Phenylpropanolamine → (1R,2S)-1-[(1-isopropyl-1H-indazol-5-yl)oxy]-1-phenylpropan-2-amine

HRID 13158

Reaction equation

HRID 13158 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]([CH3:13])[CH3:12])[N:6]=[CH:5]2.[NH2:14][C@@H:15]([CH3:24])[C@@H:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[OH:17].C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)CCC.[Cu]I>[CH:11]([N:7]1[C:8]2[C:4](=[CH:3][C:2]([O:17][C@H:16]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C@@H:15]([NH2:14])[CH3:24])=[CH:10][CH:9]=2)[CH:5]=[N:6]1)([CH3:13])[CH3:12]

Participants

6

Reactant 3

HCID 10297PhenylpropanolamineHCID 10796Cesium carbonateHCID 593398645-iodo-1-isopropyl-1H-indazole

Product 1

HCID 59339639(1R,2S)-1-[(1-isopropyl-1H-indazol-5-yl)oxy]-1-phenylpropan-2-amine

Reagents, catalysts & solvents 2

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

Conditions

Temperature
125 °C

Procedure

A mixture of 5-iodo-1-isopropyl-1H-indazole (129c, 461 mg, 1.26 mmol), (1R,2S)-2-amino-1-phenylpropan-1-ol (286 mg, 1.89 mmol), copper (I) iodide (25 mg, 130 μmol), and cesium carbonate (1.45 g, 3.8 mmol) in butyronitrile (5 ml) was stirred at 125° C. for 2 h. Then the mixture was cooled to r.t., the inorganic material was removed by filtration and washed with ethyl acetete. The combined organic solutions were concentrated in vacuo, and the product purified by flash chromatography on silica gel (ethyl acetate/methanol). Yield 200 mg (51%) of a brown oil.

Workup

  1. temperatureThen the mixture was cooled to r.t.
  2. customthe inorganic material was removed by filtration
  3. washwashed with ethyl acetete
  4. concentrationThe combined organic solutions were concentrated in vacuo
  5. customthe product purified by flash chromatography on silica gel (ethyl acetate/methanol)

Sources & evidence

ORD record
ord-36e1dcf13e4e41959da051f6f8d727ca
Source dataset
uspto-grants-2010_06
Patent number
US07728030B2

Linked notes

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