Reaktion #54002

ord-ea92cbac36194f8fa157da3da52a3cfe

Reaktionsgleichung

COc1ccc(Cn2c(=O)ccn([C@@H]3OC([C@H](O)[C@H](NCCCNC(=O)[C@H](CCCCNC(=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 (9S,16S)-9-{[(benzyloxy)carbonyl]amino}
COc1ccc(Cn2c(=O)ccn([C@@H]3OC([C@H](O)[C@H](NCCCNC(=O)[C@H](CCCCNC(=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 (9S,16S)-9-{[(benzyloxy)carbonyl]amino}-16-[(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]-3,10-dioxo-1-phenyl-2-oxa-4,11,15-triazaheptadecan-17-oate
→
COc1ccc(Cn2c(=O)ccn([C@@H]3OC([C@H](O)[C@H](NCCCNC(=O)[C@@H](N)CCCCN)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 (2S,3R)-3-[(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]-2-[(3-{[(2S)-2,6-diaminohexanoyl]amino}propyl) amino]-3-hydroxypropanoate
Ausbeute 92.0%

Edukte

COc1ccc(Cn2c(=O)ccn([C@@H]3OC([C@H](O)[C@H](NCCCNC(=O)[C@H](CCCCNC(=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 (9S,16S)-9-{[(benzyloxy)carbonyl]amino}
COc1ccc(Cn2c(=O)ccn([C@@H]3OC([C@H](O)[C@H](NCCCNC(=O)[C@H](CCCCNC(=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 (9S,16S)-9-{[(benzyloxy)carbonyl]amino}-16-[(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]-3,10-dioxo-1-phenyl-2-oxa-4,11,15-triazaheptadecan-17-oate

Reagenzien

[Pd]
palladium on carbon

Lösungsmittel

CO
methanol

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Vorschrift

By using an analogous procedure to that described for Example 2, tert-butyl (9S,16S)-9-{[(benzyloxy)carbonyl]amino}-16-[(R)-[(3R,4R,5R)-3,4-bis{[tert-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-3,10-dioxo-1-phenyl-2-oxa-4,11,15-triazaheptadecan-17-oate (70 mg, 0.06 mmol, obtained from Example 18) was hydrogenated in methanol (2 ml) using 10% palladium on carbon (17 mg) to provide tert-butyl (2S,3R)-3-[(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]-2-[(3-{[(2S)-2,6-diaminohexanoyl]amino}propyl) amino]-3-hydroxypropanoate (50 mg, 92%) as a white solid.

Quelle

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