Sodium Carbonate → 4-[1-(1-benzenesulfonyl-5-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclopentyl-vinyl]-2-fluoro-benzoic acid methyl ester

HRID 1515926Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1515926
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([CH3:19])[CH:18]=[C:13]3[CH:12]=[C:11]2[C:20](OS(C2C=CC(C)=CC=2)(=O)=O)=[CH:21][CH:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:38][O:39][C:40](=[O:57])[C:41]1[CH:46]=[CH:45][C:44](B2OC(C)(C)C(C)(C)O2)=[CH:43][C:42]=1[F:56].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:38][O:39][C:40](=[O:57])[C:41]1[CH:46]=[CH:45][C:44]([C:20]([C:11]2[N:10]([S:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)(=[O:9])=[O:8])[C:14]3=[N:15][CH:16]=[C:17]([CH3:19])[CH:18]=[C:13]3[CH:12]=2)=[CH:21][CH:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)=[CH:43][C:42]=1[F:56]

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 221715283-Fluoro-4-methoxycarbonylphenylboronic acid, pinacol esterHCID 86654520toluene-4-sulfonic acid 1-(1-benzenesulfonyl-5-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclopentyl-vinyl ester

Produkt 1

HCID 672291634-[1-(1-benzenesulfonyl-5-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclopentyl-vinyl]-2-fluoro-benzoic acid methyl esterAusbeute 83 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

To a mixture of toluene-4-sulfonic acid 1-(1-benzenesulfonyl-5-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclopentyl-vinyl ester (prepared as in Example 128, 1.28 g, 2.4 mmol), 2-fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester (2.01 mg, 2.4 mmol) and dichlorobis(triphenylphosphine)palladium (II) (170 mg, 0.24 mmol) in dioxane (10 mL) was added an aqueous sodium carbonate solution (2 M, 3.6 mL, 7.2 mmol). The resulting mixture was subjected to microwave irradiation for 2 h at 100° C. The mixture was diluted with ethyl acetate (100 mL), washed with a saturated aqueous sodium bicarbonate solution (2×30 mL), brine, dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification by flash column chromatography (silica gel from QingDao, 200-300 mesh, 25% ethyl acetate/hexanes) afforded 4-[1-(1-benzenesulfonyl-5-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclopentyl-vinyl]-2-fluoro-benzoic acid methyl ester (1.03 g, 83%) as a light yellow solid: LC/MS m/e calcd for C29H27FN2O4S [M+H]+ 519.61, observed 518.8.

Aufarbeitung

  1. customirradiation for 2 h at 100° C
  2. washwashed with a saturated aqueous sodium bicarbonate solution (2×30 mL), brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customPurification by flash column chromatography (silica gel from QingDao, 200-300 mesh, 25% ethyl acetate/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-6aed4269e60d49af8a0cd6ac58bc5a2d
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08222416B2

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