Potassium Carbonate → HCID 178502330, Verbindung

HRID 1751439Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1751439
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]([CH:13]3[C@@H:18]4[CH2:19][C@@H:15]([CH2:16][CH2:17]4)[N:14]3[C:20](=[O:31])[C@@H:21]([NH:26][C:27](=[O:30])[O:28][CH3:29])[C@H:22]([O:24][CH3:25])[CH3:23])=[N:10][CH:9]=2)=[C:4]([F:32])[CH:3]=1.[CH3:33][CH:34]([CH3:70])[C@H:35]([NH:65][C:66](=[O:69])[O:67][CH3:68])[C:36](=[O:64])[N:37]1[CH2:41][CH2:40][CH2:39][C@H:38]1[C:42]1[NH:46][C:45]2[C:47]3[C:52]([CH:53]=[CH:54][C:44]=2[N:43]=1)=[CH:51][C:50](B1OC(C)(C)C(C)(C)O1)=[CH:49][CH:48]=3.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>[CH3:68][O:67][C:66]([NH:65][C@@H:35]([CH:34]([CH3:70])[CH3:33])[C:36]([N:37]1[CH2:41][CH2:40][CH2:39][C@H:38]1[C:42]1[NH:46][C:45]2[C:47]3[C:52]([CH:53]=[CH:54][C:44]=2[N:43]=1)=[CH:51][C:50]([C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]([CH:13]4[C@@H:18]5[CH2:19][C@@H:15]([CH2:16][CH2:17]5)[N:14]4[C:20](=[O:31])[C@@H:21]([NH:26][C:27](=[O:30])[O:28][CH3:29])[C@H:22]([O:24][CH3:25])[CH3:23])=[N:10][CH:9]=2)=[C:4]([F:32])[CH:3]=1)=[CH:49][CH:48]=3)=[O:64])=[O:69]

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 67681773Methyl (2S,3R)-1-((1R,4S)-3-(5-(4-bromo-2-fluorophenyl)-1H-imidazol-2-yl)-2-azabicyclo[2.2.1]heptan-2-yl)-3-methoxy-1-oxobutan-2-ylcarbamateHCID 178502307HCID 178502307, Verbindung

Produkt 1

HCID 178502330HCID 178502330, VerbindungAusbeute 48 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

Methyl (2S,3R)-1-((1R,4S)-3-(5-(4-bromo-2-fluorophenyl)-1H-imidazol-2-yl)-2-azabicyclo[2.2.1]heptan-2-yl)-3-methoxy-1-oxobutan-2-ylcarbamate (162 mg, 0.318 mmol), methyl (S)-3-methyl-1-oxo-1-((S)-2-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidin-1-yl)butan-2-ylcarbamate (199 mg, 0.382 mmol), Pd(PPh3)4 (37 mg, 0.0318 mmol) and K2CO3 (2M in H2O, 0.4 mL, 0.8 mmol) were suspended in DME (3 mL). The reaction mixture was degassed with N2 for 11 min then heated to reflux for 2.5 h. Upon completion, the reaction mixture was diluted with MeOH, filtered over a thiol SPE column and concentrated. The crude residue was purified by silica column chromatography (0% to 50% MeOH/EtOAc) to afford the title compound (125 mg, 48%). (ESI) m/z 823 [M+H]+.

Aufarbeitung

  1. customThe reaction mixture was degassed with N2 for 11 min
  2. temperaturethen heated
  3. temperatureto reflux for 2.5 h
  4. additionUpon completion, the reaction mixture was diluted with MeOH
  5. filtrationfiltered over a thiol SPE column
  6. concentrationconcentrated
  7. customThe crude residue was purified by silica column chromatography (0% to 50% MeOH/EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-3098f0f4d53e4869bac850885ab60976
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09156823B2

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