Dichloromethane → [2-Chloro-5-(3,3-diethoxy-prop-1-ynyl)-pyrimidin-4-yl]cyclopentylamine

Participants

Role	Name	HCID	Charge
Reactant	Dichloromethane	HCID 6344	—
Reactant	Triethylamine	HCID 8471	—
Reactant	3,3-Diethoxypropyne	HCID 66285	—
Reactant	5-Bromo-2-chloro-N-cyclopentyl-4-pyrimidinamine	HCID 44248247	—
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	Tetrahydrofuran	HCID 8028	—
Product	[2-Chloro-5-(3,3-diethoxy-prop-1-ynyl)-pyrimidin-4-yl]cyclopentylamine	HCID 58315397	54.3%

Reaction Conditions

Temperature	60 °C

Reaction Steps

To a stiffed solution of (5-bromo-2-chloro pyrimidin-4-yl)-cyclopentyl-amine (1.00 g, 3.62 mmol) and PdCl2(dppf).dichloromethane (148 mg, 0.181 mmol) in THF (10 mL) is added Et3N (0.757 mL, 5.43 mmol) and 3,3-diethoxy-propyne (0.778 mL, 5.43 mmol) sequentially at room temperature. The mixture is degassed under a stream of N2 and stirred at room temperature for 10 minutes before CuI (29 mg, 0.154 mmol) is added. The reaction vessel is evacuated and back-filled with N2 (×3) and heated at 60° C. for 48 hours. The mixture is allowed to cool, diluted with EtOAc, filtered and partitioned between H2O and ethyl acetate. The phases are separated and the aqueous layer is further extracted with EtOAc (×3), combined organic extracts are dried (MgSO4), filtered and concentrated. The residue is purified by SiO2 chromatography, eluting with a gradient of 5% EtOAc/petrol to 20% EtOAc/petrol to give [2-chloro-5-(3,3-diethoxy-prop-1-ynyl)-pyrimidin-4-yl]-cyclopentyl amine (636 mg, 54%). MS (ESI) m/z 324.2 (M+H)+

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09416136B2
Source dataset	uspto-grants-2016_08
ORD ID	ord-8f7a4cca60ac4383a5439ace8634a329
Source note	uspto-grants-2016_08