N,N-Dimethylglycine → 4,5,6,7-Tetrahydrooxazolo[5,4-c]pyridine

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Reaction Conditions

Reaction Steps

Copper iodide (17 mg, 0.09 mmol) was added to a stirred suspension of {5-[(4-fluorophenyl)carbonyl]-4,5,6,7-tetrahydro[1,3]oxazolo[5,4-c]pyridin-2-yl}methanol (50 mg, 0.18 mmol), 2-bromo-4-methylpyridine (0.04 mL, 0.36 mmol), cesium carbonate (118 mg, 0.36 mmol) and N,N-dimethylglycine (18 mg, 0.18 mmol) in 1,4-dioxane (1 mL) in a sealed tube and under nitrogen. The mixture was stirred at 120° C. for 60 hours. The mixture was diluted with AcOEt and washed with a 16% aqueous solution of NH4OH. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; 7N solution of ammonia in MeOH in DCM 0/100 to 4/96). The desired fractions were collected and the solvents evaporated in vacuo. The crude product was purified by RP HPLC on (C18 XBridge 19×100 5 um). Mobile phase (Gradient from 80% 0.1% NH4CO3H/NH4OH pH 9 solution in Water, 20% ACN to 0% 0.1% NH4CO3H/NH4OH pH 9 solution in Water, 100% ACN). The solvents were evaporated in vacuo to yield 5-[(4-fluorophenyl)carbonyl]-2-1[(4-methylpyridin-2-yl)oxy]methyl}-4,5,6,7-tetrahydro[1,3]oxazolo[5,4-c]pyridine (6.7 mg, 10% yield) as a colourless oil. C20H18FN3O3 1H NMR (400 MHz, CDCl3) δ ppm 2.30 (s, 3 H), 2.72 (br. s., 2 H), 3.69 (br.s., 2 H), 4.75 (br. s., 2 H), 5.43 (s, 2 H), 6.65 (s, 1 H), 6.75 (d, J=5.1 Hz, 1 H), 7.13 (t, J=8.4 Hz, 2 H), 7.40-7.52 (m, 2 H), 8.01 (d, J=5.1 Hz, 1 H).

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