N,N,N',N'-Tetramethylethylenediamine → (S)-tert-butyl 3-((6-cyano-1,7-naphthyridin-8-yl)amino)pyrrolidine-1-carboxylate

Participants

Role	Name	HCID	Charge
Reactant	N,N,N',N'-Tetramethylethylenediamine	HCID 8037	—
Reactant	1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)	HCID 636044	—
Reactant	(S)-tert-butyl 3-((6-bromo-1,7-naphthyridin-8-yl)amino)pyrrolidine-1-carboxylate	HCID 90387016	—
Catalyst	Zinc cyanide (Zn(CN)2)	HCID 11186	—
Catalyst	Bis(dibenzylideneacetone)palladium	HCID 9811564	—
Solvent	Ethyl Acetate	HCID 8857	—
Solvent	N-methyl-2-pyrrolidone	HCID 13387	—
Product	(S)-tert-butyl 3-((6-cyano-1,7-naphthyridin-8-yl)amino)pyrrolidine-1-carboxylate	HCID 90387194	88.9%

Reaction Conditions

Temperature	160 °C

Reaction Steps

A solution of (S)-tert-butyl 3-((6-bromo-1,7-naphthyridin-8-yl)amino)pyrrolidine-1-carboxylate (1141 mg, 2.9 mmol), zinc cyanide (681 mg, 5.80 mmol) and N1,N1,N2,N2-tetramethylethane-1,2-diamine (87 μL, 0.580 mmol) in NMP was degassed with nitrogen for 5 minutes. Xantphos (168 mg, 0.290 mmol) and Pd2dba3 (266 mg, 0.290 mmol) were added and the mixture was heated in a microwave reactor at 160° C. for 10 minutes. The reaction mixture was subsequently diluted with EtOAc. The organic phase was washed with water (2×), dried, and concentrated in vacuo. The crude product was purified by preparative HPLC eluting with a gradient of 45-70% ACN in water (acid mode) to give the title compound as a yellow solid (175 mg, 17.8%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09402841B2
Source dataset	uspto-grants-2016_08
ORD ID	ord-4a69c53d9a894487821cbf59872dd35f
Source note	uspto-grants-2016_08