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

Reaction equation

HRID 13017 reaction equation
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]

Participants

5

Reactant 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

Product 1

HCID 250136542,2,2-trifluoro-N-[(1R,2S)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-1-(4-methylsulfanylphenyl)propan-2-yl]acetamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(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%)

Workup

  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

Sources & evidence

ORD record
ord-c85fda72d8cd4530a5948340759c9843
Source dataset
uspto-grants-2010_06
Patent number
US07728030B2

Linked notes

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