Reacción #54007

ord-c8a3f1707a11479f90cdd6a6fe8a1695

Ecuación de reacción

COC(=O)NCCCCCCC(CCCC(=O)NCCCN[C@H](C(=O)OC(C)(C)C)[C@@H](O)C1O[C@@H](n2ccc(=O)n(Cc3ccc(OC)cc3)c2=O)[C@H](O[Si](C)(C)C(C)(C)C)[C@@H]1O[Si](C)(C)C(C)(C)C)C1c2ccccc2-c2ccccc21
tert-butyl (21S)-21-[(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]-11-(9H-fluoren-9-yl)-3,15-dioxo-2-oxa-4,16,20-triazadocosan-22-oate
→
COc1ccc(Cn2c(=O)ccn([C@@H]3OC([C@H](O)[C@H](NCCCNC(=O)CCCCCCCCCCN)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)-2-({3-[(11-aminoundecanoyl)amino]propyl}amino)-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]-3-hydroxypropanoate
Rendimiento 51.0%

Reactantes

COC(=O)NCCCCCCC(CCCC(=O)NCCCN[C@H](C(=O)OC(C)(C)C)[C@@H](O)C1O[C@@H](n2ccc(=O)n(Cc3ccc(OC)cc3)c2=O)[C@H](O[Si](C)(C)C(C)(C)C)[C@@H]1O[Si](C)(C)C(C)(C)C)C1c2ccccc2-c2ccccc21
tert-butyl (21S)-21-[(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]-11-(9H-fluoren-9-yl)-3,15-dioxo-2-oxa-4,16,20-triazadocosan-22-oate

Reactivos

Ninguno

Disolventes

C1CCNCC1
piperidine

Condiciones de reacción

Condiciones detalladas
See reaction.notes.procedure_details.

Tratamiento posterior

  1. 1
    OtroThe product was purified by chromatography (flash column, silica gel, 60-100% methanol in methylene chloride)

Procedimiento

By using an analogous procedure to that described for Reference Example 32, a solution of tert-butyl (21S)-21-[(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]-11-(9H-fluoren-9-yl)-3,15-dioxo-2-oxa-4,16,20-triazadocosan-22-oate (106 mg, 0.09 mmol, obtained from Example 24) in piperidine (3 ml) was stirred for 1.5 hours under nitrogen at room temperature. The product was purified by chromatography (flash column, silica gel, 60-100% methanol in methylene chloride) to provide tert-butyl (2S,3R)-2-({3-[(11-aminoundecanoyl)amino]propyl}amino)-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]-3-hydroxypropanoate (44 mg, 51%) as a white solid.

Fuente

DOI: 10.6084/m9.figshare.5104873.v1Patente: US06858591B2uspto-grants-2005_02