Hydrochloric Acid → HCID 131732649, compound

Participants

Reaction Conditions

Reaction Steps

To a flask charged with 4-((2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-N-(2-(dimethylamino)ethyl)benzamide (for a preparation see Intermediate 32) (197 mg, 0.5 mmol), sodium tert-butoxide (240 mg, 2.500 mmol), tris(dibenzylideneacetone)dipalladium(0) (229 mg, 0.250 mmol) and 2-(dimethylamino)-2′-(dicyclohexylphosphino)biphenyl (197 mg, 0.500 mmol) was added degassed toluene (4 mL). The resulting mixture was treated with 2-chloropyrazine (0.134 mL, 1.500 mmol) then stirred under nitrogen at 100° C. for ˜45 min. The mixture was cooled to room temperature and most of the solvent was evaporated in vacuo. The residue was partitioned between EtOAc and a saturated NaHCO3 solution and the layers were separated. The aqueous phase was extracted with EtOAc and the combined organic phases were washed with saturated aqueous NaHCO3 (×3), dried over MgSO4 and concentrated in vacuo. The residue was dissolved in DCM and loaded on a SCX column (20 g). The cartridge was eluted with DCM then with ammonia in MeOH (2N). The methanolic ammonia fractions were concentrated in vacuo and further purified by chromatography (25 g column, elution with 2N ammonia in MeOH/DCM gradient) to give a residue which was dissolved in 1,4-dioxane (4 ml). The solution was treated with hydrogen chloride in 1,4-dioxane (4N, 0.5 mL). The precipitate formed was isolated by filtration and dried at 60° C. under vacuum for 2 h to give 4-((2S,4R)-1-acetyl-2-methyl-4-(pyrimidin-2-ylamino)-1,2,3,4-tetrahydroquinolin-6-yl)-N-(2-(dimethylamino)ethyl)benzamide, Hydrochloride (93 mg, 0.183 mmol, 36.5% yield) as a white solid. LCMS (HpH, 2 min), Rt=0.79 min, MH+=473.

Provenance & Evidence