5-bromo-6-chloro-1H-indole-3-carbaldehyde → 5-{4-[(1-acetylazetidin-3-yl)methoxy]phenyl}-6-chloro-1H-indole-3-carbaldehyde

HRID 338242

Reaktionsgleichung

Reaktionsgleichung von HRID 338242
CC1(C)COB([C:8]2[CH:22]=[CH:21][C:11]([O:12][CH2:13][CH:14]3[CH2:17][N:16]([C:18](=[O:20])[CH3:19])[CH2:15]3)=[CH:10][CH:9]=2)OC1.Br[C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][C:33]=1[Cl:34])[NH:30][CH:29]=[C:28]2[CH:35]=[O:36]>C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1.C(O)C.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]>[C:18]([N:16]1[CH2:15][CH:14]([CH2:13][O:12][C:11]2[CH:10]=[CH:9][C:8]([C:25]3[CH:26]=[C:27]4[C:31](=[CH:32][C:33]=3[Cl:34])[NH:30][CH:29]=[C:28]4[CH:35]=[O:36])=[CH:22][CH:21]=2)[CH2:17]1)(=[O:20])[CH3:19]

Komponenten

7

Edukt 2

HCID 866985665-bromo-6-chloro-1H-indole-3-carbaldehydeHCID 866985861-(3-((4-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)phenoxy)methyl)azetidin-1-yl)ethanone

Produkt 1

HCID 866985875-{4-[(1-acetylazetidin-3-yl)methoxy]phenyl}-6-chloro-1H-indole-3-carbaldehydeAusbeute 52 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 702EthanolLösungsmittelHCID 1140TolueneLösungsmittelHCID 11430Potassium CarbonateLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

To a mixture of 1-(3-{[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenoxy]methyl}azetidin-1-yl)ethanone (160 mg, 0.64 mmol), 5-bromo-6-chloro-1H-indole-3-carbaldehyde (165.4 mg, 0.64 mmol) in 2M aqueous potassium carbonate (1.3 mL, 2M), toluene (3 mL) and ethanol (1 mL) was added [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (46 mg, 0.064 mmol). The mixture was degassed with nitrogen for 5 minutes. The mixture was heated to 110° C. and stirred under microwave irradiation for 2 hours. The cooled reaction mixture was extracted with ethyl acetate (10 mL×3). The combined organic layers was dried over sodium sulfate, filtered, and concentrated in vacuo to give a brown residue. The residue was purified by flash column chromatography (petroleum ether/ethyl acetate=20:1 to 3:1) to give 5-{4-[(1-acetylazetidin-3-yl)methoxy]phenyl}-6-chloro-1H-indole-3-carbaldehyde (127 mg, 52%) as a brown solid. 1H NMR (400 MHz, CDCl3) δ 10.01 (s, 1H), 7.60-7.39 (m, 5H), 6.99 (d, 2H), 4.30 (m, 1H), 4.20-4.09 (m, 4H), 3.93 (m, 1H), 3.07 (m, 1H), 1.91 (s, 3H).

Aufarbeitung

  1. customThe mixture was degassed with nitrogen for 5 minutes
  2. customThe cooled reaction mixture
  3. extractionwas extracted with ethyl acetate (10 mL×3)
  4. dry with materialThe combined organic layers was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a brown residue
  8. customThe residue was purified by flash column chromatography (petroleum ether/ethyl acetate=20:1 to 3:1)

Quellen und Nachweise

ORD-Eintrag
ord-519d1027dca74b1297a0c1b1a05895d9
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889730B2

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