Methyl morpholine oxide → HCID 16223129, compound

HRID 1717560Notes

Reaction equation

HRID 1717560 reaction equation
[F:1][C:2]1[C:3]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([I:29])=[CH:25][C:24]=2[F:30])=[C:4]([C:9]([N:11]2[CH2:14][C:13]([OH:21])([C:15]([NH:17]CC=C)=[O:16])[CH2:12]2)=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].C[N+]1([O-])CC[O:35]CC1.[CH3:39][C:40]([CH3:42])=[O:41].O>[Os](=O)(=O)(=O)=O>[F:1][C:2]1[C:3]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([I:29])=[CH:25][C:24]=2[F:30])=[C:4]([C:9]([N:11]2[CH2:14][C:13]([OH:21])([C:15]([NH:17][CH2:39][CH:40]([OH:41])[CH2:42][OH:35])=[O:16])[CH2:12]2)=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

5

Reactant 3

HCID 82029Methyl morpholine oxideHCID 16223128HCID 16223128, compoundHCID 18366337Propan-2-one--water (1/1)

Product 1

HCID 16223129HCID 16223129, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 30318Osmium TetroxideCatalyst

Procedure

1-({3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxy-N-prop-2-en-1-ylazetidine-3-carboxamide (88 mg, 0.166 mmol) and 4-methylmorpholine N-oxide (58 mg, 0.496 mmol) were dissolved in acetone/water (4:1; 10 mL) and osmium tetroxide (2.5 wt. % in water; 0.1 mL) was added. The solution was stirred at ambient for 15 h, then was quenched with saturated sodium bisulfite (2 mL) and concentrated in vacuo. The residue was partitioned between ethyl acetate and brine. The aqueous portion was extracted with ethyl acetate. The combined organic portion was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification by reverse phase HPLC gave 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-(2,3-dihydroxypropyl)-3-hydroxyazetidine-3-carboxamide (68 mg, 0.120 mmol, 72% yield): 1H NMR (400 MHz, d6-DMSO): 8.65 (br s, 1H), 7.72 (t, 1H), 7.58 (dd, 1H), 7.41-7.36 (m, 1H), 7.34-7.28 (m, 1H), 7.21-7.12 (m, 1H), 6.92 (br s, 1H), 6.72 (ddd, 1H), 5.00-4.10 (br, 2H), 5.10-4.99 (m, 2H), 4.39 (d, 1H), 4.20 (d, 1H), 4.02 (d, 1H), 3.54-3.45 (m, 1H), 3.34-3.21 (m, 2H), 3.06-2.96 (m, 1H); MS (EI) for C20H19F3IN3O5: 566 (MH+).

Workup

  1. customwas quenched with saturated sodium bisulfite (2 mL)
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between ethyl acetate and brine
  4. extractionThe aqueous portion was extracted with ethyl acetate
  5. washThe combined organic portion was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by reverse phase HPLC

Sources & evidence

ORD record
ord-6e05f86e396b4ad6b25d6c5c1bf00140
Source dataset
uspto-grants-2010_09
Patent number
US07803839B2

Reaction notes

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