Diisopropylethylamine → 6-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-N-methyl-N-((2R,3S,4S,5S)-2,3,4,5,6-pentakis(tert-butyldimethyl silyloxy)hexyl)nicotinamide

Participants

Role	Name	HCID	Charge
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	6-(7-(4-(3-Cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)nicotinic acid	HCID 67441828	—
Reactant	(2R,3S,4S,5S)-2,3,4,5,6-pentakis(tert-butyldimethylsilyloxy)-N-methylhexan-1-amine	HCID 86658595	—
Solvent	Dimethylformamide	HCID 6228	—
Product	6-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-N-methyl-N-((2R,3S,4S,5S)-2,3,4,5,6-pentakis(tert-butyldimethyl silyloxy)hexyl)nicotinamide	HCID 86658594	54%

Reaction Steps

To a solution of acid 225 (220 mg, 0.474 mmol, scheme 54), amine 242 (309 mg, 0.474 mmol) and DIPEA (0.331 mL, 1.895 mmol) in DMF (5 mL) was added HATU reagent (270 mg, 0.710 mmol). The mixture was stirred overnight at room temperature then partitioned between ethyl acetate and water. The organic layer was collected, washed with water, 1M NaOH, and brine, dried over anhydrous MgSO4, filtered and concentrated. The residue was purified by Biotage (MeOH/DCM, 0-15%, SNAP 10 g cartridge) to afford title compound 243 (250 mg, 0.254 mmol, 54% yield) as a white solid. MS: 985.4 (MH+).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08906852B2
Source dataset	uspto-grants-2014_12
ORD ID	ord-4619f488fb9d49ce96922983cd05f57e
Source note	uspto-grants-2014_12