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

HRID 13017

反応式

HRID 13017 の反応式
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:17]3[C:12](=[CH:13][C:14]([O:18][C@H:19]([C:23]4[CH:28]=[CH:27][C:26]([S:29][CH3:30])=[CH:25][CH:24]=4)[C@@H:20]([NH2:22])[CH3:21])=[CH:15][CH:16]=3)[CH:11]=[N:10]2)=[CH:5][CH:4]=1.CN(C)C(N(C)C)=N.[F:39][C:40]([F:47])([F:46])[C:41](OCC)=[O:42]>CO>[F:39][C:40]([F:47])([F:46])[C:41]([NH:22][C@@H:20]([CH3:21])[C@H:19]([O:18][C:14]1[CH:13]=[C:12]2[C:17](=[CH:16][CH:15]=1)[N:9]([C:6]1[CH:7]=[CH:8][C:3]([F:2])=[CH:4][CH:5]=1)[N:10]=[CH:11]2)[C:23]1[CH:24]=[CH:25][C:26]([S:29][CH3:30])=[CH:27][CH:28]=1)=[O:42]

参加物

5

反応物 3

HCID 9794Ethyl trifluoroacetateHCID 664601,1,3,3-TetramethylguanidineHCID 66687724(1R,2S)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-[4-(methylthio)phenyl]propan-2-amine hydrochloride

生成物 1

HCID 250136542,2,2-trifluoro-N-[(1R,2S)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-1-(4-methylsulfanylphenyl)propan-2-yl]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-(methylthio)phenyl]propan-2-amine hydrochloride (9a) (150 mg, 0.34 mmol) was dissolved in MeOH (2 mL). 1,1,3,3-tetramethylguanidine (128 μL, 1.02 mmol) was added and the mixture was stirred for 5 min, ethyl trifluoroacetate (83 μL, 0.7 mmol) was added and the reaction mixture was stirred at r.t. for 2.5 h. The reaction mixture was evaporated and the residual material was purified by semi-preparative HPLC using a Kromasil® C18 250×20 mm, 5 μm column. Flow 10 mL/min, 20 min gradient of 20%-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. Yield 128 mg (74%)

後処理

  1. stirringthe reaction mixture was stirred at r.t. for 2.5 h
  2. customThe reaction mixture was evaporated
  3. customthe residual material was purified by semi-preparative HPLC
  4. customFlow 10 mL/min, 20 min gradient of 20%-90% MeCN in water
  5. concentrationconcentration until product
  6. washhad eluted

出典と根拠

ORDレコード
ord-c85fda72d8cd4530a5948340759c9843
出典データセット
uspto-grants-2010_06
特許番号
US07728030B2

関連ノート

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