Propargyl alcohol → HCID 178522962, compound

HRID 1875171Notes

Reaction equation

HRID 1875171 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:9][C:10]2[C:11]([F:27])=[C:12]([CH2:17][NH:18][C:19]([C:21]3[NH:25][CH:24]=[N:23][C:22]=3[Cl:26])=[O:20])[CH:13]=[CH:14][C:15]=2[Cl:16])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[CH2:28]([OH:31])[C:29]#[CH:30]>C1COCC1.CCOC(C)=O.[Cu]I>[Cl:26][C:22]1[N:23]=[CH:24][NH:25][C:21]=1[C:19]([NH:18][CH2:17][C:12]1[CH:13]=[CH:14][C:15]([Cl:16])=[C:10]([O:9][C:4]2[CH:3]=[C:2]([C:30]#[C:29][CH2:28][OH:31])[CH:7]=[C:6]([Cl:8])[CH:5]=2)[C:11]=1[F:27])=[O:20]

Participants

6

Reactant 2

HCID 7859Propargyl alcoholHCID 178522959HCID 178522959, compound

Product 1

HCID 178522962HCID 178522962, compoundYield 19%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of N-({3-[(3-bromo-5-chlorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)-4-chloro-1H-imidazole-5-carboxamide (100 mg, 0.203 mmol), dichlorobisthiphenylphosphinepalladium(II) (14.22 mg, 0.020 mmol), copper(I) iodide (1.929 mg, 10.13 μmol) and TEA (0.141 ml, 1.013 mmol) in THF (5 ml) was added propargyl alcohol (22.72 mg, 0.405 mmol) and the reaction mixture was stirred at 60° C. overnight. The reaction mixture was diluted with EtOAc and washed with water. The solvent was removed and the crude material was purified via silica gel chromatography to give 4-chloro-N-[(4-chloro-3-{[3-chloro-5-(3-hydroxy-1-propyn-1-yl)phenyl]oxy}-2-fluorophenyl)methyl]-1H-imidazole-5-carboxamide (18 mg, 0.038 mmol, 19% yield).

Workup

  1. washwashed with water
  2. customThe solvent was removed
  3. customthe crude material was purified via silica gel chromatography

Sources & evidence

ORD record
ord-4752d24b96e84017bb920b2a8580d56a
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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