Dimethylformamide → 4-Chloro-6-fluoro-1,7-naphthyridine-3-carbonitrile

HRID 276854ノート

反応式

HRID 276854 の反応式
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2O.C(Cl)(=O)C([Cl:18])=O.CN(C)C=O.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl>[Cl:18][C:5]1[C:4]2[C:9](=[CH:10][N:11]=[C:2]([F:1])[CH:3]=2)[N:8]=[CH:7][C:6]=1[C:12]#[N:13]

参加物

6

反応物 4

HCID 6228Dimethylformamide2 回HCID 11430Potassium CarbonateHCID 65578Oxalyl chloride2 回HCID 1785103236-Fluoro-4-hydroxy-1,7-naphthyridine-3-carbonitrile

生成物 1

HCID 185489604-Chloro-6-fluoro-1,7-naphthyridine-3-carbonitrile収率 92%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To 10 g of 6-fluoro-4-hydroxy-[1.7]naphthyridine-3-carbonitrile under an inert atmosphere in 150 mL of methylene chloride was added 24 mL of oxalyl chloride followed by 0.4 mL of N,N-dimethyl formamide. After two hours at reflux, an additional 5 mL of oxalyl chloride and 0.3 mL of N,N-dimethyl formamide was added. After an additional hour at reflux, the reaction was poured into ice-water and solid potassium carbonate was added carefully to a pH of about 8. The chloroform layer was washed with brine, dried with sodium sulfate, and stripped to give a crude product. This material was further purified by passing it through a plug of silica gel with chloroform and recrystallizing from a mixture of chloroform and hexanes to give 10 g (92%) of 4-chloro-6-fluoro-[1.7]naphthyridine-3-carbonitrile as a yellowish solid: melting point 150-155° C.; mass spectrum (m/e): M+H2O-Cl 190.0.

後処理

  1. temperatureAfter two hours at reflux
  2. temperatureAfter an additional hour at reflux
  3. additionwas added carefully to a pH of about 8
  4. washThe chloroform layer was washed with brine
  5. dry with materialdried with sodium sulfate
  6. customto give a crude product
  7. customThis material was further purified
  8. customrecrystallizing from a mixture of chloroform and hexanes

出典と根拠

ORDレコード
ord-afc80517c3524f34a4b6c63d8ae6af10
出典データセット
uspto-grants-2002_03
特許番号
US06355636B1

反応ノート

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