Sodium Hydroxide → 6-(Piperidin-4-yloxy)-isoquinolin-5-ylamine

HRID 1022870노트

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HRID 1022870 반응식
[OH-].[Na+].[NH:3]1CCC[C@H]1C(O)=O.[N-]=[N+]=[N-].[Na+].C(OC([N:22]1[CH2:27][CH2:26][CH:25]([O:28][C:29]2[C:30](Br)=[C:31]3[C:36](=[CH:37][CH:38]=2)[CH:35]=[N:34][CH:33]=[CH:32]3)[CH2:24][CH2:23]1)=O)(C)(C)C>C(O)C.O.[Cu]I.C(OCC)(=O)C.O>[NH:22]1[CH2:27][CH2:26][CH:25]([O:28][C:29]2[C:30]([NH2:3])=[C:31]3[C:36](=[CH:37][CH:38]=2)[CH:35]=[N:34][CH:33]=[CH:32]3)[CH2:24][CH2:23]1

참가 물질

9

반응물 4

HCID 14798Sodium HydroxideHCID 33557Sodium AzideHCID 145742L-ProlineHCID 576469744-(5-Bromo-isoquinolin-6-yloxy)-piperidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 576469576-(Piperidin-4-yloxy)-isoquinolin-5-ylamine수율 123.4%

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 19096565Water ethanol용매

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온도
95 °C

실험 절차

60 μL of 1N NaOH-solution, 6.9 mg (0.3 eq) of L-proline, 3.8 mg (0.1 eq) of CuI and 26 mg (0.4 mmol) of NaN3 were added to a solution of 82 mg (0.2 mmol) of 4-(5-Bromo-isoquinolin-6-yloxy)-piperidine-1-carboxylic acid tert-butyl ester (11) in 2 mL of ethanol/water (7/3). The mixture was heated to 95° C. for 3 h in a microwave reactor (CEM Discover). After cooling water and ethyl acetate were added and the mixture was filtered through a celite cartridge. After removal of the solvents by distillation the remainder was subjected to preparative HPLC. The N-Boc-protected intermediate was deprotected by treatment with 2 mL 5-6 N HCl in isopropanol for 2 h at room temperature. Then water was added and all solvents were removed by freeze drying to yield 18 mg of compound 31 as hydrochloride.

후처리

  1. additionwere added
  2. filtrationthe mixture was filtered through a celite cartridge
  3. customAfter removal of the solvents
  4. distillationby distillation the remainder
  5. additionThen water was added
  6. customall solvents were removed by freeze
  7. customdrying

출처 및 근거

ORD 기록
ord-190a308d5817435b9cc730dd6f9102a1
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08722671B2

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