Sodium Iodide → 3-(2-Fluoro-4-iodo-phenylamino)-thieno[2,3-c]pyridine-2-carboxylic acid ethyl ester

HRID 1366774Notes

Reaction equation

HRID 1366774 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:14][C:13]2[CH:12]=CN=[CH:9][C:8]=2[C:7]=1[NH:15][C:16]1[CH:21]=[CH:20][C:19](Br)=[CH:18][C:17]=1[F:23])=[O:5])[CH3:2].[I-:24].[Na+].CN[C@@H]1CCCC[C@H]1[NH:34][CH3:35]>O1CCOCC1.[Cu]I>[CH2:1]([O:3][C:4]([C:6]1[S:14][C:13]2=[CH:12][N:34]=[CH:35][CH:9]=[C:8]2[C:7]=1[NH:15][C:16]1[CH:21]=[CH:20][C:19]([I:24])=[CH:18][C:17]=1[F:23])=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 5238Sodium IodideHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamine2×HCID 597038743-(4-Bromo-2-fluoro-phenylamino)-thieno[3,2-c]pyridine-2-carboxylic acid ethyl ester

Product 1

HCID 597039023-(2-Fluoro-4-iodo-phenylamino)-thieno[2,3-c]pyridine-2-carboxylic acid ethyl esterYield 742.4%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 3-(4-bromo-2-fluoro-phenylamino)-thieno[3,2-c]pyridine-2-carboxylic acid ethyl ester (209 mg, 0.53 mmol), copper (1) iodide (5 mg, 0.026 mmol), sodium iodide (159 mg, 1.06 mmol) and trans-N,N′-dimethyl-1,2-cyclohexane diamine (8.5 g, 0.053 mmol) in 1,4-dioxane (1.0 ml) was heated at 105° C. for 24 hours under an argon atmosphere. Copper (1) iodide (5 mg, 0.026 mmol) and trans-N,N′-dimethyl-1,2-cyclohexane diamine (8.5 μl, 0.053 mmol) were added and heating continued for a further 24 h. Once the reaction was cooled to room temperature, the mixture was partitioned between ethyl acetate (30 ml) and 10% v/v 0.880 ammonia/water (20 ml). The layers were separated and the aqueous phase was extracted with DCM (30 ml). The combined organic layer was dried over sodium sulphate, filtered and evaporated then the residue was purified by flash chromatography a Si-SPE (eluting with pentane:diethyl ether, gradient 90:10 to 70:30) to afford the title compound as a yellow solid (174 mg, 74%). LCMS (method B): RT=3.97 min, M+H+=443.

Workup

  1. temperatureheating
  2. temperatureOnce the reaction was cooled to room temperature
  3. customthe mixture was partitioned between ethyl acetate (30 ml) and 10% v/v 0.880 ammonia/water (20 ml)
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with DCM (30 ml)
  6. dry with materialThe combined organic layer was dried over sodium sulphate
  7. filtrationfiltered
  8. customevaporated
  9. customthe residue was purified by flash chromatography a Si-SPE (eluting with pentane:diethyl ether, gradient 90:10 to 70:30)

Sources & evidence

ORD record
ord-6cebf7837a864393a668b50a9c27a9f8
Source dataset
uspto-grants-2011_02
Patent number
US07893085B2

Reaction notes

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