Ethyl Acetate → methyl 6-chloro-5-{4-[1-(methylsulfonyl)azetidin-2-yl]phenyl}-1H-indole-3-carboxylate

HRID 338331Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 338331
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13][CH3:14])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1B1OCC(C)(C)CO1.Br[C:24]1[CH:29]=[CH:28][C:27]([CH:30]2[CH2:33][CH2:32][N:31]2[S:34]([CH3:37])(=[O:36])=[O:35])=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>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]>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13][CH3:14])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:24]1[CH:25]=[CH:26][C:27]([CH:30]2[CH2:33][CH2:32][N:31]2[S:34]([CH3:37])(=[O:35])=[O:36])=[CH:28][CH:29]=1

Komponenten

7

Edukt 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 86698665methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylateHCID 866986772-(4-Bromophenyl)-1-(methylsulfonyl)azetidine

Produkt 1

HCID 86698678methyl 6-chloro-5-{4-[1-(methylsulfonyl)azetidin-2-yl]phenyl}-1H-indole-3-carboxylateAusbeute 62 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 21863594Toluene ethanolLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A mixture of methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (100 mg, 0.311 mmol), 2-(4-bromophenyl)-1-(methylsulfonyl)azetidine (108.2 mg, 0.373 mmol), 2.0M potassium carbonate solution (0.5 mL, 1.0 mmol), and Pd(dppf)Cl2 (30 mg, 0.03 mmol) in toluene/ethanol (1.44 mL/0.48 mL) was stirred at 110° C. for 2.5 hours. TLC (petroleum ether/ethyl acetate=3:1) showed that the reaction was complete. The mixture was poured into ethyl acetate and washed with water. The organic phase was dried over sodium sulfate, filtered, and concentrated to give a residue, which was purified by prep-TLC to give the title compound (80 mg, 62% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 12.30-12.10 (s, 1H), 8.2 (s, 1H), 7.92 (s, 1H), 7.65 (s, 1H), 7.55 (d, 2H), 7.45 (d, 2H), 5.35 (m, 1H), 4.32 (m, 1H), 4.0 (m, 1H), 3.75 (s, 3H), 3.15 (m, 2H), 3.05 (s, 3H).

Aufarbeitung

  1. washwashed with water
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a residue, which
  6. customwas purified by prep-TLC

Quellen und Nachweise

ORD-Eintrag
ord-69f7e305fe5045f58cd8fc5300eed468
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889730B2

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