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

HRID 601761Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 601761
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:33][CH3:34])=[N:27][C:28]([O:31][CH3:32])=[N: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:33][CH3:34])=[N:27][C:28]([O:31][CH3:32])=[N: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 575177543,5-Dichloro-3-(2,4-dimethoxypyrimidin-5-yl)-1,3-dihydroindol-2-one

Produkt 1

HCID 67044344(2S, 4R)-1-[5-Chloro-3-(2,4-dimethoxypyrimidin-5-y)-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 (0.39 g, 2.0 mmol) was added to a solution of the intermediate from step B in a mixture of dichloromethane (4 ml), THF (1 ml) and DIPEA (1 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, 7% MeOH in dichloromethane) resulted in 0.45 g of the mixture of diastereomers (ratio about 2:1).

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, 7% MeOH in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-adb3b0b5ef6349c0ae3ce98b588b419e
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07902379B2

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