2-Aminothiazole → (6-(Thiazol-2-ylamino)pyridine-3-yl)methanol

Participants

Reaction Conditions

Reaction Steps

A suspension of (6-chloropyridin-3-yl)methanol (11.23 g, 78.22 mmol), 2-aminothiazole (9.40 g, 93.86 mmol, 1.2 eq), sodium carbonate (11.6 g, 109.5 mol, 1.4 eq) and XANTPHOS (0.543 g, 0.939 mmol, 0.012 eq) in THF (60 mL, bubbled with argon for 5 minutes) was bubbled again with argon for 5 additional minutes. Tris(dibenzylideneacetone)dipalladium (0) (0.269 g, 0.293 mmol, 0.004 eq) was then added to the suspension which was heated at 120° C. for 4 days. The mixture was cooled down to RT and filtered. The resulting solid was washed with toluene and tetrahydrofuran and suspended in water. This suspension was stirred for ˜0.5 hour and then filtered. The resulting solid was dried overnight under vacuum to give the title material (15.072 g, 93%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 4.44 (2H, d, J=5.6 Hz), 5.16 (1H, t, J=5.6 Hz), 6.98 (1H, d, J=3.7 Hz), 7.04 (1H, d, J=8.5 Hz), 7.37 (1H, d, J=3.6 Hz), 7.66 (1H, dd, J=8.5 and 2.2 Hz), 8.21 (1H, br d, J=1.5 Hz), 11.22 (1H, s). LC/MS (M+H)+: 208. HPLC ret. time (Condition A): 0.375 min.

Provenance & Evidence