Ethyl Acetate → Methyl 3-(4-{[4-[5-fluoro-2-(methyloxy)phenyl]-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino}-6-methyl-1H-indazol-1-yl)benzoate

HRID 1925595Notes

Reaction equation

HRID 1925595 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][CH3:20])=[C:6]([C:8]([CH3:18])([CH3:17])[CH2:9][C:10]2([C:13]([F:16])([F:15])[F:14])[CH2:12][O:11]2)[CH:7]=1.[NH2:21][C:22]1[CH:30]=[C:29]([CH3:31])[CH:28]=[C:27]2[C:23]=1[CH:24]=[N:25][N:26]2[C:32]1[CH:33]=[C:34]([CH:39]=[CH:40][CH:41]=1)[C:35]([O:37][CH3:38])=[O:36].FC(F)(F)S([O-])(=O)=O.[Yb+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O.C(OCC)(=O)C>C(#N)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][CH3:20])=[C:6]([C:8]([CH3:18])([CH3:17])[CH2:9][C:10]([OH:11])([C:13]([F:16])([F:15])[F:14])[CH2:12][NH:21][C:22]2[CH:30]=[C:29]([CH3:31])[CH:28]=[C:27]3[C:23]=2[CH:24]=[N:25][N:26]3[C:32]2[CH:33]=[C:34]([CH:39]=[CH:40][CH:41]=2)[C:35]([O:37][CH3:38])=[O:36])[CH:7]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 2733225Ytterbium triflateHCID 160992392-[2-(5-Fluoro-2-methoxyphenyl)-2-methylpropyl]-2-trifluoromethyloxiraneHCID 57672644Methyl 3-(4-amino-6-methyl-1H-indazol-1-yl)benzoate

Product 1

HCID 57672643Methyl 3-(4-{[4-[5-fluoro-2-(methyloxy)phenyl]-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino}-6-methyl-1H-indazol-1-yl)benzoateYield 43.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

2-{2-[5-Fluoro-2-(methyloxy)phenyl]-2-methylpropyl}-2-(trifluoromethyl)oxirane (which may be prepared according to WO 04/063163, 96 mg, 0.33 mmol), methyl 3-(4-amino-6-methyl-1H-indazol-1-yl)benzoate (85 mg, 0.3 mmol) and ytterbium trifluoromethanesulfonate (28 mg, 0.045 mmol) were stirred in acetonitrile (0.4 mL) with some molecular sieves. The resulting mixture was then heated to reflux (80° C.) overnight and then allowed to cool to room temperature. The mixture was poured into ethyl acetate (5 mL) and washed successively with saturated aqueous sodium bicarbonate and aqueous brine. The organic phase was separated, dried over anhydrous sodium sulphate and then concentrated and the residue purified by silica gel column chromatography (10% ethyl acetate in cyclohexane) to give the title compound as a white solid (75 mg).

Workup

  1. temperatureThe resulting mixture was then heated
  2. temperatureto cool to room temperature
  3. washwashed successively with saturated aqueous sodium bicarbonate and aqueous brine
  4. customThe organic phase was separated
  5. dry with materialdried over anhydrous sodium sulphate
  6. concentrationconcentrated
  7. customthe residue purified by silica gel column chromatography (10% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-aa01a0c94d6b42c88d320a15a97ca443
Source dataset
uspto-grants-2012_05
Patent number
US08178573B2

Reaction notes

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