Diisopropylethylamine → (S)-N-(2-(4-(4-cyano-1-methyl-1H-imidazo[4,5-c]pyridin-6-yl)-2-(trifluoromethyl)phenoxy)ethyl)-N-ethyl-1-methyl-pyrrolidine-2-carboxamide

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	N-Methyl-L-proline	HCID 643474	—
Reactant	Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 2733084	—
Reactant	1-methyl-6-(4-(2-(ethylamino)ethoxy)-3-(trifluoromethyl)phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile	HCID 59410642	—
Solvent	Dichloromethane	HCID 6344	—
Product	(S)-N-(2-(4-(4-cyano-1-methyl-1H-imidazo[4,5-c]pyridin-6-yl)-2-(trifluoromethyl)phenoxy)ethyl)-N-ethyl-1-methyl-pyrrolidine-2-carboxamide	HCID 59410662	64.5%

Reaction Steps

To a solution of (S)-1-methylpyrrolidine-2-carboxylic acid (16 mg), DIPEA (60 ul) and HBTU (51.7 mg) in dichloromethane (2 ml) was added 1-methyl-6-(4-(2-(ethylamino)ethoxy)-3-(trifluoromethyl)phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile (55 mg). The reaction was left stirring at room temperature for 60 hrs. Reaction mixture was diluted with dichloromethane, washed with sodium bicarbarbonate and water. Organic layer was dried over magnesium sulphate and solvent removed under reduced pressure. The residue was purified by acidic prep HPLC and cationic ion exchange column to yield (S)—N-(2-(4-(4-cyano-1-methyl-1H-imidazo[4,5-c]pyridin-6-yl)-2-(trifluoromethyl)phenoxy)ethyl)-N-ethyl-1-methyl-pyrrolidine-2-carboxamide (40 mg).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08026236B2
Source dataset	uspto-grants-2011_09
ORD ID	ord-ad2bdd5f30b24c18b4a45dbdd52979d7
Source note	uspto-grants-2011_09