Sodium Cyanide → 7-Tert-butyl-3-[3-chloro-2-(hydroxymethyl)phenyl]-4-oxo-3,4-dihydrophthalazine-5-carbonitrile

HRID 1025558ノート

反応式

HRID 1025558 の反応式
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13](F)[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=1[CH2:24][OH:25])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[C-:26]#[N:27].[Na+]>CS(C)=O>[C:1]([C:5]1[CH:14]=[C:13]([C:26]#[N:27])[C:12]2[C:11](=[O:16])[N:10]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=3[CH2:24][OH:25])[N:9]=[CH:8][C:7]=2[CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

参加物

4

反応物 2

HCID 8929Sodium Cyanide2 回HCID 594737806-(tert-butyl)-2-(3-chloro-2-(hydroxymethyl)phenyl)-8-fluorophthalazin-1(2H)-one

生成物 1

HCID 710082447-Tert-butyl-3-[3-chloro-2-(hydroxymethyl)phenyl]-4-oxo-3,4-dihydrophthalazine-5-carbonitrile収率 57%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
80 °C

実験手順

To a 100 mL round-bottomed flask were added 6-tert-butyl-2-[3-chloro-2-(hydroxymethyl)phenyl]-8-fluorophthalazin-1(2H)-one (671 mg, 1.86 mmol, prepared according to US2010/0222325), sodium cyanide (365 mg, 7.44 mmol) and DMSO (10 mL) to give a light yellow suspension. The mixture was stirred at 80° C. for 16 hrs. Additional sodium cyanide (182 mg, 3.72 mmol) was added and the mixture was further stirred at 80° C. for 60 hrs. The mixture was cooled to room temperature and extracted with ethyl acetate and water. The organic layer was washed with water and brine, dried over sodium sulfate and filtered. Solvents were evaporated and the residue was purified through flash column chromatography (220 g silica gel, 0% to 40% acetone in heptane) to give 7-tert-butyl-3-[3-chloro-2-(hydroxymethyl)phenyl]-4-oxo-3,4-dihydrophthalazine-5-carbonitrile as a yellow solid (390 mg, 57% yield).

後処理

  1. customprepared
  2. customto give a light yellow suspension
  3. stirringthe mixture was further stirred at 80° C. for 60 hrs
  4. temperatureThe mixture was cooled to room temperature
  5. extractionextracted with ethyl acetate and water
  6. washThe organic layer was washed with water and brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customSolvents were evaporated
  10. customthe residue was purified through flash column chromatography (220 g silica gel, 0% to 40% acetone in heptane)

出典と根拠

ORDレコード
ord-641c294d5850415c8ac1460c533b79c6
出典データセット
uspto-grants-2014_05
特許番号
US08729078B2

反応ノート

読み込み中…