3-Chloro-4-fluoroaniline → 4-(3-Chloro-4-fluorophenylamino)-6-fluoro-1,7-naphthyridine-3-carbonitrile

HRID 2113561Notes

Reaction equation

HRID 2113561 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

4

Reactant 2

HCID 97083-Chloro-4-fluoroanilineHCID 185489604-Chloro-6-fluoro-1,7-naphthyridine-3-carbonitrile

Product 1

HCID 185489534-(3-Chloro-4-fluorophenylamino)-6-fluoro-1,7-naphthyridine-3-carbonitrileYield 99%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
140 °C

Procedure

In a microwave vial, 4-chloro-6-fluoro-1,7-naphthyridine-3-carbonitrile (1.25 g, 6.02 mmol, prepared as described in Wissner et. al., Bioorg. Med. Chem. Lett., 14, 2004, 1411-1416) and 3-chloro-4-fluoroaniline (0.96 g, 6.6 mmol) were taken up in DME. The vial was crimp-sealed and heated in a microwave reactor at 140° C. for 10 minutes. This was repeated with a second batch of reagents. The contents of the two vials were transferred together to a separatory funnel and partitioned between EtOAc and 5% Na2CO3, and the aqueous layer extracted two additional times with EtOAc. The combined organic extracts were washed with brine, dried over anhydrous MgSO4, 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 (3.78 g, 99% 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

  1. customThe vial was crimp-sealed
  2. customThe contents of the two vials were transferred together to a separatory funnel
  3. custompartitioned between EtOAc and 5% Na2CO3
  4. extractionthe aqueous layer extracted two additional times with EtOAc
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-73d84985410145778d5ccdaa50862fc1
Source dataset
uspto-grants-2008_10
Patent number
US07432279B2

Reaction notes

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