Triethylamine → 2-chloro-1-(3-(4-methoxybenzyl)-8,9-dihydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-7(6H)-yl)-2-phenylethanone

To a solution of 3-(4-methoxybenzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridine (1.536 g, 5.22 mmol) in anhydrous dichloromethane (20 mL) was added triethylamine (2.18 mL, 15.66 mmol) followed by 2-chloro-2-phenylacetyl chloride (90%, 1.05 mL, 6.52 mmol). The mixture was stirred at room temperature for 1 hour. The reaction was quenched by the addition of water (10 mL). The reaction mixture was extracted with dichloromethane (10 mL) and the organic layer washed with brine (2×10 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to give the crude product. The crude product was purified by flash column chromatography (SiO2, gradient from 40% EtOAc in hexanes to 50% EtOAc in hexanes) to give the desired product, 2-chloro-1-(3-(4-methoxybenzyl)-8,9-dihydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-7(6H)-yl)-2-phenylethanone as an off-white solid (1.99 g, 85%). 1H NMR (400 MHz, DMSO-d6) δ 8.43/8.24 (s, 1H, rotamers), 8.15/8.12 (s, 1H, rotamers), 7.52 (m, 2H), 7.40 (m, 3H), 7.17 (m, 2H), 6.83 (m, 2H), 6.53/6.48 (s, 1H, rotamers), 5.56 (s, 2H), 5.02-4.70 (m, 2H), 3.84 (m, 2H), 3.68 (s, 3H), 3.11/2.67 (m, 2H, rotamers); LCMS [M+H]: 447.

1. customThe reaction was quenched by the addition of water (10 mL)
2. extractionThe reaction mixture was extracted with dichloromethane (10 mL)
3. washthe organic layer washed with brine (2×10 mL)
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customto give the crude product
8. customThe crude product was purified by flash column chromatography (SiO2, gradient from 40% EtOAc in hexanes to 50% EtOAc in hexanes)

ORD record

ord-3ac243411d524104a9d1a22a900d4030

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08263610B2