1H-Indazole → ethyl 2-[4-(1H-indazol-1-ylmethyl)phenyl]-1,3-oxazole-4-carboxylate

HRID 1716858Notes

Reaction equation

HRID 1716858 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[H-].[Na+].Cl[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[O:21][CH:22]=[C:23]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:24]=2)=[CH:16][CH:15]=1>CN(C=O)C.CCOC(C)=O>[N:1]1([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:20]3[O:21][CH:22]=[C:23]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:24]=3)=[CH:18][CH:19]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[N:2]1

Participants

6

Reactant 3

HCID 92211H-IndazoleHCID 24758Sodium hydrideHCID 46834790Ethyl 2-[4-(chloromethyl)phenyl]-1,3-oxazole-4-carboxylate

Product 1

HCID 68666190ethyl 2-[4-(1H-indazol-1-ylmethyl)phenyl]-1,3-oxazole-4-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of indazole (0.244 g, 2.07 mmol) in DMF at 0° C. was treated with sodium hydride (0.076 g, 1.98 mmol), stirred for 10 minutes at room temperature, treated with ethyl 2-[4-(chloromethyl)phenyl]-1,3-oxazole-4-carboxylate (0.5 g, 1.88 mmol) and stirred at 80° C. overnight. The reaction mixture was diluted with EtOAc, washed with water, dried over MgSO4 and concentrated in vacuo to give a solid residue. The resultant residue was purified by column chromatography (silica, EtOAc:hexanes, 50%) to give ethyl 2-[4-(1H-indazol-1-ylmethyl)phenyl]-1,3-oxazole-4-carboxylate as white solid. The resulting solid (0.45 g, 1.29 mmol) was dissolved in 1:1 MeOH:THF treated with 1.0 M LiOH for 3 hours at 60° C. and concentrated in in vacuo. The resulting residue was diluted with water, treated with 1.0 M HCl and filtered to afford the title product 92% yield, identified by NMR and mass spectral analyses. LCMS (ESI+) 320 (MH+).

Workup

  1. stirringstirred at 80° C. overnight
  2. washwashed with water
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customto give a solid residue
  6. customThe resultant residue was purified by column chromatography (silica, EtOAc:hexanes, 50%)

Sources & evidence

ORD record
ord-9e9370609dce4468a02189a870097754
Source dataset
uspto-grants-2010_09
Patent number
US07803825B2

Reaction notes

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