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

HRID 1897473

반응식

HRID 1897473 반응식
[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

참가 물질

8

반응물 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 106428511-(tert-Butoxycarbonyl)-4-((p-toluenesulfonyloxy)methyl)piperidineHCID 1361636625-(2,4-difluorophenoxy)-1-isobutyl-1H-indazol-6-ol

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매

반응 조건

온도
70 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-fad0e35ec10e4fc48b85ad9a4d80eb5a
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08518983B2

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