Potassium Carbonate → 3-(4''-Amino-5''-methyl-3'H-dispiro[cyclopropane-1,2'-indene-1',2''-imidazol]-6'-yl)-5-chlorobenzonitrile

Participants

Reaction Conditions

Reaction Steps

6′-Bromo-5″-methyl-3′H-dispiro[cyclopropane-1,2′-indene-1′,2″-imidazol]-4″-amine (Example 77, 0.10 g, 0.33 mmol), 3-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (Intermediate 35, 0.121 g, 0.46 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride (0.048 g, 0.07 mmol), 2 M aq. K2CO3 (0.493 mL, 0.99 mmol) and THF (1 mL) were added to microwave vial. The mixture was degassed by bubbling N2 (g) through it. The vial was sealed and heated in a microwave reactor at 130° C. for 30 min. [1,1′-Bis(diphenylphosphino)-ferrocene]palladium(II) chloride (0.048 g, 0.07 mmol) was added and the mixture was degassed by bubbling N2 (g) through it. The vial was sealed and heated in a microwave reactor at 130° C. for 30 min. The residue was dissolved in EtOAc and the mixture was extracted with 1.0 M HCl (2×10 mL). The organic layer was discarded while the aq phase was basified to pH 12 by addition of 1 M NaOH (aq). The basic water phase was extracted with DCM (2×20 mL). The organic phase was dried through a phase separator and concentrated in vacuo. The crude product was purified by flash chromatography (0-10% 0.1 M NH3 in McOH, in DCM, 25 g SiO2 column). The product was purified by a second flash chromatography (0-100% EtOAc in heptane, 25 g SiO2 column) followed by preparative chromatography. The fractions containing pure product were combined and concentrated. DCM was added and the organic phase was collected and dried through a phase separator and concentrated in vacuo, yielding the title compound (10 mg, 0.028 mmol, 8% yield): 1H NMR (500 MHz, CD3OD) δ ppm 0.14-0.23 (m, 1H), 0.50-0.58 (m, 1H), 0.62-0.70 (m, 1H), 0.80 (ddd, 1H), 2.30 (s, 3H), 2.96 (d, 1H), 3.49 (d, 1H), 7.02-7.08 (m, 1H), 7.47 (d, 1H), 7.59 (dd, 1H), 7.73 (s, 1H), 7.88 (s, 2H); MS (MM-ES+APCI)+ m/z 361 [M+H]+.

Provenance & Evidence