Nitrogen → (S)-tert-Butyl 4-(4,5-dimethyl-6-phenylpyridazin-3-yl)-2-methylpiperazine-1-carboxylate

HRID 2093359ノート

反応式

HRID 2093359 の反応式
N#N.Cl[C:4]1[N:9]=[N:8][C:7]([N:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C@@H:12]([CH3:23])[CH2:11]2)=[C:6]([CH3:24])[C:5]=1[CH3:25].[C:26]1(B(O)O)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[F-].[Cs+]>O1CCOCC1>[CH3:24][C:6]1[C:5]([CH3:25])=[C:4]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[N:9]=[N:8][C:7]=1[N:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C@@H:12]([CH3:23])[CH2:11]1

参加物

6

反応物 4

HCID 947NitrogenHCID 25953Cesium fluorideHCID 66827Phenylboronic AcidHCID 58359254(S)-tert-butyl 4-(6-chloro-4,5-dimethylpyridazin-3-yl)-2-methylpiperazine-1-carboxylate

生成物 1

HCID 58359248(S)-tert-Butyl 4-(4,5-dimethyl-6-phenylpyridazin-3-yl)-2-methylpiperazine-1-carboxylate収率 86.4%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
95 °C

実験手順

Treat a N2 degassed mixture of (S)-tert-butyl 4-(6-chloro-4,5-dimethylpyridazin-3-yl)-2-methylpiperazine-1-carboxylate (3.03 g, 8.87 mmol), phenylboronic acid (1.62 g, 13.3 mmol), and CsF (4.09 g, 26.9 mmol) in 1,4-dioxane (120 mL) with (1,1′-bis(diphenylphosphino)ferrocene)palladium(II) chloride (1.08 g, 1.32 mmol). Heat the reaction mixture at 95° C. overnight. Cool the reaction, and partition between EtOAc and H2O. Wash the organic layer with brine, dry over Na2SO4, filter, and concentrate under reduced pressure. Purify the residue by flash silica gel chromatography (gradient of 15 to 85% EtOAc in hexanes) to afford the title compound as a white solid (2.93 g, 86%). ES/MS m/z 383.0 (M+1).

後処理

  1. customdegassed
  2. temperatureCool
  3. customthe reaction
  4. custompartition between EtOAc and H2O
  5. washWash the organic layer with brine
  6. dry with materialdry over Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate under reduced pressure
  9. customPurify the residue by flash silica gel chromatography (gradient of 15 to 85% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-02ab26925b524505a6e29cd6bc0292a9
出典データセット
uspto-grants-2013_05
特許番号
US08445493B2

反応ノート

読み込み中…