Hydrochloric Acid → (E)-2-(4-((E)-1-(1H-Indazol-5-yl)-2-phenylbut-1-en-1-yl)phenyl)ethenesulfonamide

HRID 1057212ノート

反応式

HRID 1057212 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5](/[C:8](/[C:18]2[CH:19]=[C:20]3[C:24](=[CH:25][CH:26]=2)[N:23](C2CCCCO2)[N:22]=[CH:21]3)=[C:9](\[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)/[CH2:10][CH3:11])=[CH:4][CH:3]=1.[CH:33]([S:35]([NH2:38])(=[O:37])=[O:36])=[CH2:34].C(N(CC)CC)C.Cl>CN(C=O)C.CCO.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH:23]1[C:24]2[C:20](=[CH:19][C:18](/[C:8](/[C:5]3[CH:6]=[CH:7][C:2](/[CH:34]=[CH:33]/[S:35]([NH2:38])(=[O:37])=[O:36])=[CH:3][CH:4]=3)=[C:9](/[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)\[CH2:10][CH3:11])=[CH:26][CH:25]=2)[CH:21]=[N:22]1

参加物

9

反応物 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 520075Vinyl sulfonamideHCID 66802799(E)-5-(1-(4-Bromophenyl)-2-phenylbut-1-en-1-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

生成物 1

HCID 66802069(E)-2-(4-((E)-1-(1H-Indazol-5-yl)-2-phenylbut-1-en-1-yl)phenyl)ethenesulfonamide

試薬・触媒・溶媒 4

HCID 178418476HCID 178418476、化合物触媒HCID 702Ethanol溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
100 °C

実験手順

A mixture of (E)-5-(1-(4-bromophenyl)-2-phenylbut-1-en-1-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (0.1 g, 0.25 mmol), ethenesulfonamide (80 mg, 0.74 mmol), Pd(Ph3P)2Cl2 (18 mg, 0.025 mmol), triethylamine (0.25 g, 2.5 mmol) in DMF (1.25 mL) was degassed with 3 vacuum/nitrogen cycles, heated at 100° C. overnight, and then cooled to room temperature. The reaction mixture was diluted with water, extracted with EtOAc, washed with water, brine, dried over sodium sulfate, and filtered. The filtrate was concentrated down to give a residue that was redissolved in EtOH (2.5 ml). HCl (0.5 mL, 1.25 N HCl in ethanol) was added, and the mixture was heated at 80° C. for 1 h, diluted with water, and then extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with water, brine, dried over sodium sulfate, filtered, and concentrated to give the crude product. This crude material was purified on a RP-C18 column using 30-100% acetonitrile in water in the presence of 0.1% TFA to afford the title compound. LCMS: 430 (M+H)+.

後処理

  1. customwas degassed with 3 vacuum/nitrogen cycles
  2. temperaturecooled to room temperature
  3. additionThe reaction mixture was diluted with water
  4. extractionextracted with EtOAc
  5. washwashed with water, brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated down
  9. customto give a residue that
  10. temperaturethe mixture was heated at 80° C. for 1 h
  11. extractionextracted with ethyl acetate (2×50 mL)
  12. washThe combined organic layers were washed with water, brine
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customto give the crude product
  17. customThis crude material was purified on a RP-C18 column

出典と根拠

ORDレコード
ord-f1535e8e78424b5b8c384853afa896ac
出典データセット
uspto-grants-2016_07
特許番号
US09399646B2

反応ノート

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