Hydrochloric Acid → (S)-3-((S)-1-Cyclopentyloxycarbonyl-3-methyl-butylcarbamoyl)-7-nitro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

Participants

Role	Name	HCID	Charge
Reactant	Hydrochloric Acid	HCID 313	—
Reactant	Triethylamine	HCID 8471	—
Reactant	1-Hydroxybenzotriazole	HCID 75771	—
Reactant	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
Reactant	(S)-cyclopentyl 2-amino-4-methylpentanoate	HCID 53718217	—
Reactant	(S)-2-(tert-butoxycarbonyl)-7-nitro-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid	HCID 67052655	—
Solvent	Dichloromethane	HCID 6344	—
Product	(S)-3-((S)-1-Cyclopentyloxycarbonyl-3-methyl-butylcarbamoyl)-7-nitro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester	HCID 57971746	82%

Reaction Steps

(S)-7-Nitro-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid-2-tert-butyl ester (2.5 g, 7.76 mmol) was dissolved in DCM (100 ml). HOBt (1.16 g, 8.53 mmol) was added, L-leucine cyclopentyl ester (3.19 g, 8.53 mmol) was added followed by triethylamine (2.38 ml, 17.1 mmol). EDCl.HCl (1.46 g, 8.5 mmol) was added and the reaction stirred at room temperature for 16 h. To the reaction was added DCM (100 ml) and the organic layer washed with water (3×300 ml), dried with Na2SO4 and the solvent removed in vacuo. The crude product was purified by chromatography (EtOAc:heptane 1:2→EtOAc) to give the required product 3.14 g (82% yield), LCMS purity 100%, m/z 504 [M++H]+

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09133104B2
Source dataset	uspto-grants-2015_09
ORD ID	ord-47bf9ed084ef41df8aad08bb1689e0cf
Source note	uspto-grants-2015_09