Diisopropylethylamine → (2S,4S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-2-cyclohexyl-acetyl}-4-(9H-fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-2-carboxylic acid benzyl ester

https://huagongshe.com/reaction/1481920

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acid	HCID 7009590	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Reactant	(2S,4S)-1-((S)-2-amino-2-cyclohexyl-acetyl)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-2-carboxylic acid benzyl ester hydrochloride	HCID 90220202	—
Solvent	Dimethylformamide	HCID 6228	—
Product	(2S,4S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-2-cyclohexyl-acetyl}-4-(9H-fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-2-carboxylic acid benzyl ester	HCID 90220266	99.7%

Reaction Steps

To a solution of Boc-N-Me-Ala-OH (351 mg, 1.73 mmol) in DMF at 0° C. was added DIPEA (1.27 mL, 8.85 mmol) and HATU (626 mg, 1.65 mmol). After 30 min, (2S,4S)-1-((S)-2-amino-2-cyclohexyl-acetyl)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-2-carboxylic acid benzyl ester hydrochloride (0.97 g, 1.57 mmol) was added, the cooling bath removed and the reaction stirred for 1 h. The mixture was diluted with ethyl acetate, washed with saturated ammonium chloride solution, saturated sodium bicarbonate solution, water, and brine and dried over anhydrous magnesium sulfate. Concentration gave (2S,4S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-2-cyclohexyl-acetyl}-4-(9H-fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-2-carboxylic acid benzyl ester (1.2 g) as an oil that was used without further purification or characterization.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09409888B2
Source dataset	uspto-grants-2016_08
ORD ID	ord-e6662192416d41ff934040ca92d267bd
Source note	uspto-grants-2016_08