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

HRID 594825Notes

Reaction equation

HRID 594825 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.C[Si]([N:33]=[C:34]=[O:35])(C)C.O>ClCCl>[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:34]([NH2:33])=[O:35])[CH2:25]3)=[CH:11][CH:12]=2)(=[O:5])=[O:6])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 962WaterHCID 70696Trimethylsilyl isocyanateHCID 118268346(R)-2-(4-(cyclopropylsulfonyl)phenyl)-N-(5-fluorothiazol-2-yl)-3-((S)-pyrrolidin-3-yl)propanamide

Product 1

HCID 73506954(S)-3-((R)-2-(4-(cyclopropylsulfonyl)phenyl)-3-((5-fluorothiazol-2-yl)amino)-3-oxopropyl)pyrrolidine-1-carboxamideYield 99.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The (R)-2-(4-(cyclopropylsulfonyl)phenyl)-N-(5-fluorothiazol-2-yl)-3-((S)-pyrrolidin-3-yl)propanamide (20.0 mg, 47.2 μmol) obtained in Step 1 of Example 2 was dissolved in dichloromethane (1 mL), and trimethylsilyl isocyanate (25.0 μL, 188 μmol) was then added to the obtained solution. The obtained mixture was stirred for hours. 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 (22.0 mg, 99%) in the form of a white solid.

Workup

  1. extractionthe mixed solution was then extracted with chloroform
  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%→20%)

Sources & evidence

ORD record
ord-65f3e94e2c5743e58b29ae7d74abdb3b
Source dataset
uspto-grants-2016_01
Patent number
US09242978B2

Reaction notes

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