Hydrochloric Acid → Rac-4-{[(2r,3s,4r,5s)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester

Beteiligte Stoffe

Rolle	Name	HCID	Einwaage
Edukt	Hydrochloric Acid	HCID 313	—
Edukt	Diisopropylethylamine	HCID 81531	—
Edukt	4-Amino-1-Boc-piperidine	HCID 1268291	—
Edukt	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Edukt	rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid trifluoroacetic acid	HCID 86640317	—
Lösungsmittel	Dichloromethane	HCID 6344	—
Lösungsmittel	Tetrahydrofuran	HCID 8028	—
Produkt	Rac-4-{[(2r,3s,4r,5s)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester	HCID 59249674	38%

Reaktionsschritte

In a manner similar to the method described in Examples 42c, 42d, rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid trifluoroacetic acid prepared in Example 52c (1.8 g, 3.1 mmol) was reacted with 4-Amino-piperidine-1-carboxylic acid tert-butyl ester(Aldrich, 931 mg, 4.65 g, 4.65 mmol), HATU (2.12 g, 0.92 mmol) and iPr2NEt (2.7 mL, 15.5 mmol) in CH2Cl2 at room temperature overnight, then reacted with aqueous HCl solution in tetrahydrofuran at room temperature for 2 h to give a white solid (0.758 g, 38%).

Herkunft & Nachweise

DOI	10.6084/m9.figshare.5104873.v1
Patentnummer	US08354444B2
Quelldatensatz	uspto-grants-2013_01
ORD ID	ord-09a1a9af766a4a4bb2133569cdf9a1f4
Quellennotiz	uspto-grants-2013_01