Diisopropylethylamine → (S)-tert-butyl 1-(((2-(7-(4-(3-(2,4-difluorophenyl)ureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1-methyl-1H-imidazol-5-yl)methyl)(2-methoxyethyl)amino)-3-methyl-1-oxobutan-2-ylcarbamate

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Boc-L-Valine	HCID 83693	—
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-(2,4-difluorophenyl)-3-(3-fluoro-4-(2-(5-((2-methoxyethylamino)methyl)-1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)urea	HCID 57919488	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	(S)-tert-butyl 1-(((2-(7-(4-(3-(2,4-difluorophenyl)ureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1-methyl-1H-imidazol-5-yl)methyl)(2-methoxyethyl)amino)-3-methyl-1-oxobutan-2-ylcarbamate	HCID 67048306	53.2%

Reaction Steps

To a solution of the compound 351 (280 mg, 0.481 mmol) in DMF (10 ml) was added (S)-2-(tert-butoxycarbonylamino)-3-methylbutanoic acid (209 mg, 2 eq, 0.961 mmol), iPr2NEt (0.252 ml, 3 eq, 0.1.442 mmol) and HATU (365 mg, 2 eq, 0.961 mmol) and the reaction mixture was stirred overnight. The reaction mixture was diluted with EtOAc and washed with water, saturated NAHCO3 solution then brine. The organic phase was collected, dried over Na2SO4, filtered then concentrated. Purification of the residue by column chromatography (eluent 20% MeOH in EtOAc) afforded the desired compound 352 as an off-white solid (200 mg, 53% yield). MS (m/z)=782.7 (M+H).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08729268B2
Source dataset	uspto-grants-2014_05
ORD ID	ord-87a6a632b68c4ff090b0eaf2d7d80bad
Source note	uspto-grants-2014_05