Iodoethane → 2-{[6-(Ethoxymethyl)pyridin-2-yl]amino}-5-[2-fluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide

HRID 385872Notes

Reaction equation

HRID 385872 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[C:8]([C:10]([OH:13])([CH3:12])[CH3:11])[CH:7]=[CH:6][C:5]=1[C:14]1[S:18][C:17]([NH:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][OH:27])[N:21]=2)=[C:16]([C:28]([NH2:30])=[O:29])[CH:15]=1.I[CH2:32][CH3:33]>CN(C=O)C>[CH2:32]([O:27][CH2:26][C:22]1[N:21]=[C:20]([NH:19][C:17]2[S:18][C:14]([C:5]3[CH:6]=[CH:7][C:8]([C:10]([OH:13])([CH3:11])[CH3:12])=[CH:9][C:4]=3[F:3])=[CH:15][C:16]=2[C:28]([NH2:30])=[O:29])[CH:25]=[CH:24][CH:23]=1)[CH3:33]

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 251234855-(2-Fluoro-4-(1-hydroxy-1-methylethyl)phenyl)-2-((6-(hydroxymethyl)-2-pyridinyl)amino)-3-thiophenecarboxamide

Product 1

HCID 595256452-{[6-(Ethoxymethyl)pyridin-2-yl]amino}-5-[2-fluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of NaH (10 mg, 0.25 mmol) in DMF (1.25 mL) at 0° C. under argon was added 5-[2-fluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-{[6-(hydroxymethyl)pyridin-2-yl]amino}thiophene-3-carboxamide (Example 48) (50 mg, 0.125 mmol) and the mixture was allowed to stir for 20 minutes. Iodoethane (29 mg, 0.19 mmol) was then added and the reaction was allowed to warm to room temperature and subsequently heated to 60° C. overnight. The reaction was cooled to ambient temperature, quenched by the addition of water, extracted with ethyl acetate and concentrated in vacuo. The crude residue was reverse phase HPLC (acteonitrile/water with formic acid as a modifier) to afford the title compound.

Workup

  1. temperaturesubsequently heated to 60° C. overnight
  2. temperatureThe reaction was cooled to ambient temperature
  3. customquenched by the addition of water
  4. extractionextracted with ethyl acetate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f48db02f2b4c49f5b7bf837c5aee85ae
Source dataset
uspto-grants-2013_02
Patent number
US08367706B2

Reaction notes

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