Diisopropylethylamine → 2-{4-(2-({(2-(4-Chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyano-6-(pyrrolidin-1-yl)pyridin-4-yl)phenoxy}ethyl N2,N6-bis(tert-butoxycarbonyl)-L-lysyl-L-alaninate

https://huagongshe.com/reaction/1968306

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
Reactant	1-Hydroxybenzotriazole hydrate	HCID 2796029	—
Reactant	(2S)-2,6-bis((((tert-butoxy)carbonyl)amino))hexanoic acid	HCID 7349648	—
Reactant	2-{4-(2-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyano-6-(pyrrolidin-1-yl)pyridin-4-yl)phenoxy}ethyl L-alaninate trifluoroacetate	HCID 68764702	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Acetonitrile--water (1/1)	HCID 18373917	—
Product	2-{4-(2-({(2-(4-Chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyano-6-(pyrrolidin-1-yl)pyridin-4-yl)phenoxy}ethyl N2,N6-bis(tert-butoxycarbonyl)-L-lysyl-L-alaninate	HCID 86643850	—

Reaction Steps

166 mg (0.478 mmol) of N2,N6-bis(tert-butoxycarbonyl)-L-lysine were initially charged in 6.4 ml of DMF. 88 mg (0.652 mmol) of 1-hydroxy-1H-benzotriazole hydrate, 100 mg (0.522 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 0.379 ml (2.173 mmol) of N,N-diisopropylethylamine were added, 330 mg (0.435 mmol) of 2-{4-(2-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyano-6-(pyrrolidin-1-yl)pyridin-4-yl)phenoxy}ethyl L-alaninate trifluoroacetate (Example 40) were then added and the mixture was stirred at RT overnight. Water/acetonitrile was added to the reaction solution in such an amount that a clear solution was formed. This was purified by preparative HPLC (acetonitrile/water+0.1% TFA). This gave 216 mg (44% of theory) of the target compound.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08420825B2
Source dataset	uspto-grants-2013_04
ORD ID	ord-c58d413322fc4366966248f344e111b4
Source note	uspto-grants-2013_04