N,N-Dimethylethylenediamine → (1R,2S)-ethyl 1-((2S,4R)-1-((S)-2-(2-methylpyrimidine-5-carboxamido)non-8-enoyl)-4-(3-(benzo[d]thiazol-2-yl)quinoxalin-2-yloxy)pyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate

Participants

Role	Name	HCID	Charge
Reactant	N,N-Dimethylethylenediamine	HCID 66053	—
Reactant	3a,4,7,7a-Tetrahydro-2-hydroxy-4,7-methano-1H-isoindole-1,3(2H)-dione	HCID 89529	—
Reactant	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
Reactant	(s)-2-(2-Methylpyrimidine-5-carboxamido)non-8-enoic acid	HCID 67296764	—
Reactant	(1R,2S)-ethyl 1-((2S,4R)-4-(3-(benzo[d]thiazol-2-yl)quinoxalin-2-yloxy)pyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate	HCID 90815537	—
Solvent	Dimethylformamide	HCID 6228	—
Product	(1R,2S)-ethyl 1-((2S,4R)-1-((S)-2-(2-methylpyrimidine-5-carboxamido)non-8-enoyl)-4-(3-(benzo[d]thiazol-2-yl)quinoxalin-2-yloxy)pyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate	HCID 90855515	—

Reaction Steps

(1R,2S)-ethyl 1-((2S,4R)-4-(3-(benzo[d]thiazol-2-yl)quinoxalin-2-yloxy)pyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate, the title compound of Example 42a, N-hydroxy-5-norbornene-2,3-dicarboximide, and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride can be mixed and stirred in DMF for hours, followed by addition of N,N-dimethylethylene diamine. The reaction produces (1R,2S)-ethyl 1-((2S,4R)-1-((S)-2-(2-methylpyrimidine-5-carboxamido)non-8-enoyl)-4-(3-(benzo[d]thiazol-2-yl)quinoxalin-2-yloxy)pyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate, which can be dissolved in isopropyl acetate and extracted with aqueous H3PO4, and then extracted with aqueous K2HPO4.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09309279B2
Source dataset	uspto-grants-2016_04
ORD ID	ord-bdae24be06e44b2da49aff7b638d7864
Source note	uspto-grants-2016_04