Dimethylformamide → 5-Fluoro-6-methoxy-8-oxo-5,6,7,8-tetrahydro-1,7-naphthyridine-3-carbonitrile
Reaction equation
COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.Cl[C:31]1[CH:32]=[N:33][C:34]2[C:35](=[O:44])[NH:36][CH:37]([O:42][CH3:43])[CH:38]([F:41])[C:39]=2[CH:40]=1.[CH3:45][N:46](C=O)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:41][CH:38]1[CH:37]([O:42][CH3:43])[NH:36][C:35](=[O:44])[C:34]2[N:33]=[CH:32][C:31]([C:45]#[N:46])=[CH:40][C:39]1=2Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 110 °C
Procedure
A pressure bottle was charged with Pd2 dba3 (1.032 g, 1.127 mmol), S-Phos (1.157 g, 2.82 mmol), ZnCN2 (2.482 g, 21.14 mmol), 3-chloro-5-fluoro-6-methoxy-6,7-dihydro-1,7-naphthyridin-8(5H)-one (3.25 g, 14.09 mmol) and DMF (70.5 ml). The bottle was purged with argon and sealed, and the reaction mixture was heated at 110° C. for 1 h. Upon cooling to RT the crude reaction mixture was filtered through Celite and washed with MeOH. The filtrate was concentrated. The crude solids were triturated with DCM, filtered, washed with DCM and air-dried. 5-fluoro-6-methoxy-8-oxo-5,6,7,8-tetrahydro-1,7-naphthyridine-3-carbonitrile (2.27 g, 10.26 mmol, 72.8% yield) was isolated as an off white solid. LC/MS (ESI+) m/z=222.0 (M+H).
Workup
- customThe bottle was purged with argon
- customsealed
- temperatureUpon cooling to RT the crude
- customreaction mixture
- filtrationwas filtered through Celite
- washwashed with MeOH
- concentrationThe filtrate was concentrated
- customThe crude solids were triturated with DCM
- filtrationfiltered
- washwashed with DCM
- customair-dried
Sources & evidence
- ORD record
- ord-eef7e583e7484870ad0cad26924b982d
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09309263B2
Reaction notes
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