Cesium carbonate → (2S,4R)-4-(Isoquinolin-6-ylamino)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

Participants

Role	Name	HCID	Charge
Reactant	Cesium carbonate	HCID 10796	—
Reactant	6-Bromoisoquinoline	HCID 313681	—
Reactant	Methyl (2S,4R)-4-aminopyrrolidine-2-carboxylate hydrochloride, N1-BOC protected	HCID 17750455	—
Solvent	Dimethylformamide	HCID 6228	—
Product	(2S,4R)-4-(Isoquinolin-6-ylamino)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester	HCID 25108913	—

Reaction Conditions

Temperature	100 °C

Reaction Steps

124 mg of 6-bromoisoquinoline (3), 488 mg of cesium carbonate and 202 mg (2S,4R)-4-amino-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester hydrochloride were dissolved in 6 ml of DMF and degassed. 46 mg Palladium acetate and 132 mg of Xanthphos were added and the mixture was stirred at 100° C. for 5 h. After cooling to rt the mixture was filtrated, evaporated and the residue was purified by chromatography on silica gel (50% ethyl acetate in heptane to 100% ethyl acetate). To obtain (2S,4R)-4-(Isoquinolin-6-ylamino)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester as a colourless oil.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08772492B2
Source dataset	uspto-grants-2014_07
ORD ID	ord-e7b4cdb0bc3c4bf3817a3a2f4cb62876
Source note	uspto-grants-2014_07