Diisopropylethylamine → 4-((4-Chlorobenzyl)oxy)-1-(2-((1RS,2RS)-2-fluorocyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one

https://huagongshe.com/reaction/2202959

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Calcium Chloride	HCID 5284359	—
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	rac-(1R,2S)-2-fluorocyclopropane-1-carboxylic acid	HCID 10103129	—
Reactant	4-(4-Chlorobenzyloxy)-1-(4-amino-3-(methylamino)phenyl)pyridin-2(1h)-one	HCID 89690258	—
Solvent	Dimethylformamide	HCID 6228	—
Product	4-((4-Chlorobenzyl)oxy)-1-(2-((1RS,2RS)-2-fluorocyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one	HCID 121386231	10.8%

Reaction Conditions

Temperature	90 °C

Reaction Steps

A mixture of 1-(4-amino-3-(methylamino)phenyl)-4-((4-chlorobenzyl)oxy)pyridin-2(1H)-one (200 mg), HATU (224 mg), trans-2-fluoro-cyclopropanecarboxylic acid (100 mg), N,N-diisopropylethylamine (288 μl) and DMF (4 ml) was stirred at room temperature under a dry atmosphere (CaCl2 tube) for 1 h. The mixture was quenched with water and extracted with EtOAc. The organic layer was separated, washed with water and brine, dried over MgSO4 and concentrated in vacuo. The residue was dissolved in AcOH (4.0 ml) and stirred at 90° C. for 1 h. After AcOH was evaporated, the residue was purified by NH silica gel column chromatography (hexane/EtOAc). The resulting solid was recrystallized from EtOH to give the title compound (25.8 mg) as a pale yellow solid.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09365540B2
Source dataset	uspto-grants-2016_06
ORD ID	ord-a205f8d83f554a3dbde8083f00d82e2d
Source note	uspto-grants-2016_06