Tetrahydrofuran → (2S, 4R)-1-[5-Chloro-3-(2-methoxypyridin-3-yl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-hydroxypyrrolidine-2-carboxylic acid dimethylamide

HRID 2040427Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2040427
Cl.[CH3:2][N:3]([CH3:12])[C:4]([C@@H:6]1[CH2:10][C@@H:9]([OH:11])[CH2:8][NH:7]1)=[O:5].Cl[C:14]1([C:25]2[C:26]([O:31][CH3:32])=[N:27][CH:28]=[CH:29][CH:30]=2)[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([Cl:23])[CH:21]=2)[NH:16][C:15]1=[O:24].C1COCC1.CCN(C(C)C)C(C)C>ClCCl.O>[CH3:2][N:3]([CH3:12])[C:4]([C@@H:6]1[CH2:10][C@@H:9]([OH:11])[CH2:8][N:7]1[C:14]1([C:25]2[C:26]([O:31][CH3:32])=[N:27][CH:28]=[CH:29][CH:30]=2)[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([Cl:23])[CH:21]=2)[NH:16][C:15]1=[O:24])=[O:5]

Komponenten

7

Edukt 4

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 23535508(2S,4R)-4-hydroxy-N,N-dimethylpyrrolidine-2-carboxamide hydrochlorideHCID 575177583,5-Dichloro-3-(2-methoxypyridin-3-yl)-1,3-dihydroindol-2-one

Produkt 1

HCID 67043814(2S, 4R)-1-[5-Chloro-3-(2-methoxypyridin-3-yl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-hydroxypyrrolidine-2-carboxylic acid dimethylamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

(2S,4R)-4-Hydroxy-pyrrolidine-2-carboxylic acid dimethylamide hydrochloride (0.67 g, 3.44 mmol) was added to a solution of the intermediate from Step B in a mixture of dichloromethane (10 ml), THF (2 ml) and DIPEA (1.6 ml). The reaction mixture was stirred at room temperature for 18 h. After addition of water, the mixture was extracted four times with ethyl acetate. The combined organic phase was dried over magnesium sulfate, filtered and concentrated under reduced pressure. Purification by chromatography (silica gel, 5% MeOH in dichloromethane) resulted in 0.58 g of the more polar diastereomer, 0.2 g of the less polar diastereomer and 0.4 g of a mixture of diastereomers (ratio about 1:1).

Aufarbeitung

  1. extractionthe mixture was extracted four times with ethyl acetate
  2. dry with materialThe combined organic phase was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by chromatography (silica gel, 5% MeOH in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-f3caf17718d944d190c59ad64a27ec8a
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08580842B2

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