Water → N-(4,5-Difluoro-6-(2-fluoro-4-iodophenylamino)benzo[d]oxazol-7-yl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide

HRID 1914905Notes

Reaction equation

HRID 1914905 reaction equation
C[N+:2]1([O-])[CH2:7][CH2:6][O:5][CH2:4]C1.[F:9][C:10]1C2N=COC=2[C:13]([NH:19][S:20]([C:23]2([CH2:26]C=C)[CH2:25][CH2:24]2)(=[O:22])=[O:21])=[C:12]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([I:36])=[CH:32][C:31]=2[F:37])[C:11]=1[F:38].[OH2:39].[CH2:40]1[CH2:44][O:43]CC1>[Os](=O)(=O)(=O)=O>[F:9][C:10]1[C:7]2[N:2]=[CH:4][O:5][C:6]=2[C:13]([NH:19][S:20]([C:23]2([CH2:26][CH:40]([OH:39])[CH2:44][OH:43])[CH2:25][CH2:24]2)(=[O:21])=[O:22])=[C:12]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([I:36])=[CH:32][C:31]=2[F:37])[C:11]=1[F:38]

Participants

6

Reactant 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 82029Methyl morpholine oxideHCID 532415631-Allyl-cyclopropanesulfonic acid [4,5-difluoro-6-(2-fluoro-4-iodo-phenylamino)-benzooxazol-7-yl]-amide

Product 1

HCID 53241564N-(4,5-Difluoro-6-(2-fluoro-4-iodophenylamino)benzo[d]oxazol-7-yl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamideYield 17.7%

Reagents, catalysts & solvents 1

HCID 30318Osmium TetroxideCatalyst

Procedure

N-Methylmorpholine-N-oxide (34 mg, 0.290 mmol) was added to a solution of 1-allyl-cyclopropanesulfonic acid [4,5-difluoro-6-(2-fluoro-4-iodo-phenylamino)-benzooxazol-7-yl]-amide (1D: 160 mg, 0.290 mmol) in THF (10 mL). This was followed by the addition of osmium tetroxide (7.3 mg, 0.0287 mmol) and water (0.5 mL). The resulting mixture was stirred at room temperature overnight. The reaction mixture was concentrated and diluted with ethyl acetate. The organic layer was washed with water, saturated NaHCO3, brine, dried over anhydrous Na2SO4 and concentrated to afford 150 mg of the crude product. Purification by preparative HPLC, followed by preparative TLC afforded 8 mg of the product (17.7% yield). H1NMR (CDCl3, 300 MHz): δ 8.14 (s, 1H), 7.94 (s, 1H), 7.46-7.36 (m, 1H), 7.3-7.2 (m, 1H), 6.82 (s, 1H), 6.45-6.34 (m, 1H), 4.40-4.26 (m, 2H), 4.20-4.10 (m, 1H), 3.75-3.65 (m, 1H), 3.60-3.50 (m, 1H), 2.62-2.50 (m, 2H), 0.92-0.80 (m, 4H). LCMS: 96.11%, m/z=581.9 (M-1). HPLC: 94.29%.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with ethyl acetate
  3. washThe organic layer was washed with water, saturated NaHCO3, brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. customto afford 150 mg of the crude product
  7. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-5d8e2edfcdd544908035b14fb10f7d74
Source dataset
uspto-grants-2013_12
Patent number
US08614239B2

Reaction notes

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