Potassium Carbonate → HCID 178502450, Verbindung

Temperatur

95 °C

(2S,4S)-tert-butyl 4-methyl-2-[9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate (558 mg, 0.96 mmol), methyl (S)-1-((2S,4S)-2-(5-iodo-1H-imidazol-2-yl)-4-methylpyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (501 mg, 1.15 mmol), Pd(PPh3)4 (111 mg, 0.096 mmol), PdCl2(dppf)2 (70 mg, 0.096 mmol), and K2CO3 (2M in H2O, 1.6 mL, 3.17 mmol.) were combined in DMSO (6 mL) and dioxane (6 mL). The mixture was degassed with bubbling N2 for 10 min then heated to 95° C. for 14 h. After cooling, the reaction mixture was diluted with EtOAc, and washed successively with saturated aqueous NaHCO3 and brine. The organics were dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (0%-30% MeOH/EtOAc) to afford tert-butyl (2S,4S)-2-[9-(2-{(2S,4S)-1-[N-(methoxycarbonyl)-L-valyl]-4-methylpyrrolidin-2-yl}-1H-imidazol-5-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl]-4-methylpyrrolidine-1-carboxylate (257 mg, 35%).

1. customThe mixture was degassed with bubbling N2 for 10 min
2. temperatureAfter cooling
3. additionthe reaction mixture was diluted with EtOAc
4. washwashed successively with saturated aqueous NaHCO3 and brine
5. dry with materialThe organics were dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe crude residue was purified by silica column chromatography (0%-30% MeOH/EtOAc)

ORD-Eintrag

ord-5d7f08627b7b413db1b4aa401d1a898a

Quelldatensatz

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08940718B2