Dichloromethane → 4-cyano-5-ethyl-1-methyl-3-{4-[1-methyl-2-(propane-2-sulfonylamino)-ethyl]-phenyl}-1H-pyrrole-2-carboxylic acid ethyl ester

HRID 1865116Notes

Reaction equation

HRID 1865116 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:24])[C:8]([CH2:22][CH3:23])=[C:9]([C:20]#[N:21])[C:10]=1B1OC(C)(C)C(C)(C)O1)=[O:5])[CH3:2].I[C:26]1[CH:31]=[CH:30][C:29]([CH:32]([CH3:41])[CH2:33][NH:34][S:35]([CH:38]([CH3:40])[CH3:39])(=[O:37])=[O:36])=[CH:28][CH:27]=1.C(Cl)Cl.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.O>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:24])[C:8]([CH2:22][CH3:23])=[C:9]([C:20]#[N:21])[C:10]=1[C:26]1[CH:27]=[CH:28][C:29]([CH:32]([CH3:41])[CH2:33][NH:34][S:35]([CH:38]([CH3:40])[CH3:39])(=[O:36])=[O:37])=[CH:30][CH:31]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 222598982-(4-Iodophenyl) propyl isopropylsulfonamideHCID 579748024-cyano-5-ethyl-1-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrole-2-carboxylic acid ethyl ester

Product 1

HCID 690202154-cyano-5-ethyl-1-methyl-3-{4-[1-methyl-2-(propane-2-sulfonylamino)-ethyl]-phenyl}-1H-pyrrole-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Add 4-cyano-5-ethyl-1-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrole-2-carboxylic acid ethyl ester (0.22 g, 0.65 mmol, prepared in preparation 50), to propane-2-sulfonic acid [2-(4-iodo-phenyl)-propyl]-amide (0.20 g, 0.65 mmol, can be prepared as in J. Med. Chem., 43, 4354 (2000)), [1,1′-bis(diphenyl-phosphino)-ferrocene]dichloropalladium(1H) complex with methylene chloride (1:1) (0.013 g, 0.016 mmol), and 2M aqueous sodium carbonate (1.35 mL, 2.7 mmol) in DMF and heat to 80° C. After 3 hours, cool and pour into water. Extract with ethyl acetate. Wash the combined organics with water, and brine, dry over magnesium sulfate, filter and concentrate under reduced pressure. Purify the residue by flash chromatography (silica gel), eluting with ethyl acetate:hexanes to provide the title compound. Mass spectrum (ES+)=446.3 (M+1).

Workup

  1. temperaturecool
  2. extractionExtract with ethyl acetate
  3. washWash the combined organics with water, and brine
  4. dry with materialdry over magnesium sulfate
  5. filtrationfilter
  6. concentrationconcentrate under reduced pressure
  7. customPurify the residue by flash chromatography (silica gel)
  8. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-b1dd9bd30ea04ab0ae16b769df0e1d14
Source dataset
uspto-grants-2009_12
Patent number
US07625932B2

Reaction notes

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