Bis(2-chloroethyl) ether → 1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one

Temperature

150 °C

A suspension of 2-(3-((cis-3-aminocyclobutyl)amino)-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one hydrochloride (Example 435; 26.0 mg, 0.065 mmol), bis(2-chloroethyl) ether (Aldrich; 0.015 mL, 0.130 mmol), and DIPEA (0.068 mL, 0.391 mmol) in DMF (1.0 mL) was stirred in a sealed flask at 150° C. for 70 min. The reaction mixture was then concentrated onto silica gel and chromatographically purified (silica gel, 0-10% (2M NH3 in MeOH)/DCM). Product-containing fractions were combined and diluted with DCM (20 mL), and the resulting mixture was sequentially washed with half-saturated brine (30 mL) and water (30 mL), dried over Na2SO4, filtered, and concentrated in vacuo to provide 2-(2-methyl-3-((1s,3s)-3-morpholinocyclobutyl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (5.8 mg, 0.013 mmol, 21% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 12.63 (1H, br. s.), 7.95 (1H, dd, J=7.5, 1.3 Hz), 7.68 (1H, dd, J=8.1, 1.3 Hz), 7.41 (1H, t, J=7.8 Hz), 7.14 (1H, d, J=2.0 Hz), 5.25-5.33 (1H, m), 5.09 (1H, d, J=4.1 Hz), 4.22-4.32 (1H, m), 3.75 (4H, t, J=4.5 Hz), 3.70 (2H, m, J=6.8, 6.8, 2.5 Hz), 3.61-3.67 (1H, m), 3.00 (2H, t, J=6.8 Hz), 2.82-2.92 (2H, m), 2.57 (3H, s), 2.42 (4H, br. s.), 1.90-2.01 (2H, m). m/z (ESI, +ve) 433.1 (M+H)+.

1. concentrationThe reaction mixture was then concentrated onto silica gel
2. customchromatographically purified (silica gel, 0-10% (2M NH3 in MeOH)/DCM)
3. additiondiluted with DCM (20 mL)
4. washthe resulting mixture was sequentially washed with half-saturated brine (30 mL) and water (30 mL)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo

ORD record

ord-68680ce045c641de9a60147ffc629e79

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394297B2