Potassium Phosphate, Tribasic → 3-chloro-5-{1-[(3-methyl phenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-4-pyridinecarbonitrile

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Reaction Conditions

Reaction Steps

A mixture of 3,5-dichloro-4-pyridinecarbonitrile (400 mg, 2.312 mmol), 1-[(3-methylphenyl)acetyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole (872 mg, 2.312 mmol), Pd2(dba)3 (42.3 mg, 0.046 mmol) and K3PO4 (982 mg, 4.62 mmol) in 9 mL of dioxane and 3 mL of water in a microwave tube was degassed and backflushed with nitrogen, followed by addition of tri-(t-butyl)phosphonium tetrafluoroborate salt (26.8 mg, 0.092 mmol). The mixture was degassed and backflushed with nitrogen. The mixture was heated in a microwave reactor at 120° C. for 40 minutes. LCMS showed there was no stating material. The mixture was cooled to room temperature, and the mixture was filtered. The filtered solid was purified by silica gel column chromatography on a silica gel cartridge using gradient elution of 100% CH2Cl2 to 90:10:1 CH2Cl2/CH3OH/NH3OH. The combined product fractions were evaporated to dryness to give 3-chloro-5-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-4-pyridinecarbonitrile as a pale yellow solid (255 mg, 26% yield). LCMS [M+1] 388. 1H NMR (400 MHz, DMSO-d6) δ 2.31 (s, 3H), 3.24 (t, J=8.34 Hz, 2H), 3.85 (s, 2H), 4.25 (t, J=8.46 Hz, 2H), 7.06-7.14 (m, 3H), 7.20-7.27 (m, 1H), 7.51 (d, J=8.34, 1H), 7.58 (s, 1H), 8.21 (d, J=8.34 Hz, 1H), 8.82 (s, 1H), 8.93 (s, 1H).

Provenance & Evidence