Cesium carbonate → (1R,2S)-1-(3-ethylphenyl)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)propan-2-amine hydrochloride

HRID 13027

Reaction equation

HRID 13027 reaction equation
[ClH:1].[NH2:2][C@@H:3]([CH3:14])[C@@H:4]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][CH3:13])[CH:7]=1)[OH:5].[F:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]2[C:30]3[C:25](=[CH:26][C:27](I)=[CH:28][CH:29]=3)[CH:24]=[N:23]2)=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)CCC.[Cu]I>[ClH:1].[CH2:12]([C:8]1[CH:7]=[C:6]([C@@H:4]([O:5][C:27]2[CH:26]=[C:25]3[C:30](=[CH:29][CH:28]=2)[N:22]([C:19]2[CH:20]=[CH:21][C:16]([F:15])=[CH:17][CH:18]=2)[N:23]=[CH:24]3)[C@@H:3]([NH2:2])[CH3:14])[CH:11]=[CH:10][CH:9]=1)[CH3:13]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 592511281-(4-fluorophenyl)-5-iodo-1H-indazoleHCID 66812822(1R,2S)-2-amino-1-(3-ethylphenyl)propan-1-ol hydrochloride

Product 1

HCID 66812954(1R,2S)-1-(3-ethylphenyl)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)propan-2-amine hydrochloride

Reagents, catalysts & solvents 2

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

Procedure

The subtitle compound was prepared analogous to the method described in Example 19 (step 19a). A mixture of (1R,2S)-2-amino-1-(3-ethylphenyl)propan-1-ol hydrochloride (22b, 216 mg, 1.00 mmol), 1-(4-fluorophenyl)-5-iodo-1H-indazole (406 mg, 1.20 mmol), cesium carbonate (979 mg, 3.00 mmol) and copper(I) iodide (38.1 mg, 0.20 mmol) in butyronitrile (3 mL) was heated for 19 h at +125° C. in a sealed reactiontube flushed with Argon. After final purification by HPLC the obtained material was dissolved in tert-Butyl methyl ether, and precipitated as the hydrochloride salt by adding a solution of 6-7 N HCl in 2-propanol. Yield 199 mg (46%)

Workup

  1. temperaturewas heated for 19 h at +125° C. in a sealed reactiontube
  2. customflushed with Argon
  3. customAfter final purification by HPLC the obtained material
  4. dissolutionwas dissolved in tert-Butyl methyl ether
  5. customprecipitated as the hydrochloride salt
  6. additionby adding a solution of 6-7 N HCl in 2-propanol

Sources & evidence

ORD record
ord-f12e6cf132d1494ba1297c9c561f0231
Source dataset
uspto-grants-2010_06
Patent number
US07728030B2

Linked notes

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