Cesium carbonate → (R)-N-(6-(methylthio)thiazolo[5,4-b]pyrazin-2-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octan]-2-amine

Participants

Reaction Conditions

Reaction Steps

A mixture of dimethyl 6-bromothiazolo[5,4-b]pyrazin-2-ylcarbonimidodithioate from Step A of Example 263 (100 mg, 0.298 mmol), (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (68 mg, 0.298 mmol) and cesium carbonate (100 mg, 0.60 mmol) in DMF (1.5 mL) was placed in a 1 dram vial and heated on a 100° C. oil bath for 1 hour, at which time, sodium thiomethoxide (100 mg, 1.43 mmol) was added and the mixture was heated overnight. The mixture was cooled to ambient temperature and poured into water (20 mL) and the resulting solids were collected by filtration and then purified by silica gel chromatography (2-40% 9:1 methanol:ammonium hydroxide-chloroform). The product fractions were combined and concentrated in vacuo to afford (R)—N-(6-(methylthio)thiazolo[5,4-b]pyrazin-2-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (52 mg, 46% yield). 1H NMR (500 MHz, CDCl3) δ ppm 9.39 (br. s., 1 H) 8.31 (s, 1 H) 4.03 (d, J=9.77 Hz, 1 H) 3.70 (d, J=9.77 Hz, 1 H) 3.41 (dd, J=14.95, 1.83 Hz, 1 H) 2.73-3.10 (m, 5 H) 2.63 (s, 3 H) 2.10-2.25 (m, 2 H) 1.47-1.86 (m, 3 H). MS (LC/MS) R.T.=1.04; [M+H]+=363.04.

Provenance & Evidence