Sodium Carbonate → HCID 135965689, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of tert-butyl 4-(5-(4-(butyloxycarbonylaminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)-2-bromothiazol-5-ylcarbamate (0.123 g, 0.20 mmol), Na2CO3 (42 mg, 0.40 mmol) and 4-hydroxy-2-(trifluoromethyl)benzeneboronic acid (66 mg, 0.32 mmol) in DME (1.5 mL) and water (0.5 mL) was degassed by gently bubbling nitrogen through the mixture for 15 min. [1,1′-Bis(diphenylphosphino)ferrocene]dichloro-palladium(II) (16 mg, 0.02 mmol) was then added and the mixture degassed for a further 10 min before being heated in a microwave at 130° C. for 40 min. The solvents were removed under reduced pressure and the residue purified via silica gel column chromatography (0-100% EtOAc/isohexane). The isolated intermediate was dissolved in a solution of HCl in 1,4-dioxane (4 M, 2 mL) and stirred at room temperature for 16 hr. The solvent was removed under reduced pressure and the residue purified by preparative HPLC to yield 278 as a pale brown solid (48 mg, 48%). 1H NMR (400 MHz, d4-MeOD) δ 7.59 (s, 1H), 7.44 (d, J=8.5 Hz, 1H), 7.15 (d, J=2.5 Hz, 1H), 6.98 (dd, J=8.5, 2.5 Hz, 1H), 3.72 (s, 3H), 3.22-3.10 (m, 4H), 2.71 (d, J=6.8 Hz, 2H), 1.85 (d, J=12.6 Hz, 2H), 1.66-1.55 (m, 1H), 1.47-1.33 (m, 2H). LCMS (ES+) m/z 496 (M+1).

Provenance & Evidence