Iodoethane → 3-Amino-5-chloro-6-ethoxy-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamide

HRID 656667Notes

Reaction equation

HRID 656667 reaction equation
[H-].[Na+].[CH:3]1([NH:6][C:7]([C:9]2[S:20][C:12]3=[N:13][C:14]([OH:19])=[C:15]([Cl:18])[C:16]([CH3:17])=[C:11]3[C:10]=2[NH2:21])=[O:8])[CH2:5][CH2:4]1.[Br-].[Li+].[CH2:24](I)[CH3:25]>COCCOC.CN(C=O)C>[CH:3]1([NH:6][C:7]([C:9]2[S:20][C:12]3=[N:13][C:14]([O:19][CH2:24][CH3:25])=[C:15]([Cl:18])[C:16]([CH3:17])=[C:11]3[C:10]=2[NH2:21])=[O:8])[CH2:5][CH2:4]1

Participants

7

Reactant 4

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 82050Lithium BromideHCID 178427959HCID 178427959, compound

Product 1

HCID 576644183-Amino-5-chloro-6-ethoxy-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamideYield 8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (0.037 g, 0.925 mmol) is suspended in anhydrous 1,2-dimethoxy-ethane (5.0 ml) under nitrogen. The suspension is cooled to 0° C. To this cold suspension is added via cannula a solution of 3-amino-5-chloro-6-hydroxy-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamide (0.300 g, 1.01 mmol) in anhydrous DMF (5.0 ml). The ice bath is removed, and the reaction is warmed to room temperature. After the reaction is stirred 25 minutes at room temperature, lithium bromide (0.175 g, 2.02 mmol) is added as a solid, and the reaction is stirred for an additional two hours. Finally, ethyl iodide is added (0.24 ml, 0.47 g, 3.00 mmol), and the reaction is stirred for 36 hours at room temperature. At the completion of the reaction time, the mixture is quenched with water. The solid is collected by filtration, then purified by flash chromatography (hexanes:EtOAc gradient) to give the title compound as a white solid (24.3 mg, 8% yield). Mass (m/z): 326.0 (M+), 324.0 (M−).

Workup

  1. customThe ice bath is removed
  2. temperaturethe reaction is warmed to room temperature
  3. stirringthe reaction is stirred for an additional two hours
  4. stirringthe reaction is stirred for 36 hours at room temperature
  5. customAt the completion of the reaction time, the mixture is quenched with water
  6. filtrationThe solid is collected by filtration
  7. custompurified by flash chromatography (hexanes:EtOAc gradient)

Sources & evidence

ORD record
ord-608b0980aa8a46baa00e53d2698321f4
Source dataset
uspto-grants-2011_12
Patent number
US08071776B2

Reaction notes

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