Diisopropylethylamine → 4-[(R)-2-({4-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-7-methyl-quinoline-2-carbonyl}-amino)-3-fluoro-propionyl]-piperazine-1-carboxylic acid butyl ester

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Sodium Bicarbonate	HCID 516892	—
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	4-((R)-2-Amino-3-fluoro-propionyl)piperazine-1-carboxylic acid butyl ester	HCID 68598169	—
Reactant	4-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-7-methyl-quinoline-2-carboxylic acid	HCID 68599277	—
Solvent	Dimethylformamide	HCID 6228	—
Product	4-[(R)-2-({4-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-7-methyl-quinoline-2-carbonyl}-amino)-3-fluoro-propionyl]-piperazine-1-carboxylic acid butyl ester	HCID 68602093	—

Reaction Steps

To a solution of 108 mg 4-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-7-methyl-quinoline-2-carboxylic acid in 2.5 ml DMF were added 134 μl DIPEA and 97 mg HATU. After 5 minutes 102 mg 4-((R)-2-Amino-3-fluoro-propionyl)piperazine-1-carboxylic acid butyl ester hydrotrifluoroacetate were added and the mixture stirred for 3 h before 2 ml of saturated aqueous NaHCO3 were added. The mixture was loaded on a chem Elute® cartridge and the crude product eluted with DCM. Further purification was performed by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA). The fractions containing the product were lyophilized to yield the pure product. Yield: 76 mg MS(ES+): m/e=669.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08669266B2
Source dataset	uspto-grants-2014_03
ORD ID	ord-fd67a21426e9477187e698a2bbd2a6e5
Source note	uspto-grants-2014_03