Sodium Iodide → {4-[3-Cyano-1-cyclobutyl-6-(2-methanesulfonyl-ethoxy)-1H-indol-2-yl]-phenyl}-carbamic acid 1-cyclopropylethyl ester

HRID 502268Notes

Reaction equation

HRID 502268 reaction equation
[CH:1]1([CH:4]([O:6][C:7](=[O:34])[NH:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[N:16]([CH:30]4[CH2:33][CH2:32][CH2:31]4)[C:17]4[C:22]([C:23]=3[C:24]#[N:25])=[CH:21][CH:20]=[C:19]([O:26][CH2:27][CH2:28]Cl)[CH:18]=4)=[CH:11][CH:10]=2)[CH3:5])[CH2:3][CH2:2]1.CN(C=O)C.CC#N.[I-].[Na+].[CH3:45][S:46]([O-:48])=[O:47].[Na+]>Cl.CN(C=O)C>[CH:1]1([CH:4]([O:6][C:7](=[O:34])[NH:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[N:16]([CH:30]4[CH2:33][CH2:32][CH2:31]4)[C:17]4[C:22]([C:23]=3[C:24]#[N:25])=[CH:21][CH:20]=[C:19]([O:26][CH2:27][CH2:28][S:46]([CH3:45])(=[O:48])=[O:47])[CH:18]=4)=[CH:11][CH:10]=2)[CH3:5])[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 2733271Sodium methanesulfinateHCID 21891449acetonitrile N,N-dimethylformamideHCID 59426250{4-[6-(2-chloroethoxy)-3-cyano-1-cyclobutyl-1H-indol-2-yl]-phenyl}-carbamic acid 1-cyclopropyl-ethyl ester

Product 1

HCID 68425805{4-[3-Cyano-1-cyclobutyl-6-(2-methanesulfonyl-ethoxy)-1H-indol-2-yl]-phenyl}-carbamic acid 1-cyclopropylethyl esterYield 35%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent2×HCID 6228DimethylformamideSolvent

Procedure

To a solution of {4-[6-(2-Chloro-ethoxy)-3-cyano-1-cyclobutyl-1H-indol-2-yl]-phenyl}-carbamic acid 1-cyclopropyl-ethyl ester (800 mg, 1.67 mmol) in 1:4 DMF/CH3CN (8 mL) is added sodium iodide (2.50 g, 16.7 mmol). The resulting mixture was refluxed overnight. An aqueous workup was performed in 0.5M HCl (200 mL) and extracted with EtOAc (2×100 mL). Organic layers were combined, dried over MgSO4 and concentrated. Solid product was triturated with ether and used without further purification. To 4 mL of a DMF solution containing the iodoethyl intermediate (0.56 mmol) was added the sodium methane sulfinate (113 mg, 1.11 mmol), and the reaction was stirred at room temperature overnight. An aqueous workup was performed in 0.5M HCl (200 mL) and extracted with EtOAc (2×100 mL). The organic layers were combined, dried over MgSO4 and concentrated. The mixture was purified over silica gel column (CH2Cl2) to provide 100 mg (35% yield) of {4-[3-Cyano-1-cyclobutyl-6-(2-methanesulfonyl-ethoxy)-1H-indol-2-yl]-phenyl}-carbamic acid 1-cyclopropylethyl ester, as an off-white powder.

Workup

  1. temperatureThe resulting mixture was refluxed overnight
  2. extractionextracted with EtOAc (2×100 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customSolid product was triturated with ether
  6. customused without further purification
  7. extractionextracted with EtOAc (2×100 mL)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customThe mixture was purified over silica gel column (CH2Cl2)

Sources & evidence

ORD record
ord-f12f64a6f62c4ab7a8b44099dec0ee6c
Source dataset
uspto-grants-2010_08
Patent number
US07772271B2

Reaction notes

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