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 2040424ノート

反応式

HRID 2040424 の反応式
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]

参加物

7

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒

実験手順

(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).

後処理

  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)

出典と根拠

ORDレコード
ord-cdad3e394a1746168cee2b4dcaf60a7e
出典データセット
uspto-grants-2013_11
特許番号
US08580842B2

反応ノート

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