Dimethyl Sulfoxide → 4-((s)-3-Tert-butoxycarbonylaminopyrrolidin-1-yl)-3-chloro-2-cyclopropylamino-5-fluorobenzoic acid ethyl ester

HRID 10290Notes

Reaction equation

HRID 10290 reaction equation
[CH2:1]([O:3][C:4](=[O:27])[C:5]1[CH:10]=[C:9]([F:11])[C:8]([N:12]2[CH2:16][CH2:15][C@H:14]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]2)=[C:7]([Cl:25])[C:6]=1F)[CH3:2].[CH:28]1([NH2:31])[CH2:30][CH2:29]1.CS(C)=O>C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:27])[C:5]1[CH:10]=[C:9]([F:11])[C:8]([N:12]2[CH2:16][CH2:15][C@H:14]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]2)=[C:7]([Cl:25])[C:6]=1[NH:31][CH:28]1[CH2:30][CH2:29]1)[CH3:2]

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 69828CyclopropylamineHCID 586818944-[(S)-3-tert-Butoxycarbonylaminopyrrolidin-1-yl]-3-chloro-2,5-difluorobenzoic acid ethyl ester

Product 1

HCID 578326504-((s)-3-Tert-butoxycarbonylaminopyrrolidin-1-yl)-3-chloro-2-cyclopropylamino-5-fluorobenzoic acid ethyl esterYield 43.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-[(S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-3-chloro-2,5-difluorobenzoic acid ethyl ester (Example 2c, 9.34 g, 23.1 mmol), cyclopropylamine (16 mL, 228 mmol), and dimethyl sulfoxide (30 mL) is heated in a sealed tube at 110° C. for 3 days. After cooling to room temperature, the reaction mixture is diluted with ethyl acetate and washed with saturated NaHCO3, water, and brine. The organic layer is dried over MgSO4, filtered, and the filtrate is concentrated to afford a brown residue. The residue is then purified via flash column chromatography (1:1 ethyl acetate/hexanes) to afford the title compound (4.41 g). MS CI: m/z 442 (MH+).

Workup

  1. washwashed with saturated NaHCO3, water, and brine
  2. dry with materialThe organic layer is dried over MgSO4
  3. filtrationfiltered
  4. concentrationthe filtrate is concentrated
  5. customto afford a brown residue
  6. customThe residue is then purified via flash column chromatography (1:1 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-17cd02a021354dd183a83816d55b9074
Source dataset
uspto-grants-2006_08
Patent number
US07094780B1

Reaction notes

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