Diisopropylethylamine → [(3S,4R)-1-(5'-Cyano-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carbonyl)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl ester

Participants

Role	Name	HCID	Charge
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	1-(5-Cyano-2-pyridinyl)-4-piperidinecarboxylic acid	HCID 16227474	—
Reactant	ethyl-[(3S,4R)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-carbamic acid 4-fluoro-phenyl ester	HCID 58312628	—
Solvent	Dimethylformamide	HCID 6228	—
Product	[(3S,4R)-1-(5'-Cyano-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carbonyl)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl ester	HCID 53246272	63.1%

Reaction Steps

A mixture of 125 mg (0.36 mmol) ethyl-[(3S,4R)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-carbamic acid 4-fluoro-phenyl ester, 137 mg (0.36 mmol) HATU, 63 uL (0.36 mmol) DIPEA and 69.4 mg (0.3 mmol) 5′-cyano-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carboxylic acid in 4 mL DMF was shaken for 2 h at room temperature. The mixture was subjected to purification by preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile, water and NEt3. The product containing fractions were evaporated to yield 106 mg (63%) of the title compound as off-white solid. MS m/e: 560.2 [M+H]+.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09346786B2
Source dataset	uspto-grants-2016_05
ORD ID	ord-73cdaeee63e6462c85f901fc3e109094
Source note	uspto-grants-2016_05