Cesium carbonate → 2-Bromo-6-(6-dimethylamino-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-4-fluoro-benzaldehyde

Participants

Role	Name	HCID	Charge
Reactant	Cesium carbonate	HCID 10796	—
Reactant	2,6-Dibromo-4-fluorobenzaldehyde	HCID 44474666	—
Reactant	6-(Dimethylamino)-3,4-dihydroisoquinolin-1(2H)-one	HCID 57424121	—
Catalyst	1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)	HCID 636044	—
Catalyst	(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium	HCID 6505921	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	2-Bromo-6-(6-dimethylamino-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-4-fluoro-benzaldehyde	HCID 59216535	48.9%

Reaction Steps

Combined 0.948 g (3.4 mmol, 2 eq) 2,6-Dibromo-4-fluoro-benzaldehyde, 0.320 g (1.7 mmol, 1 eq) 6-Dimethylamino-3,4-dihydro-2H-isoquinolin-1-one, 29 mg Xantphos (0.050 mmol, 0.03 eq), 19 mg bis(dibenzylideneacetone)palladium (0.033 mmol, 0.02 eq), and 1.09 g Cesium Carbonate (3 mmol, 2.0 eq) in 5 ml dioxane, bubbled argon gas through the mixture for 1 minute, sealed the reaction vessel and heated at 100 C for 3 hours, then cooled to 80 C and heated for 14 hours. Cooled, diluted ethyl acetate, washed water 2×, brine, dried mgso4. Rotovaped, chromatographed (10% to 30% ea in hexanes) to give a solid, 325 mg 2-Bromo-6-(6-dimethylamino-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-4-fluoro-benzaldehyde. MS (ESI) 391.0 (M+H)+.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07683064B2
Source dataset	uspto-grants-2010_03
ORD ID	ord-aeda26ced446470abf9a412b0293e603
Source note	uspto-grants-2010_03