Diisopropylethylamine → N-(3-Chloro-4-fluoro-phenyl)-2-{2,6-dichloro-3-[(2-fluoro-2-methyl-propionylamino)-methyl]-phenylamino}-6-(2,2-difluoroethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid amide

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate	HCID 2733207	—
Reactant	2-Fluoro-2-methylpropanoic acid	HCID 2782828	—
Reactant	N-(3-Chloro-4-fluoro-phenyl)-2-(2,6-dichloro-3-aminomethyl-phenylamino)-6-(2,2-difluoroethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid amide	HCID 86669639	—
Solvent	Dimethylformamide	HCID 6228	—
Product	N-(3-Chloro-4-fluoro-phenyl)-2-{2,6-dichloro-3-[(2-fluoro-2-methyl-propionylamino)-methyl]-phenylamino}-6-(2,2-difluoroethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid amide	HCID 86669640	—

Reaction Steps

TBTU (1.0 mL of a 0.11 M solution in DMF) was added to a mixture of N-(3-chloro-4-fluoro-phenyl)-2-(2,6-dichloro-3-aminomethyl-phenylamino)-6-(2,2-difluoroethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid amide (1.0 mL of a 0.10 M solution in DMF), DIPEA (52 μl, 0.3 mmol) and 2-fluoro-2-methylpropionic acid (1.0 mL of a 0.13 M solution in DMF) and it was stirred for 3 d and the mixture was purified by prep. HPLC.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08759537B2
Source dataset	uspto-grants-2014_06
ORD ID	ord-1ebd60b54b654ef98fd4eca3d1eb8ddb
Source note	uspto-grants-2014_06