Potassium Carbonate → HCID 178502339, Verbindung

HRID 1751673Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1751673
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:31](=[CH:32][CH:33]=2)[C:15]2[NH:16][C:17]([C@@H:19]4[CH2:23][CH2:22][CH2:21][N:20]4[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[N:18][C:14]=2[CH:13]=[CH:12]3)O1.Br[C:36]1[C:37]([F:65])=[C:38]2[C:62](=[CH:63][CH:64]=1)[C:42]1[NH:43][C:44]([C@@H:46]3[CH2:50][CH2:49][CH2:48][N:47]3[C:51](=[O:61])[C@@H:52]([NH:56][C:57](=[O:60])[O:58][CH3:59])[CH:53]([CH3:55])[CH3:54])=[N:45][C:41]=1[CH:40]=[CH:39]2.C([O-])([O-])=O.[K+].[K+]>COCCOC.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]>[F:65][C:37]1[C:36]([C:9]2[CH:10]=[C:11]3[C:31](=[CH:32][CH:33]=2)[C:15]2[NH:16][C:17]([C@@H:19]4[CH2:23][CH2:22][CH2:21][N:20]4[C:24]([O:26][C:27]([CH3:29])([CH3:30])[CH3:28])=[O:25])=[N:18][C:14]=2[CH:13]=[CH:12]3)=[CH:64][CH:63]=[C:62]2[C:38]=1[CH:39]=[CH:40][C:41]1[N:45]=[C:44]([C@@H:46]3[CH2:50][CH2:49][CH2:48][N:47]3[C:51](=[O:61])[C@@H:52]([NH:56][C:57]([O:58][CH3:59])=[O:60])[CH:53]([CH3:54])[CH3:55])[NH:43][C:42]=12

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 178451892HCID 178451892, VerbindungHCID 178502338HCID 178502338, Verbindung

Produkt 1

HCID 178502339HCID 178502339, VerbindungAusbeute 71,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

(S)-tert-butyl 2-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate (250 mg, 0.48 mmol) and methyl (S)-1-((S)-2-(7-bromo-6-fluoro-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (200 mg, 0.4 mmol), Pd(PPh3)4 (46 mg, 0.04 mmol), Pd(dppf)2Cl2 (29 mg, 0.04 mmol), and K2CO3 (2M in H2O, 0.67 mL, 1.34 mmoL) were combined in DME (6 mL). The mixture was degassed with bubbling N2 for 10 min the heated to 85° C. for 16 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% to 30% MeOH/EtOAc) to afford (S)-tert-butyl 2-(6′-fluoro-2′-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H,1′H-7,7′-binaphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate (213 mg, 71%).

Aufarbeitung

  1. customThe mixture was degassed with bubbling N2 for 10 min the
  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% to 30% MeOH/EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-98683e761a8e4a6cb4197c039ec3a6d8
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09156823B2

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