2-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]amino]acetic acid

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

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: III (6.0 g, 0.0148 mole) (39) was deblocked with HCl/Dioxane and solvent removed under reduced pressure. The residue was triturated with ether, filtered, washed with ether, then pet. ether and dried. A very hygroscopic material was obtained (4.2 g, 0.0123 mole) which was coupled in DMF with II (2.86 g, 0.0123 mole) in the presence of 10% excess of EDCI (2.60 g) and HOBt (2.07 g). The reaction was worked up as described for I to obtain IV as a white foam in a quantitative yield, no sharp m.p. 54°-62° C. Rf2, 0.42; Rf3, 0.74. Anal. Calcd. for C26H38N4O7 ; C, 60.21; H, 7.38; N, 10.80%. Found: C, 60.0; H, 7.46; N, 10.81%. removed under reduced pressure The residue was triturated with ether filtered washed with ether pet. ether and dried A very hygroscopic material was obtained (4.2 g, 0.0123 mole) which

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

Procedure: from N-(2-L-leucyl-amino-2-deoxy-β-D-glucopyranosyl)-N-tetradecyl-oleamide and N-tert-butyloxycarbonyl-glycyl-glycine. Yield 92%. [α]D =+4.2° (c=0.83, tetrahydrofuran).

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

Procedure: IV (6.2 g, 0.012 mole) in acetic acid was hydrogenated and worked up as for II to obtain V quantitatively, no sharp m.p. 743 Calcd. for 83° C. Rf3, 0.25; Rf4, 0.15. Anal. Calcd. for C19H32N4O7 : C, 51.10; H, 7.67; N, 12.54%. Found: C, 51.28: H, 7.50, N, 12.38%. to obtain V quantitatively for 83° C

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

Procedure: IV (6.2 g, 0.012 mole) in acetic acid was hydrogenated and worked up as for II to obtain V quantitatively, no sharp m.p. 743 Calcd. for 83° C. Rf3, 0.25; Rf4, 0.15. Anal. Calcd. for C19H32N4O7 : C, 51.10; H, 7.67; N, 12.54%. Found: C, 51.28: H, 7.50, N, 12.38%. to obtain V quantitatively for 83° C

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

Procedure: III (6.0 g, 0.0148 mole) was deblocked with HCl/Dioxane and solvent removed under reduced pressure. The residue was triturated with ether, filtered, washed with ether, then pet. ether and dried. A very hygroscopic material was obtained (4.2 g, 0.0123 mole) which was coupled in DMF with II (2.86 g, 0.0123 mole) in the presence of 10% excess of EDCI (2.60 g) and HOBt (2.07 g). The reaction was worked up as described for I to obtain IV as a white foam in a quantitative yield, no sharp m.p. 54°-62° C. Rf2, 0.42, Rf3, 0.74. Anal Calcd. for C26H38N4)7 ; C, 60.21; H, 7.38; N, 10.805. Found: C, 60.0; H, 7.46; N, 10.81%. removed under reduced pressure The residue was triturated with ether filtered washed with ether pet. ether and dried A very hygroscopic material was obtained (4.2 g, 0.0123 mole) which

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

Procedure: To N-Boc-glycylglycine (696 mg, 3.00 mmol, 1.00 equiv) in THF (10.0 mL) at 0° C. was added EDCI (1.15 g, 6.00 mmol, 2.00 equiv), HOBt (810 mg, 6.00 mmol, 2.00 equiv), n,n-diisopropylethyl amine (1.56 mL, 9.00 mmol, 3.00 equiv) and 4-(Dimethylamino)pyridine (36 mg, 0.030 mmol, 0.10 equiv) and L-phenylalanine methyl ester (647 mg, 3.00 mmol, 1.00 equiv). The reaction mixture was stirred for 1 hr at 0° C. and stirred for 12 h at room temperature. The reaction mixture was diluted with ethyl acetate and washed with water and dried (Na2SO4). The filtrate is concentrated in vacuo and the residue is purified by chromatography on silica gel eluting with DCM/MeOH 10:1 (v/v) to afford 1.10 g of the title compound as a colorless oil (93% yield). stirred for 12 h at room temperature washed with water dried (Na2SO4) The filtrate is concentrated in vacuo the residue is purified by chromatography on silica gel eluting with DCM/MeOH 10:1 (v/v)

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

Procedure: 4.43 g of Boc-Gly-Gly-OH, A (2) is dissolved in 30 ml DMF and cooled to 0° C., after which 1 equivalent TEA (triethylamine) is added. The mixture is cooled further to about -10° C., after which 1 equivalent (eq) ethyl chloroformate is added and the whole is stirred for about 10 minutes. 6.6 g H-Phe-Met-OMe.HCl (A.1) in 30 ml DMF and 1.1 eq TEA is then added to the mixture, which is stirred for about 30 minutes at about -10° C. and for a further 20 hours at room temperature. After cooling to about -10° C., TEA.HCl is separated by filtration and the filtrate is evaporated to dryness. The residue is dissolved in 235 ml EtOAc and 55 ml water and is subsequently washed with 30% NaCl solution, 0.1 N HCl, 30% NaCl solution, 5% NaHCO3 solution and 30% NaCl solution. The solution is then dried over Na2SO4 filtered and evaporated to dryness. Melting point 100°-101° C.; Rf in CHCl3 :CH3OH:Wa (70:30:5)=0.94 on SiO2. The mixture is cooled further to about -10° C. is stirred for about 30 minutes at about -10° C. and for a further 20 hours at room temperature After cooling to about -10° C. HCl is separated by filtration the filtrate is evaporated to dryness The residue is dissolved in 235 ml EtOAc 55 ml water and is subsequently washed with 30% NaCl solution, 0.1 N HCl, 30% NaCl solution, 5% NaHCO3 solution and 30% NaCl solution The solution is then dried over Na2SO4 filtered evaporated to dryness

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

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

Procedure: 4.43 g of Boc-Gly-Gly-OH, A (2) is dissolved in 30 ml DMF and cooled to 0° C., after which 1 equivalent TEA (triethylamine) is added. The mixture is cooled further to about -10° C., after which 1 equivalent (eq) ethyl chloroformate is added and the whole is stirred for about 10 minutes. 6.6 g H-Phe-Met-OMe.HCl (A.1) in 30 ml DMF and 1.1 eq TEA is then added to the mixture, which is stirred for about 30 minutes at about -10° C. and for a further 20 hours at room temperature. After cooling to about -10° C., TEA.HCl is separated by filtration and the filtrate is evaporated to dryness. The residue is dissolved in 235 ml EtOAc and 55 ml water and is subsequently washed with 30% NaCl solution, 0.1 N HCl, 30% NaCl solution, 5% NaHCO3 solution and 30% NaCl solution. The solution is then dried over Na2SO4 filtered and evaporated to dryness. Melting point 100°-101° C.; Rf in CHCl3 :CH3OH:Wa (70:30:5)=0.94 on SiO2. The mixture is cooled further to about -10° C. is stirred for about 30 minutes at about -10° C. and for a further 20 hours at room temperature After cooling to about -10° C. HCl is separated by filtration the filtrate is evaporated to dryness The residue is dissolved in 235 ml EtOAc 55 ml water and is subsequently washed with 30% NaCl solution, 0.1 N HCl, 30% NaCl solution, 5% NaHCO3 solution and 30% NaCl solution The solution is then dried over Na2SO4 filtered evaporated to dryness