Dimethylsulfoxide ethyl acetate → Diethyl 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)-1,1-difluoro-2-oxoethylphosphonate

HRID 2167650Notes

Reaction equation

HRID 2167650 reaction equation
[NH2:1][C:2]1[C:11]2[N:10]=[CH:9][C:8]([CH2:12][CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=3[CH3:22])=[CH:7][C:6]=2[C:5]2[CH:23]=[CH:24][C:25]([CH:27]([OH:39])[C:28]([P:31](=[O:38])([O:35][CH2:36][CH3:37])[O:32][CH2:33][CH3:34])([F:30])[F:29])=[CH:26][C:4]=2[N:3]=1.CS(C)=O.C(OCC)(=O)C>C(OCC)(=O)C>[NH2:1][C:2]1[C:11]2[N:10]=[CH:9][C:8]([CH2:12][CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=3[CH3:22])=[CH:7][C:6]=2[C:5]2[CH:23]=[CH:24][C:25]([C:27](=[O:39])[C:28]([P:31](=[O:38])([O:35][CH2:36][CH3:37])[O:32][CH2:33][CH3:34])([F:29])[F:30])=[CH:26][C:4]=2[N:3]=1

Participants

4

Reactant 2

HCID 23053668Dimethylsulfoxide ethyl acetateHCID 86651451Diethyl 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)-1,1-difluoro-2-hydroxyethylphosphonate

Product 1

HCID 86651452Diethyl 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)-1,1-difluoro-2-oxoethylphosphonate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of diethyl 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)-1,1-difluoro-2-hydroxyethylphosphonate (2-3) (1.0 equiv.) in 1:1 DMSO/ethyl acetate (0.07 M) was added IBX (1.5 equiv.). The reaction was heated to 80° C. for 1 hour, and then cooled to room temperature. The mixture was diluted with ethyl acetate and filtered through celite. The filtrate was washed with water (2×), brine, dried over anhydrous MgSO4, and concentrated in vacuo. The resulting residue was purified by a COMBIFLASH® system (ISCO) using a gradient of 0-5% MeOH/DCM to provide diethyl 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)-1,1-difluoro-2-oxoethylphosphonate (2-4) as a solid.

Workup

  1. temperaturecooled to room temperature
  2. filtrationfiltered through celite
  3. washThe filtrate was washed with water (2×), brine
  4. dry with materialdried over anhydrous MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by a COMBIFLASH® system (ISCO)

Sources & evidence

ORD record
ord-aaecc42059154c1a8722d8c69b369155
Source dataset
uspto-grants-2015_06
Patent number
US09045470B2

Reaction notes

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