碘化钠 → 5-(2,4-difluorophenoxy)-1-isobutyl-6-(piperidin-4-ylmethoxy)-1H-indazole

HRID 1715613

反应方程式

HRID 1715613 反应方程式
[F:1][C:2]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[OH:14])[N:10]([CH2:15][CH:16]([CH3:18])[CH3:17])[N:9]=[CH:8]2.C(OC([N:31]1[CH2:36][CH2:35][CH:34]([CH2:37]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:33][CH2:32]1)=O)(C)(C)C.[Na+].[I-].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOCC.O>[F:1][C:2]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[O:14][CH2:37][CH:34]1[CH2:35][CH2:36][NH:31][CH2:32][CH2:33]1)[N:10]([CH2:15][CH:16]([CH3:18])[CH3:17])[N:9]=[CH:8]2

参与物

8

反应物 4

HCID 5238碘化钠HCID 11430碳酸钾HCID 106428511-N-BOC-4-(4-甲基苯磺酰氧甲基)哌啶HCID 1361636625-(2,4-difluorophenoxy)-1-isobutyl-1H-indazol-6-ol

产物 1

HCID 426111405-(2,4-difluorophenoxy)-1-isobutyl-6-(piperidin-4-ylmethoxy)-1H-indazole收率 39.3%

试剂、催化剂与溶剂 3

HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂HCID 3283乙醚溶剂HCID 6228N,N-二甲基甲酰胺溶剂

反应条件

温度
70 °C

实验过程

To a solution of 5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazol-6-ol (0.06 g, 0.19 mmol) and 4-(toluene-4-sulfonyloxymethyl)-piperidine-1-carboxylic acid tert-butyl ester (0.08 g, 0.20 mmol) in DMF (3 mL) was added NaI (0.014 g, 0.009 mmol) and K2CO3 (0.08 g, 0.56 mmol). The reaction mixture was heated to 70° C. for 20 hours. The mixture was diluted with ether and water and the layers were separated. The aqueous layer was extracted with ether (2×) and the combined organic layers were washed with water and brine, and dried over Na2SO4. The crude mixture was concentrated under reduced pressure and purified by reverse phase HPLC. The desired fraction was concentrated to 0.037 g that was then treated with HCl (4N in dioxane) for 7 hours. The solvent was removed under reduced pressure and the final product was dried under high vacuum to obtain 0.031 g solid (37% yield). MS (APCI+) m/z 416 (M+1) detected.

后处理

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted with ether (2×)
  3. washthe combined organic layers were washed with water and brine
  4. dry with materialdried over Na2SO4
  5. concentrationThe crude mixture was concentrated under reduced pressure
  6. custompurified by reverse phase HPLC
  7. concentrationThe desired fraction was concentrated to 0.037 g that
  8. additionwas then treated with HCl (4N in dioxane) for 7 hours
  9. customThe solvent was removed under reduced pressure
  10. dry with materialthe final product was dried under high vacuum

来源与证据

ORD记录
ord-227dd0eef5ea49f4bb697e42853ff06a
来源数据集
uspto-grants-2010_09
专利号
US07799782B2

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