Diisopropylethylamine → {3-[4-(Difluoromethoxy)phenyl]-5-(3-ethoxy-1,2,4-oxadiazol-5-yl)piperidin-1-yl}(1-oxidothio-morpholin-4-yl)methanone

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	5-[4-(Difluoromethoxy)phenyl]-1-[(1-oxidothiomorpholin-4-yl)carbonyl]piperidine-3-carboxylic acid	HCID 58116579	—
Reactant	ethyl N-hydroxyimidocarbamate	HCID 76223295	—
Solvent	Dimethylformamide	HCID 6228	—
Product	{3-[4-(Difluoromethoxy)phenyl]-5-(3-ethoxy-1,2,4-oxadiazol-5-yl)piperidin-1-yl}(1-oxidothio-morpholin-4-yl)methanone	HCID 58116505	—

Reaction Steps

185 mg (0.37 mmol) of the compound from Example 42A and 50 mg (0.48 mmol) of ethyl N′-hydroxyimidocarbamate [G. Zinner, G. Nebel, Arch. Pharm. 1970, 303, 385-390] were initially charged in 1.0 ml of DMF and reacted with 210 mg (0.55 mmol) of HATU and 0.19 ml (143 mg, 1.1 mmol) of N,N-diisopropylethylamine. The mixture was stirred at RT for 15 minutes and then the reaction mixture was partitioned between water and ethyl acetate. The organic phase was washed repeatedly with water, dried over sodium sulphate and concentrated under reduced pressure. The residue was dissolved in 2.0 ml of acetic acid and heated to reflux for 1 h. The reaction mixture was purified by means of preparative HPLC. Yield: 62 mg (33% of theory)

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08084469B2
Source dataset	uspto-grants-2011_12
ORD ID	ord-de8b648eea83467c9b3623dc0bc2a765
Source note	uspto-grants-2011_12