Diisopropylethylamine → 1-{[4-[2-(3-Fluoro-phenyl)-7-methoxy-8-methyl-quinazolin-4-yloxy]-2-(hex-5-enyl-methyl-carbamoyl)-cyclopentanecarbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester

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	2-(1-Ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-4-[2-(3-fluoro-phenyl)-7-methoxy-8-methyl-quinazolin-4-yloxy]-cyclopentanecarboxylic acid	HCID 68686580	—
Reactant	N-Methylhex-5-en-1-amine hydrochloride	HCID 71413963	—
Solvent	Dimethylformamide	HCID 6228	—
Product	1-{[4-[2-(3-Fluoro-phenyl)-7-methoxy-8-methyl-quinazolin-4-yloxy]-2-(hex-5-enyl-methyl-carbamoyl)-cyclopentanecarbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester	HCID 68412435	76%

Reaction Steps

Compound 156 (0.81 g, 1.40 mmol) and hex-5-enyl-methyl-amine hydrochloride (272 mg, 1.82 mmol) was dissolved in dry DMF (50 mL). DIEA (975 μL, 5.6 mmol) was added and the reaction flask was placed in an ice bath. After 10 minutes HATU (559 mg, 1.47 mmol) was added to the solution. The reaction flask was allowed to reach room temperature and the stirring was continued for 3 hrs before the solvent was removed by evaporation. The crude product was extracted with CHCl3 and washed with saturated NaHCO3 (aq). The organic phase was dried (Na2SO4), evaporated on silica and purified to by flash chromatography (heptane:ethyl acetate 1:1) to give the title compound (0.716 g, 76%), LRMS (M+H) 673.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07659245B2
Source dataset	uspto-grants-2010_02
ORD ID	ord-9ee09cd385e049b09a27f5c90dfce346
Source note	uspto-grants-2010_02