Sodium hydride → 3-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3H-imidazo[4,5-b]pyridine-2-carboxylic acid methyl ester

HRID 18517Notes

Reaction equation

HRID 18517 reaction equation
[CH3:1][O:2][C:3]([C:5]1[NH:13][C:8]2=[N:9][CH:10]=[CH:11][CH:12]=[C:7]2[N:6]=1)=[O:4].[H-].[Na+].Br[CH2:17][C:18]1[CH:22]=[C:21]([C:23]2[S:24][C:25]([Cl:28])=[CH:26][CH:27]=2)[O:20][N:19]=1>CN(C=O)C.O>[CH3:1][O:2][C:3]([C:5]1[N:13]([CH2:17][C:18]2[CH:22]=[C:21]([C:23]3[S:24][C:25]([Cl:28])=[CH:26][CH:27]=3)[O:20][N:19]=2)[C:8]2=[N:9][CH:10]=[CH:11][CH:12]=[C:7]2[N:6]=1)=[O:4]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 111501463-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazoleHCID 178499037HCID 178499037, compound

Product 1

HCID 686160463-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3H-imidazo[4,5-b]pyridine-2-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 6228DimethylformamideSolvent

Procedure

100 mg (0.56 mmol) 3H-Imidazo[4,5-b]pyridine-2-carboxylic acid methyl ester were dissolved in 3 mL DMF. 22.6 mg (0.56 mmol) sodium hydride (60% in mineral oil) were added and the mixture was stirred 30 minutes at room temperature. 157.2 mg (0.56 mmol) 3-Bromomethyl-5-(5-Chloro-thiophen-2-yl)-isoxazole were added and the resulting mixture was stirred for 1 h at 80° C. The reaction mixture was cooled to room temperature and after the addition of a few drops of water concentrated under reduced pressure. HPLC-MS-analysis showed the presence of another isomer (ratio of isomers≈7:1). Final purification by preparative RP-HPLC (CH3CN/H2O gradient+0.05% formic acid) gave pure 3-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3H-imidazo[4,5-b]pyridine-2-carboxylic acid methyl ester as a brown amorphous solid.

Workup

  1. stirringthe resulting mixture was stirred for 1 h at 80° C
  2. temperatureThe reaction mixture was cooled to room temperature
  3. concentrationconcentrated under reduced pressure
  4. customFinal purification by preparative RP-HPLC (CH3CN/H2O gradient+0.05% formic acid)

Sources & evidence

ORD record
ord-e07c0f1301ec46ce86bb863518609d58
Source dataset
uspto-grants-2010_06
Patent number
US07741341B2

Reaction notes

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