Potassium Carbonate → (2S,4S)-tert-butyl 4-hydroxy-2-(5-(4-(6-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-4-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate

HRID 1751333Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1751333
[OH:1][C@@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14]2[NH:15][C:16](C3C=CC(B4OC(C)(C)C(C)(C)O4)=CC=3)=[CH:17][N:18]=2)[CH2:3]1.Br[C:35]1[CH:36]=[C:37]2[C:42](=[CH:43][CH:44]=1)[CH:41]=[C:40]([C:45]1[NH:49][C:48]([C@@H:50]3[CH2:54][CH2:53][CH2:52][N:51]3[C:55](=[O:65])[C@@H:56]([NH:60][C:61](=[O:64])[O:62][CH3:63])[CH:57]([CH3:59])[CH3:58])=[N:47][CH:46]=1)[CH:39]=[CH:38]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>[OH:1][C@@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:11])[CH3:12])=[O:8])[C@H:4]([C:14]2[NH:15][C:16]([C:35]3[CH:36]=[CH:37][C:42]([C:35]4[CH:44]=[CH:43][C:42]5[C:37](=[CH:38][CH:39]=[C:40]([C:45]6[NH:49][C:48]([C@@H:50]7[CH2:54][CH2:53][CH2:52][N:51]7[C:55](=[O:65])[C@@H:56]([NH:60][C:61]([O:62][CH3:63])=[O:64])[CH:57]([CH3:59])[CH3:58])=[N:47][CH:46]=6)[CH:41]=5)[CH:36]=4)=[CH:43][CH:44]=3)=[CH:17][N:18]=2)[CH2:3]1

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 59166440Tert-butyl (2S,4S)-4-hydroxy-2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)phenyl)-1H-imidazol-2-YL)pyrrolidine-1-carboxylateHCID 59610262methyl (S)-1-((S)-2-(5-(6-bromonaphthalen-2-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate

Produkt 1

HCID 69675612(2S,4S)-tert-butyl 4-hydroxy-2-(5-(4-(6-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-4-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylateAusbeute 21,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

(2S,4S)-tert-butyl 4-hydroxy-2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (200 mg, 0.44 mmol) and methyl (S)-1-((S)-2-(5-(6-bromonaphthalen-2-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (219 mg, 0.44 mmol) were combined in DME (5 mL). Pd(PPh3)4 (51 mg, 0.0446 mmol) and K2CO3 (2M H2O, 0.73 mL, 1.45 mmol) were added, and the solution was degassed with N2 for 10 min. The solution was heated to 85° C. and stirred o/n. The following morning, the solution was cooled to rt. The solution was diluted with EtOAc, washed with sat. NaHCO3, brine, dried over MgSO4, and concentrated. The residue was purified by silica gel chromatography to yield product (36 mg).

Aufarbeitung

  1. customthe solution was degassed with N2 for 10 min
  2. temperatureThe following morning, the solution was cooled to rt
  3. additionThe solution was diluted with EtOAc
  4. washwashed with sat. NaHCO3, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-11b5914623dd457983e0031cb75195db
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09156823B2

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