2-Aminothiazole → (S)-2-(2-(difluoromethyl)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)-N-(3H-pyrrol-2-yl)-1H-benzo[d]imidazole-4-carboxamide

Participants

Role	Name	HCID	Charge
Reactant	2-Aminothiazole	HCID 2155	—
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	(S)-2-(2-(difluoromethyl)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)-1H-benzo[d]imidazole-4-carboxylic acid	HCID 67202420	—
Solvent	Water	HCID 962	—
Solvent	Dimethylformamide	HCID 6228	—
Product	(S)-2-(2-(difluoromethyl)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)-N-(3H-pyrrol-2-yl)-1H-benzo[d]imidazole-4-carboxamide	HCID 86653796	66.8%

Reaction Steps

(S)-2-(2-(difluoromethyl)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)-1H-benzo[d]imidazole-4-carboxylic acid (67; 100 mg, 0.239 mmol) was taken up in 10 ml of DMF along with 2-aminothiazole (4; 28.7 mg, 0.289 mmol), HATU (181.7 mg, 0.478 mmol) and DIEA (61.8 mg, 0.289 mmol). The resulting reaction mixture was stirred at room temperature for 12 h and diluted with water. The precipitated solids were collected by filtration and dried. Purification by chromatography (EtOAc/Hexane=2:1) afforded (S)-2-(2-(difluoromethyl)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)-N-(thiazol-2-yl)-1H-benzo[d]imidazole-4-carboxamide 68 (77 mg, 65%). MS (ESI) calcd for C24H22F2N4O4S: 500.13; found: 501 [M+H].

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08846947B2
Source dataset	uspto-grants-2014_09
ORD ID	ord-dd269dcac0504a0595b29b92d5b69e85
Source note	uspto-grants-2014_09