Diethyl Ether → N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-acetyl-6-methylpyrimidinamine

HRID 1251503ノート

反応式

HRID 1251503 の反応式
[Br:1][C:2]1[CH:7]=[C:6]([CH:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[N:11]([CH2:22][CH3:23])[C:12]1[N:17]=[C:16]([C:18]([OH:20])=O)[CH:15]=[C:14]([CH3:21])[N:13]=1.C[Li].[CH3:26]COCC.C(OCC)(=O)C>C1COCC1>[Br:1][C:2]1[CH:7]=[C:6]([CH:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[N:11]([CH2:22][CH3:23])[C:12]1[N:17]=[C:16]([C:18](=[O:20])[CH3:26])[CH:15]=[C:14]([CH3:21])[N:13]=1

参加物

6

反応物 4

HCID 3283Diethyl Ether2 回HCID 8857Ethyl AcetateHCID 18323680N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-carboxy-6-methylpyrimidinamineHCID 178418348HCID 178418348、化合物2 回

生成物 1

HCID 18323676N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-acetyl-6-methylpyrimidinamine収率 68%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

A solution of N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-carboxy-6-methylpyrimidinamine (3.7 g, 9.8 mmol) in anhydrous THF (25 mL) was cooled with stirring to −78° C. under a nitrogen atmosphere. A solution of methyl lithium in ether (1.4 M, 7 mL, 9.8 mmol) was added dropwise and the reaction mixture was stirred at −78° C. for 1 h. The CeCl3 suspension was transferred via cannula into the reaction mixture and stirring at −78° C. was continued for 5 h. A solution of methyl lithium in ether (1.4 M, 7 mL, 9.8 mmol) was added dropwise and the reaction mixture was then warmed gradually to room temperature over 16 h. After cooling the reaction mixture to −78° C., the reaction was quenched with a 1 N HCl solution and warmed to room temperature. The resulting mixture was extracted three times with ethyl acetate. The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to give an orange yellow oil. Column chromatography (ethyl acetate:hexanes::1:4) afforded the title product as an oil (2.5 g, 68% yield, Rf 0.5): NMR (CDCl3, 300 MHz): 7.55 (d, 1H, J=1), 7.25-7.15 (m, 2H), 6.95 (s, 1H), 4.30-4.10 (m, 1H), 3.90-3.70 (m, 1H), 3.00-2.85 (m, 1H), 2.80-2.05 (m, 6H), 1.35-1.20 (m, 9H); CI-HRMS: Calcd (C18H22BrN3O): 376.1024 (M+H), Found: 376.1042.

後処理

  1. stirringthe reaction mixture was stirred at −78° C. for 1 h
  2. stirringstirring at −78° C.
  3. temperaturethe reaction mixture was then warmed gradually to room temperature over 16 h
  4. temperatureAfter cooling the reaction mixture to −78° C.
  5. customthe reaction was quenched with a 1 N HCl solution
  6. temperaturewarmed to room temperature
  7. extractionThe resulting mixture was extracted three times with ethyl acetate
  8. dry with materialThe combined organic layers were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give an orange yellow oil

出典と根拠

ORDレコード
ord-6b535c4ec17b496985480bdf766bf88f
出典データセット
uspto-grants-2002_01
特許番号
US06342503B1

反応ノート

読み込み中…