Diisopropylethylamine → N-[(S)-1-(1-Cyanocyclopropylcarbamoyl)-3,3-difluoro-4-phenylbutyl]-8-azaspiro[4.5]decane-8-carboxamide

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-Amino-1-cyclopropanecarbonitrile hydrochloride	HCID 14586363	—
Reactant	(S)-2-[(8-Azaspiro[4.5]decane-8-carbonyl)amino]-4,4-difluoro-5-phenylpentanoic acid	HCID 66661164	—
Solvent	Dimethylformamide	HCID 6228	—
Product	N-[(S)-1-(1-Cyanocyclopropylcarbamoyl)-3,3-difluoro-4-phenylbutyl]-8-azaspiro[4.5]decane-8-carboxamide	HCID 24996348	—

Reaction Steps

DIPEA (331 μl, 252 mg, 1.95 mmol, 4 eq.), HATU (185 mg, 0.49 mmol, 1 eq.) and 1-aminocyclopropanecarbonitrile hydrochloride (58 mg, 0.49 mmol, 1 eq.) were added successively to a solution of the (S)-2-[(8-azaspiro[4.5]decane-8-carbonyl)amino]-4,4-difluoro-5-phenylpentanoic acid obtained as a crude product (192 mg, 0.49 mmol) in 10 ml of DMF. The reaction mixture was stirred at RT overnight and, the next day, concentrated under reduced pressure. The residue thus obtained was purified by preparative HPLC (gradient: acetonitrile/water and addition of 0.05% TFA). The title compound was obtained in the form of a colorless crystalline material.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08039480B2
Source dataset	uspto-grants-2011_10
ORD ID	ord-de68fad26a344dddb9e252b21ebdf6af
Source note	uspto-grants-2011_10