N-(3-Aminopropyl)morpholine → {3-(4-Fluorophenyl)(1h-indazol-5-yl)}-n-(3-morpholin-4-ylpropyl)carboxamide

HRID 1272760노트

반응식

HRID 1272760 반응식
[NH2:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.C([N:14]1[C:22]2[C:17](=[CH:18][C:19]([C:23](Cl)=[O:24])=[CH:20][CH:21]=2)[C:16]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)=[N:15]1)(=O)C>N1C=CC=CC=1>[F:32][C:29]1[CH:28]=[CH:27][C:26]([C:16]2[C:17]3[C:22](=[CH:21][CH:20]=[C:19]([C:23]([NH:1][CH2:2][CH2:3][CH2:4][N:5]4[CH2:10][CH2:9][O:8][CH2:7][CH2:6]4)=[O:24])[CH:18]=3)[NH:14][N:15]=2)=[CH:31][CH:30]=1

참가 물질

4

반응물 2

HCID 61055N-(3-Aminopropyl)morpholine2회HCID 224802271-acetyl-3-(4-fluorophenyl)-1H-indazole-5-carbonyl chloride

생성물 1

HCID 9999949{3-(4-Fluorophenyl)(1h-indazol-5-yl)}-n-(3-morpholin-4-ylpropyl)carboxamide수율 13.5%

시약·촉매·용매 1

HCID 1049Pyridine용매2회

실험 절차

To a flask containing a solution of 4-(3-Aminopropyl)-morpholine (117 μl, 0.79 mmol) in pyridine (1 mL) was added 1-acetyl-3-(4-fluorophenyl)-1H-indazole-5-carbonyl chloride (230 mg, 0.72 mmol) dissolved in pyridine (5 mL). The reaction was allowed to stir under a nitrogen atmosphere overnight. The reaction was not complete so an additional equivalent of 4-(3-Aminopropyl)-morpholine (100 μl, 0.72 mmol) was added. The reaction was allowed to stir at room temperature overnight. LCMS showed the product formation. Solvent was removed by rotary evaporation. The reaction was treated with water and the product was extracted with ethyl acetate and dichloromethane. The organic layers were combined and washed with saturated aqueous sodium carbonate solution and brine. The organic layer was dried with magnesium sulfate, filtered and concentrated to yield the product. This was purified by semi-preparative HPLC. The product was washed with a sodium bicarbonate solution to remove the TFA salt to yield the title compound (37.3 mg, 13.5% yield). 1H NMR (DMSO-d6) δ 8.6 (m, 1H), 8.5 (m, 1H), 8.0 (m, 2H), 7.9 (m, 1H), 7.7 (m, 1H), 7.4 (m, 2H), 3.3 (m, 4H), 3.1 (m, 2H), 2.3 (m, 6H), 1.6 (m, 2H) ES-MS m/z 383 [M+1]+.

후처리

  1. additionwas added
  2. stirringto stir at room temperature overnight
  3. customSolvent was removed by rotary evaporation
  4. additionThe reaction was treated with water
  5. extractionthe product was extracted with ethyl acetate and dichloromethane
  6. washwashed with saturated aqueous sodium carbonate solution and brine
  7. dry with materialThe organic layer was dried with magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto yield the product
  11. customThis was purified by semi-preparative HPLC
  12. washThe product was washed with a sodium bicarbonate solution
  13. customto remove the TFA salt

출처 및 근거

ORD 기록
ord-5784733cab3f4caabf97b68f973992cb
출처 데이터셋
uspto-grants-2007_04
특허 번호
US07208513B2

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