Cesium carbonate → (4-(5-((1R,2S)-2-amino-1-phenylpropoxy)-1H-indazol-1-yl)phenyl)methanol

HRID 13175Notes

Reaction equation

HRID 13175 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:16]=[CH:15][C:14]([CH2:17][OH:18])=[CH:13][CH:12]=1)[N:6]=[CH:5]2.[C:19](=[O:22])([O-])[O-].[Cs+].[Cs+]>C(#N)CCC.[Cu]I>[NH2:6][C@@H:5]([CH3:4])[C@@H:19]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[O:22][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:16]=[CH:15][C:14]([CH2:17][OH:18])=[CH:13][CH:12]=1)[N:6]=[CH:5]2

Participants

5

Reactant 2

HCID 10796Cesium carbonateHCID 59339895(4-(5-iodo-1H-indazol-1-yl)phenyl)methanol

Product 1

HCID 59339731(4-(5-((1R,2S)-2-amino-1-phenylpropoxy)-1H-indazol-1-yl)phenyl)methanolYield 92.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8008ButyronitrileSolvent

Procedure

(4-(5-iodo-1H-indazol-1-yl)phenyl)methanol (141b, 1.06 g, 3 mmol), (2R,3S-norephedrine (1.39 g, 9.2 mmol), CuI (206 mg, 1 mmol) and was stirred under argon atmosphere in butyronitrile (14 mL) at 125° C. Caesium carbonate (5.1 g, 15.7 mmol) was added and the mixture was vigorously stirred for 50 min, cooled, filtered and evaporated. Chromatography (SiO2, 040% MeOH in EtOAc) afforded (4-(5-((1R,2S)-2-amino-1-phenylpropoxy)-1H-indazol-1-yl)phenyl)methanol (516 mg, 45%).

Workup

  1. temperaturecooled
  2. filtrationfiltered
  3. customevaporated

Sources & evidence

ORD record
ord-047d468f6e8946a4bfb3f06fd742849b
Source dataset
uspto-grants-2010_06
Patent number
US07728030B2

Reaction notes

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