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

HRID 594823Notes

Reaction equation

HRID 594823 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.[CH3:29][NH:30][C:31](=O)[O:32]C1C=CC=CC=1.[OH-].[Na+].O>O1CCCC1>[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][CH3:29])=[O:32])[CH2:25]3)=[CH:11][CH:12]=2)(=[O:5])=[O:6])[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 16034Phenyl MethylcarbamateHCID 118268346(R)-2-(4-(cyclopropylsulfonyl)phenyl)-N-(5-fluorothiazol-2-yl)-3-((S)-pyrrolidin-3-yl)propanamide

Product 1

HCID 73506952(S)-3-((R)-2-(4-(cyclopropylsulfonyl)phenyl)-3-((5-fluorothiazol-2-yl)amino)-3-oxopropyl)-N-methylpyrrolidine-1-carboxamideYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(R)-2-(4-(Cyclopropylsulfonyl)phenyl)-N-(5-fluorothiazol-2-yl)-3-((S)-pyrrolidin-3-yl)propanamide (500 mg, 1.05 mmol) was dissolved in tetrahydrofuran (40 mL), and thereafter, phenyl N-methylcarbamate (636 mg, 4.21 mmol) and an aqueous solution of sodium hydroxide (2 M, 2 mL) were added to the above obtained solution under ice-cold condition. The obtained mixture was stirred for 1.5 hours. Thereafter, water was added to the reaction solution, and the mixed solution was then extracted with ethyl acetate. 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%→15%) to obtain the captioned compound (377 mg, 75%) in the form of a white solid.

Workup

  1. extractionthe mixed solution was then extracted with ethyl acetate
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationwas then concentrated in vacuo
  4. customThe obtained residue was purified by silica gel chromatography (chloroform/methanol=1%→15%)

Sources & evidence

ORD record
ord-99fe6528e4ac430fa3b5da43cc7f505f
Source dataset
uspto-grants-2016_01
Patent number
US09242978B2

Reaction notes

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