Reacción #476405

ord-eca54942c9ab40588a4ace807d088c59

Ecuación de reacción

O
water
CCOC(C)=O
EtOAc
C=CCCC[C@@H]1CCC[C@H]1OC(=O)N[C@H]1CCCCC/C=C\[C@@H]2C[C@@]2(C(=O)OCC)NC(=O)[C@@H]2C[C@H](OS(=O)(=O)c3ccc(Br)cc3)CN2C1=O
compound
C=CCCC[C@@H]1CCC[C@H]1OC(=O)N[C@H]1CCCCC/C=C\[C@@H]2C[C@@]2(C(=O)OCC)NC(=O)[C@@H]2C[C@H](OS(=O)(=O)c3ccc(Br)cc3)CN2C1=O
Ethyl (2S,6S,12Z,13aS,14aR,16aS)-2-{[(4-bromophenyl)sulfonyl]oxy}-5,16-dioxo-6-[({[(1R,2R)-2-pent-4-en-1-ylcyclopentyl]oxy}carbonyl)amino]-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a(5H)-carboxylate
O=C([O-])[O-].[Cs+].[Cs+]
Cs2CO3
CN1CCCC1=O
NMP
→
C=CCCC[C@@H]1CCC[C@H]1OC(=O)N[C@H]1CCCCC/C=C\[C@@H]2C[C@@]2(C(=O)OCC)NC(=O)[C@@H]2C[C@@H](Oc3cc4ccccc4nc3C=C)CN2C1=O
Ethyl (2R,6S,12Z,13aS,14aR,16aS)-5,16-dioxo-6-[({[(1R,2R)-2-pent-4-en-1-ylcyclopentyl]oxy}carbonyl)amino]-2-[(2-vinylquinolin-3-yl)oxy]-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a(5H)-carboxylate

Reactantes

O
water
CCOC(C)=O
EtOAc
C=CCCC[C@@H]1CCC[C@H]1OC(=O)N[C@H]1CCCCC/C=C\[C@@H]2C[C@@]2(C(=O)OCC)NC(=O)[C@@H]2C[C@H](OS(=O)(=O)c3ccc(Br)cc3)CN2C1=O
compound
C=CCCC[C@@H]1CCC[C@H]1OC(=O)N[C@H]1CCCCC/C=C\[C@@H]2C[C@@]2(C(=O)OCC)NC(=O)[C@@H]2C[C@H](OS(=O)(=O)c3ccc(Br)cc3)CN2C1=O
Ethyl (2S,6S,12Z,13aS,14aR,16aS)-2-{[(4-bromophenyl)sulfonyl]oxy}-5,16-dioxo-6-[({[(1R,2R)-2-pent-4-en-1-ylcyclopentyl]oxy}carbonyl)amino]-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a(5H)-carboxylate
O=C([O-])[O-].[Cs+].[Cs+]
Cs2CO3
CN1CCCC1=O
NMP

Reactivos

Ninguno

Condiciones de reacción

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

Tratamiento posterior

  1. 1
    Lavadothe organic was washed with NaHCO3 and brine
  2. 2
    Secadodried over Na2SO4
  3. 3
    Filtraciónfiltered
  4. 4
    Concentraciónconcentrated
  5. 5
    OtroThe crude material was purified by silica gel chromatography (gradient elution 5 to 80% EtOAc in hexane)

Procedimiento

To a solution of the compound from Step 3 (75 mg, 0.09 mmol) and 2-vnylquinolin-3-ol (16 mg, 0.09 mmol) in NMP (0.2 mL) was added Cs2CO3 (92 mg, 0.28 mmol). The reaction mixture was stirred at 60° C. for 1 hour. The reaction mixture was worked up with EtOAc and water, and the organic was washed with NaHCO3 and brine, dried over Na2SO4, filtered and concentrated. The crude material was purified by silica gel chromatography (gradient elution 5 to 80% EtOAc in hexane). LCMS (M+H)+=727.3.

Fuente

DOI: 10.6084/m9.figshare.5104873.v1Patente: US08377874B2uspto-grants-2013_02