Dimethylformamide → 5-Fluoro-6-methoxy-8-oxo-5,6,7,8-tetrahydro-1,7-naphthyridine-3-carbonitrile

Temperature

110 °C

A pressure bottle was charged with Pd(dba)3 (Strem, 1.032 g, 1.127 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (Strem 1.157 g, 2.82 mmol), zinc cyanide (Alfa Aesar, 2.482 g, 21.14 mmol), 3-chloro-5-fluoro-6-methoxy-6,7-dihydro-1,7-naphthyridin-8(5H)-one (step 1, 3.25 g, 14.09 mmol) and DMF (70 ml). The bottle was purged with Argon and the reaction mixture was heated to 110° C. for 1 h. The crude reaction mixture was filtered through a pad of Celite and the filtercake was washed with MeOH. The combined filtrates were concentrated under reduced pressure. The residue was triturated with DCM. The solid was filtered off and washed with DCM. The title compound (2.27 g, 10.26 mmol, 72.8% yield) was obtained as an off white solid. MS m/z=222 [M+H]+. Calculated for C10H8FN3O2: 221.1

1. customThe bottle was purged with Argon
2. customThe crude reaction mixture
3. filtrationwas filtered through a pad of Celite
4. washthe filtercake was washed with MeOH
5. concentrationThe combined filtrates were concentrated under reduced pressure
6. customThe residue was triturated with DCM
7. filtrationThe solid was filtered off
8. washwashed with DCM

ORD record

ord-e138b66f51d04b9c8cafec73c6b592e3

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296734B2