Tetrahydrofuran → 8-(4-chlorophenyl)-7-p-tolyl-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

HRID 2101280ノート

反応式

HRID 2101280 の反応式
Cl[C:2]1[C:3]2[N:4]([C:15](=[O:29])[N:16]([CH2:18][C:19]3[CH:20]=[N:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=3)[N:17]=2)[CH:5]=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=1.C1COCC1.[Cl:35][C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1.C([O-])([O-])=O.[K+].[K+]>CO>[Cl:35][C:36]1[CH:41]=[CH:40][C:39]([C:2]2[C:3]3[N:4]([C:15](=[O:29])[N:16]([CH2:18][C:19]4[CH:20]=[N:21][C:22]([C:25]([F:27])([F:28])[F:26])=[CH:23][CH:24]=4)[N:17]=3)[CH:5]=[CH:6][C:7]=2[C:8]2[CH:9]=[CH:10][C:11]([CH3:14])=[CH:12][CH:13]=2)=[CH:38][CH:37]=1

参加物

6

反応物 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 742994-Chlorophenylboronic acidHCID 577993658-chloro-7-p-tolyl-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

生成物 1

HCID 160048708-(4-chlorophenyl)-7-p-tolyl-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one収率 27.1%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
70 °C

実験手順

To a stirring solution of 8-chloro-7-p-tolyl-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (28 mg, 0.067 mmol) in a 1:1 mixture of THF and methanol (4 mL) at room temperature under argon was added 4-chlorophenylboronic acid (12.5 g, 0.080 mmol), PXPd (11 g, 0.02 mmol), and K2CO3 (18.5 mg, 0.13 mmol). The resulting suspension was heated at 70° C. under argon for 10 min. Analysis by HPLC/MS indicated that starting material had been consumed. After cooling the reaction mixture to room temperature, water (25 mL) and EtOAc (25 mL) were added. The layers were separated. The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by preparative reverse phase HPLC (without TFA) to obtain 9 mg of the title compound as a white lyophilate. HPLC/MS: retention time=4.16 min, [M+H]+=495. 1H NMR (CDCl3): δ 8.79 (s, 1H), 7.95 (d, J=6.7 Hz, 1H), 7.83 (d, J=6.5 Hz, 1H) 7.69 (d, J=6.7 Hz, 1H), 7.29-7.18 (m, 4H), 7.12 (d, J=6.2 Hz, 2H), 7.00 (d, J=6.2 Hz, 2H), 6.70 (d, J=6.5 Hz, 1H), 5.27 (s, 2H), 2.32 (s, 3H).

後処理

  1. customhad been consumed
  2. temperatureAfter cooling the reaction mixture to room temperature
  3. additionwater (25 mL) and EtOAc (25 mL) were added
  4. customThe layers were separated
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by preparative reverse phase HPLC (without TFA)

出典と根拠

ORDレコード
ord-ed074032b5cc4665b67f83070f6e2ded
出典データセット
uspto-grants-2009_08
特許番号
US07572808B2

反応ノート

読み込み中…