Ethyl trifluoroacetate → N-[(1R,2S)-1-(4-cyclopropylsulfanylphenyl)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-propan-2-yl]-2,2,2-trifluoro-acetamide

HRID 13018

反応式

HRID 13018 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][C@H:18]([C:22]4[CH:27]=[CH:26][C:25]([S:28][CH:29]5[CH2:31][CH2:30]5)=[CH:24][CH:23]=4)[C@@H:19]([NH2:21])[CH3:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.CN(C)C(N(C)C)=N.[F:40][C:41]([F:48])([F:47])[C:42](OCC)=[O:43]>CO>[CH:29]1([S:28][C:25]2[CH:24]=[CH:23][C:22]([C@@H:18]([O:17][C:13]3[CH:12]=[C:11]4[C:16](=[CH:15][CH:14]=3)[N:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[N:9]=[CH:10]4)[C@@H:19]([NH:21][C:42](=[O:43])[C:41]([F:48])([F:47])[F:40])[CH3:20])=[CH:27][CH:26]=2)[CH2:31][CH2:30]1

参加物

5

反応物 3

HCID 9794Ethyl trifluoroacetateHCID 664601,1,3,3-TetramethylguanidineHCID 59339850(1R,2S)-1-{[1-(4-Fluorophenyl)-1H-indazol-5-yl]oxy}-1-[4-(cyclopropylthio)phenyl]propan-2-amine

生成物 1

HCID 25013809N-[(1R,2S)-1-(4-cyclopropylsulfanylphenyl)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-propan-2-yl]-2,2,2-trifluoro-acetamide

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

(1R,2S)-1-{[1-(4-Fluorophenyl)-1H-indazol-5-yl]oxy}-1-[4-(cyclopropylthio)phenyl]propan-2-amine (62 mg, 0.14 mmol) was dissolved in MeOH (2 mL), 1,1,3,3-tetramethylguanidine (100 μL, 0.8 mmol) and ethyl trifluoroacetate (83 μL, 0.7 mmol) was added. The mixture was stirred at r.t. for 2 h, the solvents was removed by evaporation and the residual material was treated with water and a few drops of dilute HCl(aq) until slightly acidic. The formed slurry was extracted with DCM and EtOAc, the combined organic phases was concentrated and purified by semi-preparative HPLC using a Kromasil® C18 250×20 mm, 5 μm column. Flow 10 mL/min, 15 min gradient of 50%-90% MeCN in water followed by isocratic final concentration until product had eluted. UV=254 nm was used for detection. Fractions with product was combined and lyophilized to afford the title compound as a colourless solid.

後処理

  1. customthe solvents was removed by evaporation
  2. additionthe residual material was treated with water and a few drops of dilute HCl(aq) until slightly acidic
  3. extractionThe formed slurry was extracted with DCM and EtOAc
  4. concentrationthe combined organic phases was concentrated
  5. custompurified by semi-preparative HPLC
  6. customFlow 10 mL/min, 15 min gradient of 50%-90% MeCN in water
  7. concentrationconcentration until product
  8. washhad eluted

出典と根拠

ORDレコード
ord-ef94b86e7a164d3980da150c13c2d8ec
出典データセット
uspto-grants-2010_06
特許番号
US07728030B2

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