Tetrahydrofuran → N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide

HRID 410134Notes

Reaction equation

HRID 410134 reaction equation
[CH2:1]([C:4]1([S:7]([NH:10][C:11]2C(OC)=C[C:14]([F:19])=[C:13]([F:20])[C:12]=2[NH:21][C:22]2[CH:27]=[CH:26][C:25]([I:28])=[CH:24][C:23]=2[F:29])(=[O:9])=[O:8])[CH2:6][CH2:5]1)C=C.C[N+]1([O-])[CH2:36][CH2:35][O:34]CC1.[C:38]([O:41][CH2:42][CH3:43])(=O)C.C1C[O:47]CC1>O.[Os](=O)(=O)(=O)=O>[F:20][C:13]1[C:12]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([I:28])=[CH:24][C:23]=2[F:29])=[C:11]([NH:10][S:7]([C:4]2([CH2:1][CH:36]([OH:47])[CH2:35][OH:34])[CH2:5][CH2:6]2)(=[O:8])=[O:9])[C:42]([O:41][CH3:38])=[CH:43][C:14]=1[F:19]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 8857Ethyl AcetateHCID 82029Methyl morpholine oxideHCID 574300741-Allyl-N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)cyclopropane-1-sulfonamide

Product 1

HCID 15985330N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamideYield 78%

Reagents, catalysts & solvents 2

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolvent

Procedure

1-Allyl-N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)cyclopropane-1-sulfonamide (97 mg, 0.18 mmol) and 4-methylmorpholine N-oxide (21 mg, 0.18 mmol) were dissolved in THF (8 mL). Osmium tetroxide was added at room temperature (0.018 mmol, 0.13 mL, 4% in H2O) and the reaction mixture was stirred at room temperature for 16 hours. Ethyl acetate was added, and the organic phase was washed with water, dried (MgSO4) and concentrated under reduced pressure. The residue was purified over silica gel chromatography (eluants: EtOAc/MeOH) to obtain the titled product (0.80 g, 78%). 1H NMR (CDCl3, 300 MHz): δ 7.38 (dd, J=1.7 & 10.3 Hz, 1H), 7.26 (m, 1H), 7.14 (s, 1H), 6.87 (s, 1H), 6.53 (dd, J=6.8 & 11.4 Hz, 1H), 6.43 (m, 1H), 4.06 (m, 1H), 3.89 (s, 3H), 3.63 (dd, J=3.7 & 11.1 Hz, 1H), 3.49 (dd, J=6.4 & 11.1 Hz, 1H), 2.3 (dd, J=9.7 & 16.1 Hz, 1H), 1.77 (dd, J=1.9 & 16.0 Hz, 1H), 1.37 (m, 1H), 1.25 (m, 1H), 1.21 (m, 2H), 0.86 (m, 2H); m/z=571 [M−1]−.

Workup

  1. washthe organic phase was washed with water
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified over silica gel chromatography (eluants: EtOAc/MeOH)

Sources & evidence

ORD record
ord-b45282fcf42c4233ba3c31e4beb33bd1
Source dataset
uspto-grants-2014_06
Patent number
US08759577B2

Reaction notes

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