3-Iodopyridine → HCID 68184860, compound

Participants

Reaction Conditions

Reaction Steps

1,1-Dimethylethyl (2-{4-[(2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]-1H-pyrazol-1-yl}ethyl)methylcarbamate (for a preparation see intermediate 55) (150 mg, 0.351 mmol), 3-iodopyridine (144 mg, 0.702 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (DavePhos) (27.6 mg, 0.070 mmol), tris(dibenzylideneacetone)dipalladium(0) (32.1 mg, 0.035 mmol) and sodium tert-butoxide (67.4 mg, 0.702 mmol) were dissolved in 1,4-dioxane (4 mL) and the resulting mixture was stirred at 100° C. under nitrogen for 20 h, at 120° C. for 16 h, then cooled to room temperature and concentrated in vacuovacuo. The residue was partitioned between DCM and a saturated NaHCO3 aqueous solution and the layers were separated using a hydrophobic frit. The organic phase was concentrated in vacuovacuo. Purification of the residue by SP4 using a 50 G silica cartridge (gradient:0.5 to 10% (2M NH3 in MeOH) in DCM) gave 1,1-dimethylethyl (2-{4-[(2S,4R)-1-acetyl-2-methyl-4-(3-pyridinylamino)-1,2,3,4-tetrahydro-6-quinolinyl]-1H-pyrazol-1-yl}ethyl)methylcarbamate (84 mg, 0.166 mmol, 47.4% yield).

Provenance & Evidence