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 601761Notes

Reaction equation

HRID 601761 reaction equation
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]

Participants

7

Reactant 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

Product 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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

(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).

Workup

  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)

Sources & evidence

ORD record
ord-adb3b0b5ef6349c0ae3ce98b588b419e
Source dataset
uspto-grants-2011_03
Patent number
US07902379B2

Reaction notes

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