Reaction #54001

ord-0d67aaf0d26f4161afac6462400413c4

Reaction equation

COc1ccc(Cn2c(=O)ccn([C@@H]3OC([C@H](O)[C@H](NCCCNC(=O)[C@H](CC(=O)OCc4ccccc4)NC(=O)OCc4ccccc4)C(=O)OC(C)(C)C)[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]3O[Si](C)(C)C(C)(C)C)c2=O)cc1
tert-butyl (5S,12S)-5-[2-(benzyloxy)-2-oxoethyl]-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate
→
COc1ccc(Cn2c(=O)ccn([C@@H]3OC([C@@H](O)[C@H](NCCCNC(=O)[C@@H](N)CC(=O)O)C(=O)OC(C)(C)C)[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]3O[Si](C)(C)C(C)(C)C)c2=O)cc1
(3S)-3-amino-4-[(3-{[(1S,2S)-2-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-1-(tert-butoxycarbonyl)-2-hydroxyethyl]amino}propyl)amino]-4-oxobutanoic acid
Yield 99.4%

Reactants

COc1ccc(Cn2c(=O)ccn([C@@H]3OC([C@H](O)[C@H](NCCCNC(=O)[C@H](CC(=O)OCc4ccccc4)NC(=O)OCc4ccccc4)C(=O)OC(C)(C)C)[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]3O[Si](C)(C)C(C)(C)C)c2=O)cc1
tert-butyl (5S,12S)-5-[2-(benzyloxy)-2-oxoethyl]-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate

Reagents

[Pd]
palladium on carbon

Solvents

CO
methanol

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Procedure

By using an analogous procedure to that described for Example 2, tert-butyl (5S,12S)-5-[2-(benzyloxy)-2-oxoethyl]-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate (20 mg, 0.018 mmol, obtained from Example 16) was hydrogenated in methanol (1.5 ml) using 10% palladium on carbon (10 mg) to provide (3S)-3-amino-4-[(3-{[(1S,2S)-2-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-1-(tert-butoxycarbonyl)-2-hydroxyethyl]amino}propyl)amino]-4-oxobutanoic acid (16 mg, 99%) as a white solid.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US06858591B2uspto-grants-2005_02