Cyclobutanecarboxylic acid → [(3S,4R)-4-(4-Chloro-phenyl)-1-(1-cyclobutanecarbonyl-piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester

Participants

Role	Name	HCID	Charge
Reactant	Cyclobutanecarboxylic acid	HCID 19494	—
Reactant	Diisopropylethylamine	HCID 81531	—
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	[(3S,4R)-4-(4-chloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester	HCID 58303156	—
Solvent	Dimethylformamide	HCID 6228	—
Product	[(3S,4R)-4-(4-Chloro-phenyl)-1-(1-cyclobutanecarbonyl-piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester	HCID 53244786	39%

Reaction Steps

A mixture of 27.6 mg (0.06 mmol) 4-fluorophenyl (3S,4R)-4-(4-chlorophenyl)-1-(piperidine-4-carbonyl)pyrrolidin-3-yl(methyl)carbamate, 0.52 mL (0.072 mmol) HATU (0.136 M in DMF), 12 mg (0.072 mmol) cyclobutanecarboxylic acid and 46.5 mg (0.36 mmol) DIPEA in 1.5 mL DMF was shaken at room temperature over night. The mixture was subjected to preparative HPLC chromatography on reversed phase eluting with a gradient formed from acetonitrile, water and NEt3. The product containing fractions were evaporated to yield 12.5 mg (39%) of the title compounds as off-white solid. MS m/e: 542.3 [M+H]+.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09226916B2
Source dataset	uspto-grants-2016_01
ORD ID	ord-1d21ffdcd27445feb4db374c3a38d0c7
Source note	uspto-grants-2016_01