2-Methyltetrahydrofuran → 7'-(5-Chloropyridin-3-yl)-5-methyl-3',4'-dihydro-2'H-spiro[imidazole-2,1'-naphthalen]-4-amine

Participants

Reaction Conditions

Reaction Steps

Sodium tetrachloropalladate(II) (3.52 mg, 0.01 mmol), 3-(di-tert-butylphosphonium)propane sulfonate (6.43 mg, 0.02 mmol), 5-chloropyridin-3-ylboronic acid (51.6 mg, 0.31 mmol) and 7′-bromo-5-methyl-3′,4′-dihydro-2′H-spiro[imidazole-2,1′-naphthalen]-4-amine (Example 51 Step 4, 70 mg, 0.24 mmol) were added to a vial. 2-Methyl-tetrahydrofuran (1 mL) and K2CO3 (2M aq.) (0.359 mL, 0.72 mmol) were added and the mixture was degassed by bubbling N2 (g). The vial was sealed and heated in a microwave reactor at 90° C. for 30 min. EtOAc (5 mL) and water (5 mL) were added and the phases were separated. The aqueous phase was extracted with EtOAc twice and the combined organic layers were dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography (4 g SiO2, O-10% MeOH containing 0.1M NH3 in DCM). The fractions containing product were combined and concentrated, yielding the title compound (26 mg, 33% yield). 1H NMR (500 MHz, CD3OD) δ ppm 1.85-1.94 (m, 1 H), 2.01 (ddd, 1 H), 2.08-2.17 (m, 1 H), 2.17-2.27 (m, 1 H), 2.35 (s, 3 H), 3.02 (t, 2 H), 6.84 (d, 1 H), 7.34 (d, 1 H), 7.48 (dd, 1 H), 7.97 (t, 1 H), 8.48 (d, 1 H), 8.57 (d, 1 H); MS (ES+) m/z 325 [M+H]+.

Provenance & Evidence