Diisopropylethylamine → 2-Methyl-2-[4-(2-pyridin-2-yl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl)piperidin-1-yl]propionic acid methyl ester

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)	HCID 636044	—
Reactant	9-Bromo-2-pyridin-2-yl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene	HCID 68312700	—
Reactant	2-(4-Mercaptopiperidin-1-yl)-2-methylpropionic acid methyl ester	HCID 86671453	—
Catalyst	Bis(dibenzylideneacetone)palladium	HCID 9811564	—
Solvent	Dichloromethane	HCID 6344	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	2-Methyl-2-[4-(2-pyridin-2-yl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl)piperidin-1-yl]propionic acid methyl ester	HCID 68312704	—

Reaction Conditions

Temperature	120 °C

Reaction Steps

A mixture of 9-bromo-2-pyridin-2-yl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (300 mg, 0.877 mmol), 2-(4-mercaptopiperidin-1-yl)-2-methylpropionic acid methyl ester (286 mg, 1.315 mmol), Pd2(dba)3 (40 mg, 5 mol %), XantPhos (51 mg, 10 mol %) and DIPEA (0.61 mL, 3.5 mmol) in dioxane (10 mL) was purged with nitrogen and then heated at 120° C. for 1 h using microwave irradiation. The crude reaction mixture was diluted with DCM (150 mL) and purified by column chromatography (Si-PCC, gradient 0-8% 2M NH3/MeOH in DCM) affording 2-Methyl-2-[4-(2-pyridin-2-yl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl)piperidin-1-yl]propionic acid methyl ester as an orange oil (0.674 g, quantitative). LCMS: RT1.88 min [M+H]+ 479.1.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09090628B2
Source dataset	uspto-grants-2015_07
ORD ID	ord-7207fe587d874af1ab60e507c0fba4e4
Source note	uspto-grants-2015_07