2-Chloro-3-methylpyridine → HCID 52936009, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (2S,4R)-1-acetyl-6-[1-(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)-1H-1,2,3-triazol-4-yl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinamine (for a preparation, see Intermediate 44) (31 mg, 0.072 mmol) and 2-chloro-3-methylpyridine (27.6 mg, 0.216 mmol) in toluene (2.5 mL) were successively added sodium tert-butoxide (69.3 mg, 0.722 mmol), tris(dibenzylideneacetone)dipalladium(0) (66.1 mg, 0.072 mmol) and 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (DavePhos) (56.8 mg, 0.144 mmol). The resulting mixture was stirred at 100° C. for 5 h then cooled to room temperature and filtered through Celite. The insoluble material was washed with 5% MeOH in DCM. The combined filtrate and washings were concentrated in vacuo and the residue was dissolved in a 1:1 (DMSO/MeOH) mixture and purified via MDAP (modifier: formic acid). The appropriate fractions were combined and were concentrated using a blow down apparatus (45° C.) to give 2-(4-{(2S,4R)-1-acetyl-2-methyl-4-[(3-methyl-2-pyridinyl)amino]-1,2,3,4-tetrahydro-6-quinolinyl}-1H-1,2,3-triazol-1-yl)ethanol (4.5 mg, 10.63 μmol, 15%) as viscous colourless oil.

Provenance & Evidence