Diisopropylamine → 5-[3-(3,4-Dihydro-1H-isoquinolin-2-yl)-prop-1-ynyl]-4-(2,2-dimethyl-propylamino)-pyrimidine-2-carbonitrile

https://huagongshe.com/reaction/1984238

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylamine	HCID 7912	—
Reactant	Tris(1,1-dimethylethyl)phosphine	HCID 83681	—
Reactant	2-(Prop-2-yn-1-yl)-1,2,3,4-tetrahydroisoquinoline	HCID 14341294	—
Reactant	5-Bromo-4-(2,2-dimethylpropylamino)pyrimidine-2-carbonitrile	HCID 17968161	—
Catalyst	Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)	HCID 24350	—
Catalyst	Bis(benzonitrile)palladium chloride	HCID 498840	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	5-[3-(3,4-Dihydro-1H-isoquinolin-2-yl)-prop-1-ynyl]-4-(2,2-dimethyl-propylamino)-pyrimidine-2-carbonitrile	HCID 10247897	46.5%

Reaction Steps

2-Prop-2-ynyl-1,2,3,4-tetrahydro-isoquinoline (0.72 mmol), 5-bromo-4-(2,2-dimethyl-propylamino)-pyrimidine-2-carbonitrile (0.86 mmol), Bis(benzonitrile)-palladium(II)chloride (0.02 mmol), copper (I) iodide (0.015 mmol), tri-tert-butylphosphine (0.04 mmol) and diisopropyl amine (0.86 mmol) in dioxane (4 ml) is stirred at room temperature for 2.5 h. After filtration, the reaction mixture is treated with saturated ammonium chloride. The mixture is extracted with AcOEt. The organic layer is washed with brine, dried over magnesium sulfate and evaporated down. The crude product is applied to a column of silica gel, which is eluted with following solvents: n-hexane:AcOEt=1:1 (v/v) and n-hexane:AcOEt=1:5 (v/v). The solvent of the latter effluent is removed by evaporation and dried in vacuo to afford the title compound. yield 46.5%, Rf=0.31 (n-hexane:AcOEt=1:1).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07544688B2
Source dataset	uspto-grants-2009_06
ORD ID	ord-9eb9d5d4a1914b809b7f2df724ecff52
Source note	uspto-grants-2009_06