Water → (S)-3-((R)-2-(4-(cyclopropylsulfonyl)phenyl)-3-((5-fluorothiazol-2-yl)amino)-3-oxopropyl)-N-hydroxypyrrolidine-1-carboxamide

HRID 594826Notes

Reaction equation

HRID 594826 reaction equation
[CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([C@@H:13]([CH2:23][C@H:24]3[CH2:28][CH2:27][NH:26][CH2:25]3)[C:14]([NH:16][C:17]3[S:18][C:19]([F:22])=[CH:20][N:21]=3)=[O:15])=[CH:9][CH:8]=2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.[OH:29][NH:30][C:31](=O)[O:32]C1C=CC=CC=1.O>C(O)C>[CH:1]1([S:4]([C:7]2[CH:8]=[CH:9][C:10]([C@H:13]([C:14]([NH:16][C:17]3[S:18][C:19]([F:22])=[CH:20][N:21]=3)=[O:15])[CH2:23][C@H:24]3[CH2:28][CH2:27][N:26]([C:31]([NH:30][OH:29])=[O:32])[CH2:25]3)=[CH:11][CH:12]=2)(=[O:5])=[O:6])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 962WaterHCID 148233Phenyl N-hydroxycarbamateHCID 118268346(R)-2-(4-(cyclopropylsulfonyl)phenyl)-N-(5-fluorothiazol-2-yl)-3-((S)-pyrrolidin-3-yl)propanamide

Product 1

HCID 73507173(S)-3-((R)-2-(4-(cyclopropylsulfonyl)phenyl)-3-((5-fluorothiazol-2-yl)amino)-3-oxopropyl)-N-hydroxypyrrolidine-1-carboxamideYield 54.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

The (R)-2-(4-(cyclopropylsulfonyl)phenyl)-N-(5-fluorothiazol-2-yl)-3-((S)-pyrrolidin-3-yl)propanamide (39.1 mg, 92.3 μmol) obtained in Step 1 of Example 2 was dissolved in ethanol (2 mL), and phenyl N-hydroxycarbamate (56.0 mg, 366 μmol) was then added to the obtained solution. The obtained mixture was stirred for 5 hours at reflux. Thereafter, water was added to the reaction solution, and the mixed solution was then extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, and was then concentrated in vacuo. The obtained residue was purified by silica gel chromatography (chloroform/methanol=1%→20%) to obtain the captioned compound (24.2 mg, 54%) in the form of a white solid.

Workup

  1. temperatureat reflux
  2. extractionthe mixed solution was then extracted with chloroform
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationwas then concentrated in vacuo
  5. customThe obtained residue was purified by silica gel chromatography (chloroform/methanol=1%→20%)

Sources & evidence

ORD record
ord-089f997719a64bad955e2fc4255e1604
Source dataset
uspto-grants-2016_01
Patent number
US09242978B2

Reaction notes

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