Sodium hydride → 3-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid (6-methoxy-pyridazin-3-yl)-amide

HRID 1469385노트

반응식

HRID 1469385 반응식
[CH3:1][O:2][C:3]1[N:8]=[N:7][C:6]([NH2:9])=[CH:5][CH:4]=1.[H-].[Na+].[N+](C1C=CC([O:21][C:22]([N:24]2[CH2:27][CH:26]([O:28][C:29]3[CH:34]=[CH:33][C:32]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=4[F:41])=[CH:31][N:30]=3)[CH2:25]2)=O)=CC=1)([O-])=O>CN(C=O)C>[CH3:1][O:2][C:3]1[N:8]=[N:7][C:6]([NH:9][C:22]([N:24]2[CH2:25][CH:26]([O:28][C:29]3[CH:34]=[CH:33][C:32]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=4[F:41])=[CH:31][N:30]=3)[CH2:27]2)=[O:21])=[CH:5][CH:4]=1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 816736-Methoxypyridazin-3-amineHCID 580731093-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid 4-nitro-phenyl ester

생성물 1

HCID 442192123-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid (6-methoxy-pyridazin-3-yl)-amide수율 37%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

To a solution of 6-Methoxy-pyridazin-3-ylamine (39 mg, 0.31 mmol, [Cas. No. 7252-84-8]) in DMF (3 mL) at 0° C. was added sodium hydride (20 mg, 0.5 mmol, 60% disp. in mineral oil). After stirring at 0° C. for 15 min. a solution of 3-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid 4-nitro-phenyl ester (102 mg, 0.25 mmol) in DMF (4 mL) was added dropwise. After stirring for 16 hrs at ambient temperature the reaction mixture was concentrated in vacuo, diluted with ethyl acetate (50 mL) and washed sequentially with sat. aqueous sodium hydrogen carbonate solution (2×50 mL) then sat. sodium chloride solution (50 mL). Mixture dried over magnesium sulphate and filtered. Filtrate solvents were removed in vacuo and the residue was purified by flash chromatography (ethyl acetate) to give the title compound (35 mg, 37%)

후처리

  1. additionwas added dropwise
  2. concentrationwas concentrated in vacuo
  3. additiondiluted with ethyl acetate (50 mL)
  4. washwashed sequentially with sat. aqueous sodium hydrogen carbonate solution (2×50 mL)
  5. dry with materialMixture dried over magnesium sulphate
  6. filtrationfiltered
  7. customFiltrate solvents were removed in vacuo
  8. customthe residue was purified by flash chromatography (ethyl acetate)

출처 및 근거

ORD 기록
ord-ac0396eadfae46ef98b1c079f8a9da17
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09006269B2

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