Diisopropylethylamine → 6-(1-Methyl-1H-1,2,3-triazol-5-yl)-3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

Temperature

100 °C

A degassed mixture of 6-iodo-3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (100 mg, 0.21 mmol), 1-methyl-5-(trimethylstannyl)-1H-1,2,3-triazole (158 mg, 0.64 mmol) and bis(triphenylphosphine)palladium(II) dichloride (15 mg, 0.021 mmol) in N,N-diisopropylethylamine (0.74 mL, 0.43 mmol) in 1,4-dioxane (1.7 mL) was heated at 100° C. for 1 h. The cooled reaction mixture was diluted with DCM (20 mL) and methanol (2 mL) and washed with water (15 mL). The organic phase was separated, dried over sodium sulfate, filtered and evaporated in vacuo to afford a residue that was purified by preparative HPLC (20-60% MeCN in water (0.1% ammonium hydroxide) over 30 min, 35 mL/min) to afford the title compound as a pale yellow solid (20 mg, 20%). 1H NMR (DMSO-D6, 400 MHz): 12.47 (s, 1H), 9.05 (s, 1H), 9.04 (d, J=2.2 Hz, 1H), 8.96 (d, J=2.2 Hz, 1H), 8.78 (s, 1H), 8.18 (s, 1H), 7.77 (d, J=8.1 Hz, 2H), 7.45 (d, J=8.1 Hz, 2H), 4.37 (s, 3H), 3.50 (s, 2H), 2.35 (s, 4H), 1.52 (m, 4H), 1.41 (m, 2H). LCMS (method D): RT=8.04 min, M+H+=424.

1. customThe cooled reaction mixture
2. washwashed with water (15 mL)
3. customThe organic phase was separated
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. customevaporated in vacuo
7. customto afford a residue that
8. customwas purified by preparative HPLC (20-60% MeCN in water (0.1% ammonium hydroxide) over 30 min, 35 mL/min)

ORD record

ord-36023edd53eb4cdfab0a640405e08e36

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09216980B2