Reacción #172893

ord-051becbae45c414caf8a2ccb979a8349

Ecuación de reacción

C=C(C)[C@@H]1CC[C@]2(NCCN3CCS(=O)(=O)CC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O[C@H]7O[C@H](C(=O)OCc8ccccc8)[C@@H](O)[C@H](O)[C@H]7O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
(2S,3S,4S,5R,6R)-benzyl 6-((4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate
C[SiH](C)C(C)(C)C
tert-butyldimethylsilane
CCN(CC)CC
triethylamine
CCCC[N+](CCCC)(CCCC)CCCC.[F-]
TBAF
→
C=C(C)[C@@H]1CC[C@]2(NCCN3CCS(=O)(=O)CC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O[C@H]7O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]7O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
desired product
Rendimiento 52.0%
C=C(C)[C@@H]1CC[C@]2(NCCN3CCS(=O)(=O)CC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O[C@H]7O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]7O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
(2S,3S,4S,5R,6R)-6-((4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid
Rendimiento 52.0%

Reactantes

C=C(C)[C@@H]1CC[C@]2(NCCN3CCS(=O)(=O)CC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O[C@H]7O[C@H](C(=O)OCc8ccccc8)[C@@H](O)[C@H](O)[C@H]7O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
(2S,3S,4S,5R,6R)-benzyl 6-((4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate
C[SiH](C)C(C)(C)C
tert-butyldimethylsilane
CCN(CC)CC
triethylamine
CCCC[N+](CCCC)(CCCC)CCCC.[F-]
TBAF

Reactivos

CC(=O)[O-].CC(=O)[O-].[Pd+2]
palladium acetate

Disolventes

CC(Cl)Cl
dichloroethane
C1CCOC1
THF

Condiciones de reacción

Temperatura
60°CELSIUS
Condiciones detalladas
See reaction.notes.procedure_details.

Tratamiento posterior

  1. 1
    TemperaturaThe reaction mixture was cooled to room temperature
  2. 2
    Filtraciónfiltered
  3. 3
    Concentraciónthe filtrates were concentrated
  4. 4
    Otroto provide the residue
  5. 5
    OtroThe reaction mixture was then purified by prep

Procedimiento

A mixture of (2S,3S,4S,5R,6R)-benzyl 6-((4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate (8 mg, 8.36 mmol), tert-butyldimethylsilane (1.943 mg, 0.017 mmol), palladium acetate (3.75 mg, 0.017 mmol) and triethylamine (5.82 μl, 0.042 mmol) in dichloroethane (1 mL) was heated up at 60° C. for 2 hours. The reaction mixture was cooled to room temperature, filtered and the filtrates were concentrated to provide the residue. To this residue in THF (1.0 mL) was added TBAF (10.93 mg, 0.042 mmol), the reaction mixture was stirred for 1 hours. The reaction mixture was then purified by prep. HPLC to provide the desired product as a colorless oil (4 mg, 52%). LCMS: m/e 867.69 (M+H)+, 2.42 min (method 10). 1H NMR (500 MHz, Acetic) δ 8.06 (d, J=8.2 Hz, 2H), 7.31 (d, J=8.2 Hz, 2H), 5.96 (d, J=7.9 Hz, 1H), 5.37 (d, J=4.4 Hz, 1H), 4.84 (s, 1H), 4.74 (s, 1H), 4.40-4.16 (m, 1H), 4.02-3.76 (m, 3H), 3.46 (d, J=12.3 Hz, 1H), 3.37-3.22 (m, 6H), 3.20-3.11 (m, 3H), 3.07 (br. s., 2H), 3.00-2.82 (m, 1H), 2.37-1.03 (m, 22H), 1.76 (s, 3H), 1.29 (s, 3H), 1.14 (s, 3H), 1.10 (s, 3H), 1.02 (s, 3H), 0.99 (s, 3H).

Fuente

DOI: 10.6084/m9.figshare.5104873.v1Patente: US08846647B2uspto-grants-2014_09