2-Pyrazinecarboxylic acid → 4-(4-Fluoro-phenoxy)-2-pyridin-2-yl-6-(pyridin-3-yloxy)-1H-benzimidazole

HRID 13248

반응식

HRID 13248 반응식
N1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:7](O)=O.Cl.[CH2:11](N=C=NCCCN(C)C)C.[F:22][C:23]1[CH:44]=[CH:43][C:26]([O:27][C:28]2[CH:33]=[C:32]([O:34][C:35]3[CH:36]=[N:37][CH:38]=[CH:39][CH:40]=3)[CH:31]=[C:30]([NH2:41])[C:29]=2[NH2:42])=[CH:25][CH:24]=1.FC1C=CC(O)=CC=1.OC1C=NC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.C(OCC)(=O)C.N1C=CC=CC=1>[F:22][C:23]1[CH:44]=[CH:43][C:26]([O:27][C:28]2[C:29]3[N:42]=[C:7]([C:2]4[CH:11]=[CH:6][CH:5]=[CH:4][N:3]=4)[NH:41][C:30]=3[CH:31]=[C:32]([O:34][C:35]3[CH:36]=[N:37][CH:38]=[CH:39][CH:40]=3)[CH:33]=2)=[CH:25][CH:24]=1

참가 물질

10

반응물 6

HCID 10472-Pyrazinecarboxylic acidHCID 79713-HydroxypyridineHCID 97324-FluorophenolHCID 521998p-Toluenesulfonic acid monohydrateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 231454153-(4-Fluorophenoxy)-5-(pyridin-3-yloxy)-benzene-1,2-diamine

생성물 1

HCID 231452784-(4-Fluoro-phenoxy)-2-pyridin-2-yl-6-(pyridin-3-yloxy)-1H-benzimidazole

시약·촉매·용매 3

HCID 1049Pyridine용매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

실험 절차

18.6 mg of pyrazine-2-carboxylic acid and 57.5 mg of 1-ethyl-3-(3′-dimethylaminopropyl)-carbodiimide hydrochloride were added to a pyridine (2 ml) solution of 46.7 mg of 3-(4-fluorophenoxy)-5-(pyridin-3-yloxy)-benzene-1,2-diamine produced in the same manner as in Example 67 but using 4-fluorophenol and 3-hydroxypyridine, and the reaction liquid was stirred overnight, and then pyridine was evaporated away under reduced pressure. The residue was diluted with ethyl acetate, washed with water, and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure to obtain a mixture of amides as a yellow oily substance. The resulting mixture of amides was dissolved in 3 ml of toluene, and 28 mg of p-toluenesulfonic acid monohydrate was added to it, and the reaction liquid was stirred overnight at 120° C. The reaction liquid was diluted with ethyl acetate, washed with aqueous saturated sodium bicarbonate, and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=20/1) to obtain the entitled compound as a yellow solid.

후처리

  1. customproduced in the same manner as in Example 67
  2. customthe reaction liquid
  3. custompyridine was evaporated away under reduced pressure
  4. additionThe residue was diluted with ethyl acetate
  5. washwashed with water
  6. dry with materialdried with anhydrous magnesium sulfate
  7. customThe solvent was evaporated away under reduced pressure
  8. customto obtain
  9. customthe reaction liquid
  10. stirringwas stirred overnight at 120° C
  11. customThe reaction liquid
  12. washwashed with aqueous saturated sodium bicarbonate
  13. dry with materialdried with anhydrous magnesium sulfate
  14. customThe solvent was evaporated away under reduced pressure
  15. customthe resulting residue was purified
  16. customthrough partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=20/1)

출처 및 근거

ORD 기록
ord-a85a286adeb14b4994ff41835eaf05ce
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07728025B2

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