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-b47c5cd4977d4fe7b2c3dc931cf1725b

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09085576B2