Diisopropylamine → N-methoxy-N-methyl-2-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}-1-benzofuran-5-carboxamide

HRID 494829

Reaktionsgleichung

Reaktionsgleichung von HRID 494829
[OH:1][C:2]1[CH:13]=[CH:12][C:5]([C:6]([N:8]([O:10][CH3:11])[CH3:9])=[O:7])=[CH:4][C:3]=1I.[CH2:15]([N:19]1[CH2:23][CH2:22][CH2:21][C@H:20]1[CH3:24])[CH2:16][C:17]#[CH:18].CC1C=CC(P(C2C=CC(C)=CC=2)C2C=CC(C)=CC=2)=CC=1.C(NC(C)C)(C)C>C(#N)C.CC([O-])=O.CC([O-])=O.[Pd+2].[Cu](I)I>[CH3:11][O:10][N:8]([CH3:9])[C:6]([C:5]1[CH:12]=[CH:13][C:2]2[O:1][C:17]([CH2:16][CH2:15][N:19]3[CH2:23][CH2:22][CH2:21][C@H:20]3[CH3:24])=[CH:18][C:3]=2[CH:4]=1)=[O:7]

Komponenten

8

Edukt 4

HCID 7912DiisopropylamineHCID 13956Phosphine, tris(4-methylphenyl)-HCID 11367023(R)-1-(But-3-yn-1-yl)-2-methylpyrrolidineHCID 117712104-hydroxy-3-iodo-N-methoxy-N-methylbenzamide

Produkt 1

HCID 11438480N-methoxy-N-methyl-2-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}-1-benzofuran-5-carboxamideAusbeute 10,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 83717Copper iodideKatalysatorHCID 167845palladium(II) acetateKatalysatorHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

The product from Example 71D (11.6 g, 37.77 mmol) in acetonitrile (50 mL) was treated sequentially with a 0.12M solution of the product from Example 68B (378 mL, 45.33 mmol), Pd(OAc)2 (0.254 g, 1.13 mmol), tris(4-methylphenyl)phosphine (0.518 g, 1.699 mmol), and diisopropyl amine (39.7 mL, 283.3 mmol). After stirring at 25° C. for 10 minutes, the mixture was treated with copper iodide (2.158 g, 11.33 mmol) and heated at 50° C. in an inert atmosphere for 18 hours. The reaction mixture was allowed to cool to room temperature, filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was purified on silica gel using 95% DCM, 9.9% MeOH, 0.1% NH4OH to provide the title compound (1.22 g, 10.2% yield). 1HNMR (300MHz, CD3OD) δ 1.18 (d, 3H, J=6.1 Hz), 1.47 (m, 1H), 1.78 (m, 2H), 1.91-2.34 (m, 2H), 2.50 (m, 2H) 3.06 (m, 2H), 3.26 (m, 2H), 3.38 (s, 3H), 3.59 (s, 3H), 6.63 (s, 1H), 7.51 (q, 2H), 7.84 (1H); MS (ESI) m/z 317.2 (M+H)+.

Aufarbeitung

  1. temperatureheated at 50° C. in an inert atmosphere for 18 hours
  2. temperatureto cool to room temperature
  3. filtrationfiltered through celite
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe residue was purified on silica gel using 95% DCM, 9.9% MeOH, 0.1% NH4OH

Quellen und Nachweise

ORD-Eintrag
ord-dc151b476a42447c9c038bff6c8daf99
Quelldatensatz
uspto-grants-2009_05
Patentnummer
US07538138B2

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