Hydrochloric Acid → 2-((1-cyclopropyl-2-oxo-1H-imidazo[4,5-c]pyridin-3(2H)-yl)methyl)-3-isopentyl-3H-imidazo[4,5-b]pyridin-6-ylboronic acid

HRID 632861ノート

反応式

HRID 632861 の反応式
Br[C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([CH2:11][N:12]3[C:16]4[CH:17]=[N:18][CH:19]=[CH:20][C:15]=4[N:14]([CH:21]4[CH2:23][CH2:22]4)[C:13]3=[O:24])[N:8]([CH2:25][CH2:26][CH:27]([CH3:29])[CH3:28])[C:5]2=[N:6][CH:7]=1.[O:30]1CC[O:32][BH:31]1.C([O-])(=O)C.[K+].Cl>O1CCOCC1.CO.O>[CH:21]1([N:14]2[C:15]3[CH:20]=[CH:19][N:18]=[CH:17][C:16]=3[N:12]([CH2:11][C:9]3[N:8]([CH2:25][CH2:26][CH:27]([CH3:29])[CH3:28])[C:5]4=[N:6][CH:7]=[C:2]([B:31]([OH:32])[OH:30])[CH:3]=[C:4]4[N:10]=3)[C:13]2=[O:24])[CH2:23][CH2:22]1

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 517044Potassium AcetateHCID 5326306InChI=1/C2H5BO2/c1-2-5-3-4-1/h3H,1-2HHCID 679917843-((6-bromo-3-isopentyl-3H-imidazo[4,5-b]pyridin-2-yl)methyl)-1-cyclopropyl-1H-imidazo[4,5-c]pyridin-2(3H)-one

生成物 1

HCID 573788822-((1-cyclopropyl-2-oxo-1H-imidazo[4,5-c]pyridin-3(2H)-yl)methyl)-3-isopentyl-3H-imidazo[4,5-b]pyridin-6-ylboronic acid

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

The mixture of compound 16 (0.5 g, 1 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane (0.382 g, 1.5 mmol) and potassium acetate (0.16 g, 1.6 mmol) in dioxane (20 mL) under argon atmosphere was stirred at room temperature for 10 minutes. To the resulting mixture dichloro(diphenylphosphinoferrocene)palladium (39 mg, 0.05 mmol) was added. The resulting mixture was warmed to 115° C. for 3 hours. The mixture was allowed to cool down to room temperature then the solvent was removed. The residue (23-1) was dissolved in acetonitrile (40 mL) and an aqueous solution of hydrochloric acid 6 M (1.7 mL, 10 mmol) was added. The resulting mixture was stirred at 110° C. for 2 hours. The mixture was allowed to cool down to room temperature and water (30 mL) was added the pH was adjusted to pH=7 by addition of a solution 7N of ammoniac in methanol. The resulting mixture was concentrated and the residue was purified by preparative HPLC. The title compound 23 was isolated as a white solid (309 mg, 67%). m/z=421 (M+H)+.

後処理

  1. temperatureThe resulting mixture was warmed to 115° C. for 3 hours
  2. temperatureto cool down to room temperature
  3. customthe solvent was removed
  4. dissolutionThe residue (23-1) was dissolved in acetonitrile (40 mL)
  5. stirringThe resulting mixture was stirred at 110° C. for 2 hours
  6. temperatureto cool down to room temperature
  7. concentrationThe resulting mixture was concentrated
  8. customthe residue was purified by preparative HPLC

出典と根拠

ORDレコード
ord-21a5579e89744e86970d71b75b138248
出典データセット
uspto-grants-2016_04
特許番号
US09321767B2

反応ノート

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