Potassium Carbonate → 6-Chloro-5-(4-(1-(hydroxymethyl)cyclopropyl)phenyl)-1h-indole-3-carbaldehyde

HRID 338404

Reaktionsgleichung

Reaktionsgleichung von HRID 338404
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][C:3]=1B1OCC(C)(C)CO1.[C:19](=O)([O-])[O-:20].[K+].[K+].Br[C:26]1[CH:31]=[CH:30][C:29]([C:32]2([CH2:35][OH:36])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1>O1CCOCC1.CN(C=O)C.O.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]>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:19]=[O:20])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:26]1[CH:31]=[CH:30][C:29]([C:32]2([CH2:35][OH:36])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1

Komponenten

8

Edukt 3

HCID 11430Potassium CarbonateHCID 20252945(1-(4-Bromophenyl)cyclopropyl)methanolHCID 866987336-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole

Produkt 1

HCID 866987426-Chloro-5-(4-(1-(hydroxymethyl)cyclopropyl)phenyl)-1h-indole-3-carbaldehydeAusbeute 90 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A mixture of 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole (156 mg, 0.60 mmol) and N,N-dimethylformiminium chloride (150 mg, 1.20 mmol) in dry 1,4-dioxane (4 mL) and DMF (0.7 mL) was sealed in a vial and stirred at room temperature for 10 min to give a white slurry. To the reaction mixture was then added 2M aqueous potassium carbonate (2.5 mL, 5 mmol), [1-(4-bromophenyl)cyclopropyl]methanol (140 mg, 0.6 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (50 mg). The reaction mixture was degassed and heated to 90° C. for 30 min. The cooled reaction mixture was diluted with water (20 mL), and then washed with EtOAc (3×20 mL). The combined organic layers were dried and concentrated in vacuo to give crude 6-chloro-5-{4-[1-(hydroxymethyl)cyclopropyl]phenyl}-1H-indole-3-carbaldehyde (160 mg, 90% yield), which was used in the next step without further purification. 1H NMR (400 MHz, DMSO-d6) δ 11.10 (s, 1H), 8.77 (s, 1H), 8.56 (s, 1H), 7.92 (s, 1H), 7.39-7.34 (m, 4H), 4.70 (br.s., 1H), 3.56 (s, 2H), 0.88-0.86 (m, 2H), 0.79-0.77 (m, 2H).

Aufarbeitung

  1. customwas sealed in a vial and
  2. customto give a white slurry
  3. customThe reaction mixture was degassed
  4. temperatureheated to 90° C. for 30 min
  5. customThe cooled reaction mixture
  6. washwashed with EtOAc (3×20 mL)
  7. customThe combined organic layers were dried
  8. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-0e5dc58c16854f80a4de2df8c6d524bf
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889730B2

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