Potassium Carbonate → 1-((5-(benzyloxy)-6-methylpyridin-2-yl)methyl)-3-cyclopropyl-4-nitro-1H-indazole

HRID 79483ノート

反応式

HRID 79483 の反応式
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:16][N:17]2[C:25]3[C:20](=[C:21]([N+:26]([O-:28])=[O:27])[CH:22]=[CH:23][CH:24]=3)[C:19](Br)=[N:18]2)=[N:13][C:14]=1[CH3:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:30]1(B(O)O)[CH2:32][CH2:31]1.C([O-])([O-])=O.[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=C(S([O-])(=O)=O)C=2OC)CCCCC1.[Na+]>C(O[Pd]OC(=O)C)(=O)C.O1CCOCC1.O>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:16][N:17]2[C:25]3[C:20](=[C:21]([N+:26]([O-:28])=[O:27])[CH:22]=[CH:23][CH:24]=3)[C:19]([CH:30]3[CH2:32][CH2:31]3)=[N:18]2)=[N:13][C:14]=1[CH3:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 23677046Sodium 2'-(dicyclohexylphosphino)-2,6-dimethoxybiphenyl-3-sulfonateHCID 672601791-((5-(benzyloxy)-6-methylpyridin-2-yl)methyl)-3-bromo-4-nitro-1H-indazole

生成物 1

HCID 672611071-((5-(benzyloxy)-6-methylpyridin-2-yl)methyl)-3-cyclopropyl-4-nitro-1H-indazole

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 218864351,4-Dioxane--water (1/1)溶媒

反応条件

温度
0 °C

実験手順

A first flask was charged with 1,4-dioxane/H2O (50 mL/10 mL). The flask was cooled to 0° C. and vacuum was applied for 20 minutes. A second flask was charged with 1-((5-(benzyloxy)-6-methylpyridin-2-yl)methyl)-3-bromo-4-nitro-1H-indazole (6.07 g, 13.4 mmol), cyclopropylboronic acid (4.60 g, 53.6 mmol), diacetoxypalladium (0.150 g, 0.670 mmol), K2CO3 (5.55 g, 40.2 mmol) and sodium 2′-(dicyclohexylphosphino)-2,6-dimethoxybiphenyl-3-sulfonate (0.686 g, 1.34 mmol). The second flask was also evacuated with vacuum and back filled with N2 for 3 times. The cold degassed dioxane/H2O was added to the second flask, which was evacuated with vacuum and back filled with argon for 5 times. The reaction mix was then heated to 80° C. for 3 hours. A sample (1H NMR) taken from the flask showed complete reaction at this point. The reaction was cooled to ambient temperature, filtered and concentrated under reduced pressure. The residue was diluted with EtOAc (200 mL). The organic layer was washed with saturated NaHCO3, dried (Na2SO4) and concentrated to give desired product, which was used in the next step without further purification.

後処理

  1. customThe second flask was also evacuated with vacuum
  2. additionback filled with N2 for 3 times
  3. customThe cold degassed dioxane/H2O
  4. additionwas added to the second flask, which
  5. customwas evacuated with vacuum
  6. additionback filled with argon for 5 times
  7. additionThe reaction mix
  8. temperaturewas then heated to 80° C. for 3 hours
  9. customreaction at this point
  10. temperatureThe reaction was cooled to ambient temperature
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. additionThe residue was diluted with EtOAc (200 mL)
  14. washThe organic layer was washed with saturated NaHCO3
  15. dry with materialdried (Na2SO4)
  16. concentrationconcentrated

出典と根拠

ORDレコード
ord-cdadfd5a8d8b40fcb37fc3ab20359451
出典データセット
uspto-grants-2014_09
特許番号
US08841455B2

反応ノート

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