{1-Azabicyclo[3.2.1]octan-5-yl}methanol → 1-Methyl-1H-indazole-3-carboxylic acid 1-azabicyclo[3.2.1]oct-5-ylmethyl ester

HRID 5387

반응식

HRID 5387 반응식
[N:1]12[CH2:8][C:5]([CH2:9][OH:10])([CH2:6][CH2:7]1)[CH2:4][CH2:3][CH2:2]2.C([Li])CCC.CCCCCC.N1([C:27]([C:29]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[N:31]([CH3:38])[N:30]=2)=[O:28])C=CNC1>O1CCCC1>[N:1]12[CH2:8][C:5]([CH2:9][O:10][C:27]([C:29]3[C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[N:31]([CH3:38])[N:30]=3)=[O:28])([CH2:6][CH2:7]1)[CH2:4][CH2:3][CH2:2]2

참가 물질

5

반응물 3

HCID 19795992{1-Azabicyclo[3.2.1]octan-5-yl}methanolHCID 197959943-(3H-imidazol-1-ylcarbonyl)-1-methyl-1H-indazoleHCID 178418244HCID 178418244, 화합물

생성물 1

HCID 537000391-Methyl-1H-indazole-3-carboxylic acid 1-azabicyclo[3.2.1]oct-5-ylmethyl ester수율 53.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A cooled (0° C.) solution of 1-azabicyclo[3.2.1]oct-5-ylmethanol (1.70 g, 12 mmol) in anhydrous tetrahydrofuran (15 mL) under nitrogen was treated (via syringe) with 2.45N n-butyllithium/hexane (12 mmol), then stirred at room temperature for thirty minutes and concentrated in vacuo to remove all hexane. Anhydrous tetrahydrofuran (15 mL) was added, followed by 3-(3H-imidazol-1-ylcarbonyl)-1-methyl-1H-indazole (2.49 g, 11 mmol), and the mixture was stirred under nitrogen at room temperature for 18 hours, then at 60° C. for three hours, and concentrated in vacuo. The residue was partitioned between 1.0N sodium carbonate (75 mL) and toluene (125 mL) containing some 2-propanol, and the organic layer was set aside. The aqueous solution was extracted with toluene (2×50 mL) containing some 2-propanol, and the combined organic solution was rinsed with water to remove imidazole, then dried azeotropically with toluene. The residue was filtered through alumina (eluted with 15% methanol/tetrahydrofuran), concentrated in vacuo, and triturated from ether/petroleum ethers (30°-60°), then recrystallized from ether/petroleum ethers (30°-60°) to afford 1.75 g (53%) of the product as a colorless solid; mp 93°-95° C.

후처리

  1. concentrationconcentrated in vacuo
  2. customto remove all hexane
  3. additionAnhydrous tetrahydrofuran (15 mL) was added
  4. stirringthe mixture was stirred under nitrogen at room temperature for 18 hours
  5. concentrationconcentrated in vacuo
  6. customThe residue was partitioned between 1.0N sodium carbonate (75 mL) and toluene (125 mL)
  7. additioncontaining some 2-propanol
  8. extractionThe aqueous solution was extracted with toluene (2×50 mL)
  9. additioncontaining some 2-propanol
  10. washthe combined organic solution was rinsed with water
  11. customto remove imidazole
  12. dry with materialdried azeotropically with toluene
  13. filtrationThe residue was filtered through alumina (eluted with 15% methanol/tetrahydrofuran)
  14. concentrationconcentrated in vacuo
  15. customtriturated from ether/petroleum ethers (30°-60°)
  16. customrecrystallized from ether/petroleum ethers (30°-60°)

출처 및 근거

ORD 기록
ord-4406e0402c004a7288caf0b804f30d30
출처 데이터셋
uspto-grants-1993_09
특허 번호
US05244907

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