Potassium Carbonate → tert-butyl (2S,4 S)-2-[9-(2-{(2S)-1-[N-(methoxycarbonyl)-O-methyl-L-threonyl]pyrrolidin-2-yl}-1H-imidazol-5-yl)-1,11-dihydroisochromeno[4',3':6,7]naphtho[1,2-d]imidazol-2-yl]-4-(methoxymethyl)pyrrolidine-1-carboxylate

HRID 1509715Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1509715
[CH3:1][O:2][CH2:3][CH:4]1[CH2:8][N:7]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH:6]([C:16]2[NH:20][C:19]3[C:21]4[C:26]([CH:27]=[CH:28][C:18]=3[N:17]=2)=[CH:25][C:24]2[C:29]3[C:34]([CH2:35][O:36][C:23]=2[CH:22]=4)=[CH:33][C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][CH:30]=3)[CH2:5]1.Br[C:47]1[NH:51][C:50]([C@@H:52]2[CH2:56][CH2:55][CH2:54][N:53]2[C:57](=[O:68])[C@@H:58]([NH:63][C:64](=[O:67])[O:65][CH3:66])[C@H:59]([O:61][CH3:62])[CH3:60])=[N:49][CH:48]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:66][O:65][C:64]([NH:63][C@H:58]([C:57]([N:53]1[CH2:54][CH2:55][CH2:56][C@H:52]1[C:50]1[NH:51][C:47]([C:32]2[CH:33]=[C:34]3[CH2:35][O:36][C:23]4[CH:22]=[C:21]5[C:26]([CH:27]=[CH:28][C:18]6[N:17]=[C:16]([C@@H:6]7[CH2:5][C@H:4]([CH2:3][O:2][CH3:1])[CH2:8][N:7]7[C:9]([O:11][C:12]([CH3:13])([CH3:14])[CH3:15])=[O:10])[NH:20][C:19]=65)=[CH:25][C:24]=4[C:29]3=[CH:30][CH:31]=2)=[CH:48][N:49]=1)=[O:68])[C@@H:59]([CH3:60])[O:61][CH3:62])=[O:67]

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 86688356methyl(2S,3R)-1-((S)-2-(5-bromo-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methoxy-1-oxobutan-2-ylcarbamateHCID 178494460HCID 178494460, Verbindung

Produkt 1

HCID 178495659tert-butyl (2S,4 S)-2-[9-(2-{(2S)-1-[N-(methoxycarbonyl)-O-methyl-L-threonyl]pyrrolidin-2-yl}-1H-imidazol-5-yl)-1,11-dihydroisochromeno[4',3':6,7]naphtho[1,2-d]imidazol-2-yl]-4-(methoxymethyl)pyrrolidine-1-carboxylateAusbeute 63 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To a solution of tert-butyl 4-(methoxymethyl)-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 (1.0 g, 3.2 mmol) in a mixture of DMSO (2.0 mL) and dioxanes (2.0 mL) was added methyl (2S,3R)-1-((S)-2-(5-bromo-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methoxy-1-oxobutan-2-ylcarbamate (0.24 g, 0.62 mmol), tetrakis(triphenylphosphine)palladium (0.050 g, 0.043 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (0.030 g, 0.041 mmol), and aqueous potassium carbonate (2M, 0.65 mL, 1.3 mmol). The solution was degassed with argon for 5 min and heated, with stirring, to 85° C. for 6 h. The solution was cooled to room temperature and diluted with EtOAc. The organic layer was washed with water and brine. The aqueous layers were backextracted with EtOAc (3×). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (20% to 100% EtOAc(w/5% MeOH)/Hexanes to 60% MeOH/EtOAc) to afford tert-butyl (2S,4S)-2-[9-(2-{(2S)-1-[N-(methoxycarbonyl)-O-methyl-L-threonyl]pyrrolidin-2-yl}-1H-imidazol-5-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl]-4-(methoxymethyl)pyrrolidine-1-carboxylate (0.20 g, 63%).

Aufarbeitung

  1. customThe solution was degassed with argon for 5 min
  2. temperatureheated
  3. temperatureThe solution was cooled to room temperature
  4. additiondiluted with EtOAc
  5. washThe organic layer was washed with water and brine
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was purified by silica column chromatography (20% to 100% EtOAc(w/5% MeOH)/Hexanes to 60% MeOH/EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-709b8ee7eafc45babbbd8540608fa47e
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09221833B2

Notizen zur Reaktion

Wird geladen…