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

HRID 1259476Notes

Reaction equation

HRID 1259476 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-ae4e36877e3f467ca125c226cb00c87c
Source dataset
uspto-grants-2013_06
Patent number
US08466316B2

Reaction notes

Loading…