O-(3-Methylsulfanyl-propyl)-hydroxylamine → 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-5-[(E)-3-methylsulfanylpropoxyiminomethyl]benzamide

HRID 2038606Notes

Reaction equation

HRID 2038606 reaction equation
[F:1][C:2]1[C:3]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=2[F:26])=[C:4]([CH:12]=[C:13]([CH:16]=O)[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6].[CH3:27][S:28][CH2:29][CH2:30][CH2:31][O:32][NH2:33]>C(Cl)Cl.CO>[F:1][C:2]1[C:3]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=2[F:26])=[C:4]([CH:12]=[C:13](/[CH:16]=[N:33]/[O:32][CH2:31][CH2:30][CH2:29][S:28][CH3:27])[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6]

Participants

5

Reactant 2

HCID 21114240O-(3-Methylsulfanyl-propyl)-hydroxylamineHCID 231323883,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-formyl-N-(2-hydroxy-ethoxy)-benzamide

Product 1

HCID 593480253,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-5-[(E)-3-methylsulfanylpropoxyiminomethyl]benzamideYield 96%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

The title compound was obtained by a procedure similar to that in Step B of Example 9 using 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-formyl-N-(2-hydroxy-ethoxy)-benzamide obtained in Step F of Example 1 as a starting material and O-(3-methylsulfanyl-propyl)-hydroxylamine obtained in Step B as a reagent. Namely, 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-formyl-N-(2-hydroxy-ethoxy)-benzamide (76 mg, 0.158 mmol) was dissolved in a mixed solvent of methylene chloride (5 mL) and methanol (1 mL). O-(3-Methylsulfanyl-propyl)-hydroxylamine (100 μL) was added thereto, and the mixture was stirred at room temperature for 3 hours. After completion of the reaction, the solvent was evaporated under reduced pressure to give a pale yellow crude product. The residue was triturated with a proper amount of ethyl acetate:hexane (1:9) to give (E)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(3-methylsulfanyl-propoxyimino)-methyl]-benzamide (88.8 mg, 96%) as a white solid.

Workup

  1. customAfter completion of the reaction
  2. customthe solvent was evaporated under reduced pressure
  3. customto give a pale yellow crude product
  4. customThe residue was triturated with a proper amount of ethyl acetate:hexane (1:9)

Sources & evidence

ORD record
ord-0d5e56fc8d9a40d38c75d2f1a34d43e1
Source dataset
uspto-grants-2013_11
Patent number
US08575391B2

Reaction notes

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