Water → tert-butyl ((1-((3-(2-(cyclopropylamino)-2-oxoethoxy)phenyl)sulfonyl)-5-(2-fluorophenyl)-1H-pyrrol-3-yl)methyl)(methyl)carbamate

HRID 1051008Notes

Reaction equation

HRID 1051008 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:12]([S:13]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([OH:22])[CH:17]=2)(=[O:15])=[O:14])[CH:11]=[C:10]([CH2:23][N:24]([CH3:32])[C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH:9]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:40][C:41]([NH:43][CH:44]1[CH2:46][CH2:45]1)=[O:42].O>CN(C)C=O>[CH:44]1([NH:43][C:41](=[O:42])[CH2:40][O:22][C:18]2[CH:17]=[C:16]([S:13]([N:12]3[C:8]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[F:1])=[CH:9][C:10]([CH2:23][N:24]([CH3:32])[C:25](=[O:31])[O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[CH:11]3)(=[O:14])=[O:15])[CH:21]=[CH:20][CH:19]=2)[CH2:46][CH2:45]1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 167575602-Bromo-N-cyclopropylacetamideHCID 90168587tert-butyl ((5-(2-fluorophenyl)-1-((3-hydroxyphenyl)sulfonyl)-1H-pyrrol-3-yl)methyl)(methyl)carbamate

Product 1

HCID 90168590tert-butyl ((1-((3-(2-(cyclopropylamino)-2-oxoethoxy)phenyl)sulfonyl)-5-(2-fluorophenyl)-1H-pyrrol-3-yl)methyl)(methyl)carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

tert-Butyl ((5-(2-fluorophenyl)-1-((3-hydroxyphenyl)sulfonyl)-1H-pyrrol-3-yl)methyl)(methyl)carbamate 1h (100 mg, 0.22 mmol) was dissolved in 20 mL of N,N-dimethylformamide, followed by addition of cesium carbonate (215 mg, 0.66 mmol) and 2-bromo-N-cyclopropyl-acetamide (61 mg, 0.34 mmol, prepared by a known method disclosed in “Journal of Medicinal Chemistry, 1987, 30(1), 20-24”) and then the reaction solution was stirred for 16 h. 50 mL of water were added, and the reaction solution was extracted with dichloromethane (50 mL×3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the title product tert-butyl ((1-((3-(2-(cyclopropylamino)-2-oxoethoxy)phenyl)sulfonyl)-5-(2-fluorophenyl)-1H-pyrrol-3-yl)methyl)(methyl)carbamate 3a (100 mg, a yellow oil), which was used directly in the next step.

Workup

  1. customprepared by a known method
  2. extractionthe reaction solution was extracted with dichloromethane (50 mL×3)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-817bd2a9c2bf41b68a4bac037394b1f4
Source dataset
uspto-grants-2016_07
Patent number
US09388133B2

Reaction notes

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