Methyl iodide → N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)-N-methyl cyclopropane sulfonamide

HRID 73384Notes

Reaction equation

HRID 73384 reaction equation
[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=2[F:24])=[C:4]([NH:9][S:10]([CH:13]2[CH2:15][CH2:14]2)(=[O:12])=[O:11])[CH:5]=[CH:6][C:7]=1[F:8].[Li+].[CH3:26][Si]([N-][Si](C)(C)C)(C)C.CI>C1COCC1>[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=2[F:24])=[C:4]([N:9]([CH3:26])[S:10]([CH:13]2[CH2:14][CH2:15]2)(=[O:12])=[O:11])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 15602695N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)cyclopropanesulfonamide

Product 1

HCID 53492153N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)-N-methyl cyclopropane sulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)cyclopropane-sulfonamide (see Example 2) (283.9 mg, 0.61 mmol) in 3 ml anhydrous THF was added at −78° C. a IM solution of LHMDS (0.6 ml, 0.6 mol) and the solution was stirred for 10 min at this temperature. Then, methyl iodide (0.8 ml, 1.824 g, 12.9 mmol) was added and the mixture was warmed to room temperature and stirred for 7 h. The solvent was removed and the residue extracted using EtOAc and brine. The organic fractions were dried using Na2SO4 and the solvent was removed. The obtained crude product was purified using flash-column chromatography (Si, EtOAc/Hexanes 1:2, Rf=0.45). Yield: 205 mg, 70%). 1H-NMR (500 MHz, CDCl3): δ=7.41-7.39 (d, 1H, J=10 Hz), 7.30-7.29 (d, 1H, J=8.0 Hz), 7.23-7.20 (m, 1H), 6.98-6.93 (q, 1H, J=8.5 Hz), 6.60 (s, 1H, br), 6.51-6.47 (m, 1H), 3.23 (s, 3H), 2.46-2.42 (m, 1H), 1.19-1.16 (m, 2H), 1.04-1.02 (m, 2H); m/z=481 [M−1]−.

Workup

  1. stirringstirred for 7 h
  2. customThe solvent was removed
  3. extractionthe residue extracted
  4. customThe organic fractions were dried
  5. customthe solvent was removed
  6. customThe obtained crude product
  7. customwas purified

Sources & evidence

ORD record
ord-8a0374834a5d47fb89464834ff37c35a
Source dataset
uspto-grants-2014_09
Patent number
US08829052B2

Reaction notes

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