1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Letaxaban

HRID 20223Notes

Reaction equation

HRID 20223 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([S:12]([CH2:15][C@@H:16]([OH:20])[C:17]([OH:19])=O)(=[O:14])=[O:13])[CH:6]=[CH:5]2.[NH:21]1[CH2:26][CH2:25][CH:24]([N:27]2[CH2:32][CH2:31][CH2:30][NH:29][C:28]2=[O:33])[CH2:23][CH2:22]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([S:12]([CH2:15][C@@H:16]([OH:20])[C:17]([N:21]1[CH2:26][CH2:25][CH:24]([N:27]3[CH2:32][CH2:31][CH2:30][NH:29][C:28]3=[O:33])[CH2:23][CH2:22]1)=[O:19])(=[O:13])=[O:14])[CH:6]=[CH:5]2

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 155726661-(Piperidin-4-yl)-1,3-diazinan-2-oneHCID 66854329(2S)-3-[(6-chloro-2-naphthyl)sulfonyl]-2-hydroxypropionic acid

Product 1

HCID 11641515Letaxaban

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(2S)-3-[(6-Chloronaphthalen-2-yl)sulfony]-2-hydroxypropionic acid, 1-(piperidin-4-yl)tetrahydropyrimidin-2(1H)-one, and HOBt (23.0 g) were dissolved in DMF, WSC was added thereto, and the mixture was stirred at room temperature for 15 hours. The reaction mixture was concentrated under reduced pressure, diluted with an aqueous sodium bicarbonate solution, and extracted with dichloromethane. The extract was washed with an aqueous 5% citric acid solution and saturated saline solution, and dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate to ethyl acetate/methanol=10/1) to obtain the title compound as a colorless powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additiondiluted with an aqueous sodium bicarbonate solution
  3. extractionextracted with dichloromethane
  4. washThe extract was washed with an aqueous 5% citric acid solution and saturated saline solution
  5. dry with materialdried over sodium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate to ethyl acetate/methanol=10/1)

Sources & evidence

ORD record
ord-b9cf14e9afb6498eb36a38b403161087
Source dataset
uspto-grants-2010_06
Patent number
US07745623B2

Reaction notes

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