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

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	1-(Dimethylamino)cyclopropane-1-carboxylic acid	HCID 386199	—
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-methyl-6-(4-(2-(methylamino)ethoxy)-3-(trifluoromethyl)-phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile	HCID 59410639	—
Solvent	Diethyl Ether	HCID 3283	—
Solvent	Ethyl Acetate	HCID 8857	—
Solvent	N-methyl-2-pyrrolidone	HCID 13387	—
Product	N-(2-(4-(4-cyano-1-methyl-1H-imidazo[4,5-c]pyridin-6-yl)-2-(trifluoromethyl)phenoxy)ethyl)-1-(dimethylamino)-N-methylcyclopropane-carboxamide	HCID 59410641	22%

Reaction Steps

1-Methyl-6-(4-(2-(methylamino)ethoxy)-3-(trifluoromethyl)phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile (54 mg), 1-(dimethylamino)cyclopropane-carboxylic acid (37.2 mg), HATU (82 mg) and DIPEA (0.119 ml) were combined in NMP (2 ml) and stirred at room temperature for 16 hours. The reaction mixture was diluted with EtOAc (25 mL) and washed with 1:1 saturated sodium bicarbonate solution/water (3×15 mL). Organics were dried over sodium sulphate and solvent evaporated under reduced pressure. Purification by flash chromatography (10 g silica column, DCM to 5% MeOH in DCM gradient) followed by preparative HPLC (acidic) and SCX afforded N-(2-(4-(4-cyano-1-methyl-1H-imidazo[4,5-c]pyridin-6-yl)-2-(trifluoromethyl)phenoxy)ethyl)-1-(dimethylamino)-N-methylcyclopropane-carboxamide (22% yield) as a white solid after trituration with ether and oven drying.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08026236B2
Source dataset	uspto-grants-2011_09
ORD ID	ord-472a3a2fd6d0491291a28075a3cb5f03
Source note	uspto-grants-2011_09