2-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl → 6-morpholin-4-ylbenzo[d]isothiazole-3-carboxylic acid ((3R)-1-azabicyclo[2.2.2]oct-3-yl)amide

In a 5 mL microwave reaction vessel was added N-((3R)-1-azabicyclo[2.2.2]oct-3-yl)-5-(bromo)benzo[d]isothiazole-3-carboxamide (133 mg, 0.37 mmol), tris(dibenzylideneacetone)dipalladium (0) (34 mg, 0.04 mmol), caesium bicarbonate (213 mg, 1.1 mmol), and (2′-dicyclohexylphosphanylbiphenyl-2-yl)dimethylamine (30 mg, 0.07 mmol). The vial was then evacuated and back-filled with argon gas. The mixture of solids was then diluted with morpholine (0.7 mL), dioxane (1 mL), and triethylamine (0.5 mL) and the reaction vessel was sealed. The reaction mixture was subjected to microwave irradiation at 120° C. for 1800 s. The reaction mixture was filtered through a plug of celite and concentrated in vacuo. The crude product was purified by chromatography (90/10/1 dichloromethane/methanol/ammonium hydroxide) to provide 47 mg (34%) of 6-morpholin-4-ylbenzo[d]isothiazole-3-carboxylic acid ((3R)-1-azabicyclo[2.2.2]oct-3-yl)amide as a colorless solid.

1. customThe vial was then evacuated
2. additionback-filled with argon gas
3. additionThe mixture of solids
4. additionwas then diluted with morpholine (0.7 mL), dioxane (1 mL), and triethylamine (0.5 mL)
5. customthe reaction vessel was sealed
6. customirradiation at 120° C. for 1800 s
7. filtrationThe reaction mixture was filtered through a plug of celite and
8. concentrationconcentrated in vacuo
9. customThe crude product was purified by chromatography (90/10/1 dichloromethane/methanol/ammonium hydroxide)

ORD record

ord-5b8eef39b7e94748a68be248fda01dbb

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08252811B2