacetic acid 5:95→95:5)

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

Procedure: 418.2 mg (1.1 mmol) of HATU and 258.7 mg (2 mmol) of N,N-diisopropylethylamine are added to a solution of 428.5 mg (1 mmol) of (3S)-3,7-bis{[(benzyloxy)carbonyl]amino}heptanoic acid in 30 ml of anhydrous DMF. After stirring at RT for 15 min, 209.2 mg (1.1 mmol) of tert-butyl(3-amino-2-hydroxypropyl)carbamate are added. The reaction mixture is stirred at RT for 15 h. The solvent is then evaporated and the residue is taken up in dichloromethane. The organic phase is washed with water, dried over magnesium sulfate and concentrated. The crude product is purified by preparative HPLC. The reaction mixture is stirred at RT for 15 h The solvent is then evaporated The organic phase is washed with water dried over magnesium sulfate concentrated The crude product is purified by preparative HPLC

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

Procedure: 418.2 mg (1.1 mmol) of HATU and 258.7 mg (2 mmol) of N,N-diisopropylethylamine are added to a solution of 428.5 mg (1 mmol) of (3S)-3,7-bis{[(benzyloxy)carbonyl]amino}heptanoic acid in 30 ml of anhydrous DMF. After stirring at RT for 15 min, 209.2 mg (1.1 mmol) of tert-butyl(3-amino-2-hydroxypropyl)carbamate are added. The reaction mixture is stirred at RT for 15 h. The solvent is then evaporated and the residue is taken up in dichloromethane. The organic phase is washed with water, dried over magnesium sulfate and concentrated. The crude product is purified by preparative HPLC. The reaction mixture is stirred at RT for 15 h The solvent is then evaporated The organic phase is washed with water dried over magnesium sulfate concentrated The crude product is purified by preparative HPLC

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

Procedure: 362.8 mg (0.954 mmol) of HATU and 123.3 mg (0.954 mmol) of N,N-diisopropylethylamine are added to a solution of 207.5 mg (0.867 mmol) of N-[(benzyloxy)carbonyl]-L-serine in 10 ml of anhydrous DMF. After stirring at RT for 15 min, 165 mg (0.867 mmol) of tert-butyl(3-amino-2-hydroxypropyl)carbamate are added. The reaction mixture is stirred at RT for 15 h. The solvent is then evaporated and the residue is taken up in dichloromethane. The organic phase is washed with water, dried over magnesium sulfate and concentrated. The crude product is purified by preparative HPLC. The reaction mixture is stirred at RT for 15 h The solvent is then evaporated The organic phase is washed with water dried over magnesium sulfate concentrated The crude product is purified by preparative HPLC

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

Procedure: 362.8 mg (0.954 mmol) of HATU and 123.3 mg (0.954 mmol) of N,N-diisopropylethylamine are added to a solution of 207.5 mg (0.867 mmol) of N-[(benzyloxy)carbonyl]-L-serine in 10 ml of anhydrous DMF. After stirring at RT for 15 min, 165 mg (0.867 mmol) of tert-butyl(3-amino-2-hydroxypropyl)carbamate are added. The reaction mixture is stirred at RT for 15 h. The solvent is then evaporated and the residue is taken up in dichloromethane. The organic phase is washed with water, dried over magnesium sulfate and concentrated. The crude product is purified by preparative HPLC. The reaction mixture is stirred at RT for 15 h The solvent is then evaporated The organic phase is washed with water dried over magnesium sulfate concentrated The crude product is purified by preparative HPLC

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

Procedure: 44 mg (0.12 mmol) of the compound from Example 97A and 40 mg (0.21 mmol) of tert-butyl(3-amino-2-hydroxypropyl)carbamate are dissolved in 1 ml of DMF and cooled to 0° C., and 40.3 mg (0.21 mmol) of EDC and 5.51 mg (0.04 mmol) of HOBt are successively added. The mixture is allowed to warm to room temperature and is stirred overnight. After concentration in vacuo, purification by chromatography on silica gel (dichloromethane/methanol 20:1) results in the title compound. to warm to room temperature After concentration in vacuo, purification by chromatography on silica gel (dichloromethane/methanol 20:1)

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

Procedure: 44 mg (0.12 mmol) of the compound from Example 97A and 40 mg (0.21 mmol) of tert-butyl(3-amino-2-hydroxypropyl)carbamate are dissolved in 1 ml of DMF and cooled to 0° C., and 40.3 mg (0.21 mmol) of EDC and 5.51 mg (0.04 mmol) of HOBt are successively added. The mixture is allowed to warm to room temperature and is stirred overnight. After concentration in vacuo, purification by chromatography on silica gel (dichloromethane/methanol 20:1) results in the title compound. to warm to room temperature After concentration in vacuo, purification by chromatography on silica gel (dichloromethane/methanol 20:1)