Phosphorus oxychloride → [4-Chloro-3-methyl-1-(2-pyridinyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]phenylmethanone

HRID 497937ノート

反応式

HRID 497937 の反応式
O[C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][N:5]=[C:4]2[N:11]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)[N:12]=[C:13]([CH3:14])[C:3]=12.P(Cl)(Cl)(Cl)=O.[C:26]1([Mg]Br)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[Cl-:34].[NH4+]>>[Cl:34][C:2]1[C:7]([C:8]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:10])=[CH:6][N:5]=[C:4]2[N:11]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)[N:12]=[C:13]([CH3:14])[C:3]=12

参加物

5

反応物 4

HCID 24813Phosphorus oxychlorideHCID 25517Ammonium ChlorideHCID 178418255HCID 178418255、化合物HCID 178433901HCID 178433901、化合物

生成物 1

HCID 22320099[4-Chloro-3-methyl-1-(2-pyridinyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]phenylmethanone収率 38%

反応条件

温度
100 °C

実験手順

A solution of 4-hydroxy-3-methyl-1-(2-pyridinyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (2.0 g, 7.4 mmol) in phosphorous oxychloride (19 mL, 200 mmol) was heated and stirred at 100° C. for 1.5 hours. After the solution was cooled to room temperature, the solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (50 mL) and cooled to −78° C. To the solution, a solution of phenylmagnesium bromide (1M tetrahydrofuran solution, 30 mL, 30 mmol) was added dropwise at the same temperature, and the mixture was stirred for 1 hour, and at room temperature further for 0.5 hour. The mixture was poured into an aqueous saturated ammonium chloride solution and organic matter was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. Purification of the residue by silica gel chromatography (hexane:chloroform:ethyl acetate=2:1:1 to 1:1:1) gave the title compound (0.83 g, 38% yield).

後処理

  1. temperatureAfter the solution was cooled to room temperature
  2. customthe solvent was evaporated under reduced pressure
  3. dissolutionThe residue was dissolved in tetrahydrofuran (50 mL)
  4. temperaturecooled to −78° C
  5. stirringthe mixture was stirred for 1 hour
  6. waitat room temperature further for 0.5 hour
  7. extractionwas extracted with ethyl acetate
  8. washThe extract was washed with saturated brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. customthe solvent was evaporated under reduced pressure
  11. customPurification of the residue by silica gel chromatography (hexane:chloroform:ethyl acetate=2:1:1 to 1:1:1)

出典と根拠

ORDレコード
ord-8c65a0d6655b4138972321d5491f356a
出典データセット
uspto-grants-2005_09
特許番号
US06949648B2

反応ノート

読み込み中…