Propargyl alcohol → 3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenyl)prop-2-yn-1-ol

Participants

Role	Name	HCID	Charge
Reactant	Propargyl alcohol	HCID 7859	—
Reactant	Pyrrolidine	HCID 31268	—
Reactant	2-(4-bromo-2,6-difluorobenzylthio)-5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole	HCID 66740578	—
Catalyst	Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)	HCID 24350	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Dimethylformamide	HCID 6228	—
Product	3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenyl)prop-2-yn-1-ol	HCID 66740045	94.9%

Reaction Conditions

Temperature	80 °C

Reaction Steps

A mixture of 2-(4-bromo-2,6-difluorobenzylthio)-5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole (0.79 g, 1.35 mmol), propargyl alcohol (122 μL, 2.03 mmol), pyrrolidine (169 μL, 2.03 mmol), CuI (26 mg, 0.13 mmol) and PdCl2(dppf)2 (50 mg, 0.07 mmol) in DMF (6.80 mL) was purged with argon and then heated to 80° C. for 3 h. The reaction mixture was filtered through to remove solids. The filter agent was rinsed with EtOAc and the filtrate was extracted with EtOAc (3×75 mL). The combined extracts were washed with water and brine, dried over anhyd Na2SO4, concentrated and purified by flash chromatography (80% EtOAc/hexanes) to get 3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenyl)prop-2-yn-1-ol (714 mg, 94%) as a yellow solid. MS (EI) m/z 557 (MH+).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08846739B2
Source dataset	uspto-grants-2014_09
ORD ID	ord-e0b95edb91504a56a2c8bb714c917c85
Source note	uspto-grants-2014_09