Sodium Carbonate → 7-(4-chlorophenyl)-5-methyl-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

HRID 2101380ノート

反応式

HRID 2101380 の反応式
Br[C:2]1[C:3]2[N:4]([C:16](=[O:31])[N:17]([CH2:19][C:20]3[C:21]([CH3:30])=[N:22][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:24][CH:25]=3)[N:18]=2)[C:5]([CH3:15])=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=1.CC1(C)C(C)(C)OB([C:40]2[CH:45]=[CH:44][N:43]=[CH:42][CH:41]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:14][C:11]1[CH:10]=[CH:9][C:8]([C:7]2[CH:6]=[C:5]([CH3:15])[N:4]3[C:16](=[O:31])[N:17]([CH2:19][C:20]4[C:21]([CH3:30])=[N:22][C:23]([C:26]([F:29])([F:27])[F:28])=[CH:24][CH:25]=4)[N:18]=[C:3]3[C:2]=2[C:40]2[CH:45]=[CH:44][N:43]=[CH:42][CH:41]=2)=[CH:13][CH:12]=1

参加物

7

反応物 3

HCID 10340Sodium CarbonateHCID 27346484-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 577994468-bromo-7-(4-chlorophenyl)-5-methyl-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

生成物 1

HCID 577994397-(4-chlorophenyl)-5-methyl-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one収率 161.8%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

To a suspension of 8-bromo-7-(4-chlorophenyl)-5-methyl-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (53 mg, 0.103 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (84 mg, 0.414 mmol), and 2.0 M aqueous sodium carbonate (1 mL, 2 mmol) in toluene (2 mL) was added (Ph3P)4Pd (36 mg, 0.03 mmol), and the resulting yellow mixture was vigorously stirred under argon at 100° C. for 16 h. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EtOAc (20 mL×3). The combined EtOAc extracts were washed with water, then saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified using a silica gel cartridge (12 g) eluted with a gradient of EtOAc (30-70%) in hexanes to obtain 85 mg of the desired product, which was contaminated with triphenylphosphine oxide. The product was further purified using preparative reverse phase HPLC (Phenomenex Luna 5 μm C-18 21.2×100 mm column eluted with a linear gradient of 50% to 90% B over 10 min (A=90% water, 10% methanol and B=90% methanol, 10% water) with flow rate at 20 mL/min and UV detection at 220 nm). The desired fractions were concentrated under reduced pressure. The residue was dissolved in acetonitrile, frozen and lyophilized to afford 32 mg (62%) of the title compound as a light yellow powder. HPLC/MS: retention time=3.00 min, [M+H]+=510.4.

後処理

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with EtOAc (20 mL×3)
  3. washThe combined EtOAc extracts were washed with water
  4. dry with materialsaturated aqueous NaCl, dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified
  8. washeluted with a gradient of EtOAc (30-70%) in hexanes

出典と根拠

ORDレコード
ord-47bfbc21ae4541a0a42942fd06bcf2cd
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…