3-Chloro-4-fluoroaniline → 4-(3-Chloro-4-fluorophenylamino)-6-fluoro-1,7-naphthyridine-3-carbonitrile
Reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][N:8]=[C:9]([F:12])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:13]#[N:14].[Cl:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][C:22]=1[F:23])[NH2:19]>COCCOC>[Cl:15][C:16]1[CH:17]=[C:18]([NH:19][C:2]2[C:11]3[C:6](=[CH:7][N:8]=[C:9]([F:12])[CH:10]=3)[N:5]=[CH:4][C:3]=2[C:13]#[N:14])[CH:20]=[CH:21][C:22]=1[F:23]Participants
Conditions
- Temperature
- 140 °C
Procedure
In a microwave vial, 4-chloro-6-fluoro-1,7-naphthyridine-3-carbonitrile (1.3 g, 6.3 mmol) and 3-chloro-4-fluoroaniline (1.0 g, 6.9 mmol) were taken up in DME. The vial was crimp-sealed and heated in a microwave reactor at 140° C. for 15 minutes. This was repeated with another two batches of reagents. The contents of the three vials were transferred together to a separatory funnel and partitioned between EtOAc and 10% Na2CO3, and the aqueous layer extracted two additional times with EtOAc. The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, filtered and evaporated to give 4-(3-chloro-4-fluorophenylamino)-6-fluoro-1,7-naphthyridine-3-carbonitrile of sufficient purity to be used directly in the next step (4.6 g, 75.3% yield): 1H NMR (400 MHz, DMSO-D6) δ 7.32-7.49 (m, 1 H) 7.53 (t, J=9.0 Hz, 1 H) 7.72 (dd, J=6.3, 2.3 Hz, 1 H) 8.16 (s, 1 H) 8.69 (s, 1 H) 9.08 (s, 1 H) 10.14 (s, 1 H).
Workup
- customThe vial was crimp-sealed
- customThe contents of the three vials were transferred together to a separatory funnel
- custompartitioned between EtOAc and 10% Na2CO3
- extractionthe aqueous layer extracted two additional times with EtOAc
- washThe combined organic extracts were washed with brine
- dry with materialdried over anhydrous Na2SO4
- filtrationfiltered
- customevaporated
Sources & evidence
- ORD record
- ord-7104d609c8ca4bfd9f7f5c3f14f683ab
- Source dataset
- uspto-grants-2008_10
- Patent number
- US07432279B2
Reaction notes
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