Sodium Iodide → 1-cyclopropylethyl N-[4-[3-cyano-1-cyclobutyl-6-[2-(1,2,4-triazol-1-yl)ethoxy]indol-2-yl]phenyl]carbamate

HRID 1009653Notes

Reaction equation

HRID 1009653 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.[I-].[Na+].[Na].[NH:38]1[CH:42]=[N:41][CH:40]=[N:39]1>CC#N.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][N:38]3[CH:42]=[N:41][CH:40]=[N:39]3)[CH:18]=4)=[CH:11][CH:10]=2)[CH3:5])[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 92571H-1,2,4-TriazoleHCID 5360545SodiumHCID 59426250{4-[6-(2-chloroethoxy)-3-cyano-1-cyclobutyl-1H-indol-2-yl]-phenyl}-carbamic acid 1-cyclopropyl-ethyl ester

Product 1

HCID 497725211-cyclopropylethyl N-[4-[3-cyano-1-cyclobutyl-6-[2-(1,2,4-triazol-1-yl)ethoxy]indol-2-yl]phenyl]carbamateYield 29%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6342AcetonitrileSolvent

Procedure

To a solution of {4-[6-(2-chloroethoxy)-3-cyano-1-cyclobutyl-1H-indol-2-yl]-phenyl}-carbamic acid 1-cyclopropyl-ethyl ester (1.46 g, 3.05 mmol) in CH3CN (10 mL) is added sodium iodide (1.84 g, 12.22 mmol). The resulting mixture is stirred at reflux temperature overnight. The solvent is evaporated and the residue is diluted with anhydrous DMF (20 mL) and then used without further purification. To 1 mL of the DMF solution containing the iodoethyl intermediate (0.153 mmol) is added the sodium salt of 1,2,4-triazole (0.31 mmol) and the reaction is stirred at room temperature overnight. The reaction mixture is diluted with 0.5 mL DMF and the desired product is purified by preparative LC to give {4-[3-cyano-1-cyclobutyl-6-(2-[1,2,4]triazol-1-yl-ethoxy)-1H-indol-2-yl]-phenyl}-carbamic acid 1-cyclopropyl-ethyl ester, compound 1329 (23 mg, 29%).

Workup

  1. temperatureat reflux temperature overnight
  2. customThe solvent is evaporated
  3. additionthe residue is diluted with anhydrous DMF (20 mL)
  4. customused without further purification
  5. stirringthe reaction is stirred at room temperature overnight
  6. customthe desired product is purified by preparative LC

Sources & evidence

ORD record
ord-f9655d88b34544f6920df89376d203ec
Source dataset
uspto-grants-2011_07
Patent number
US07973069B2

Reaction notes

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