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

HRID 1925596Notes

Reaction equation

HRID 1925596 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.C(#N)C.[NH2:24][C:25]1[CH:33]=[C:32]([CH3:34])[CH:31]=[C:30]2[C:26]=1[CH:27]=[N:28][N:29]2[C:35]1[CH:36]=[C:37]([CH:42]=[CH:43][CH:44]=1)[C:38]([O:40][CH3:41])=[O:39]>C(OCC)(=O)C.FC(F)(F)S([O-])(=O)=O.[Y+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O>[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:24][C:25]2[CH:33]=[C:32]([CH3:34])[CH:31]=[C:30]3[C:26]=2[CH:27]=[N:28][N:29]3[C:35]2[CH:36]=[C:37]([CH:42]=[CH:43][CH:44]=2)[C:38]([O:40][CH3:41])=[O:39])[CH:7]=1

Participants

6

Reactant 3

HCID 6342AcetonitrileHCID 11208565(R)-2-[2-(5-Fluoro-2-methoxyphenyl)-2-methylpropyl]-2-trifluoromethyloxiraneHCID 57672644Methyl 3-(4-amino-6-methyl-1H-indazol-1-yl)benzoate

Product 1

HCID 57672637Methyl 3-(4-{[(2R)-4-[5-fluoro-2-(methyloxy)phenyl]-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino}-6-methyl-1H-indazol-1-yl)benzoate

Reagents, catalysts & solvents 2

HCID 2733939Yttrium trifluoromethanesulfonateCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
83 °C

Procedure

(2R)-2-{2-[5-Fluoro-2-(methyloxy)phenyl]-2-methylpropyl}-2-(trifluoromethyl)oxirane (530 mg, 1.81 mmol) was added to acetonitrile (2.5 mL), followed by the addition of methyl 3-(4-amino-6-methyl-1H-indazol-1-yl)benzoate (590 mg, 2.1 mmol) and yttrium trifluoromethanesulfonate (197 mg, 0.37 mmol) at room temperature under a nitrogen atmosphere. The resulting mixture was then heated to reflux (83° C.) overnight, then allowed to cool down to room temperature and diluted with ethyl acetate (7 mL). The mixture was washed successively with saturated sodium bicarbonate (10 mL) and water (10 mL), dried and concentrated. The residue was then purified by column chromatography (10% ethyl acetate in cyclohexane) to give, after concentration, the title compound (540 mg).

Workup

  1. temperatureThe resulting mixture was then heated
  2. temperatureto cool down to room temperature
  3. washThe mixture was washed successively with saturated sodium bicarbonate (10 mL) and water (10 mL)
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was then purified by column chromatography (10% ethyl acetate in cyclohexane)
  7. customto give
  8. concentrationafter concentration

Sources & evidence

ORD record
ord-cdd28021731b454ea0f8b9960d2a1e18
Source dataset
uspto-grants-2012_05
Patent number
US08178573B2

Reaction notes

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