Potassium Carbonate → 4-Methoxy-5''-methyl-6'-[2-(prop-1-yn-1-yl)pyridin-4-yl]-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazol]-4''-amine

Participants

Reaction Conditions

Reaction Steps

(1r,4r)-6′-Bromo-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2″-indene-1′,2″-imidazol]-4″-amine (Example 19, 75 mg, 0.20 mmol), potassium acetate (39.1 mg, 0.40 mmol), bis(pinacolato)diboron (55.7 mg, 0.22 mmol) and PdCl2(dppf)-CH2Cl2 adduct (8.14 mg, 9.97 μmol) were taken up in dioxane (2 mL) in a microwave vial. The reaction vessel was sealed and heated at 110° C. for 30 min and then at 120° C. for 15 min in a Biotage Initiator. After cooling, K2CO3 (55 mg, 0.40 mmol), Pd(Ph3P)4 (11.5 mg, 9.97 μmol), and water (0.3 mL) were added followed by 4-bromo-2-(prop-1-ynyl)pyridine (Intermediate 33, 39 mg, 0.20 mmol) in dioxane (1 mL). The reaction vessel was sealed and heated at 110° C. for 30 min in a Biotage Initiator. After cooling, the mixture was filtered and concentrated in vacuo. The product was purified by flash chromatography using a gradient of EtOAc in heptane (0-100%), then EtOAc:MeOH (9:1) followed by preparative chromatography to give the title compound (7 mg, 9% yield): 1H NMR (500 MHz, DMSO-d6) δ ppm 0.96 (m, 1 H), 1.12-1.29 (m, 2 H), 1.39-1.50 (m, 3 H), 1.83 (m, 2 H), 2.08 (s, 3 H), 2.18 (s, 3 H), 2.90-3.13 (m, 3 H), 3.20 (s, 3 H), 6.56 (s, 2 H), 6.89 (d, 1 H), 7.42 (d, 1 H), 7.50 (dd, 1 H), 7.58 (d, 1 H), 7.62 (dd, 1 H), 8.49 (d, 1 H); MS (MM−ES+APCI)+m/z 413 [M+H]+.

Provenance & Evidence