Sodium Iodide → HCID 86633057, compound

HRID 1094187Notes

Reaction equation

HRID 1094187 reaction equation
[CH:1]1([NH:7][C:8]2[CH:17]=[C:16]3[C:11]([C:12](=[O:29])[C:13](/[CH:23]=[CH:24]/[P:25](=[O:28])([OH:27])[OH:26])=[CH:14][N:15]3[CH:18]([CH2:21][CH3:22])[CH2:19][CH3:20])=[CH:10][C:9]=2[F:30])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[I-].[Na+].C1CCN2C(=NCCC2)CC1.[C:44]([O:50][CH2:51]Cl)(=[O:49])[C:45]([CH3:48])([CH3:47])[CH3:46].[Cl-].[NH4+]>C(#N)C.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[C:44]([O:50][CH2:51][O:28][P:25](/[CH:24]=[CH:23]/[C:13]1[C:12](=[O:29])[C:11]2[C:16](=[CH:17][C:8]([NH:7][CH:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)=[C:9]([F:30])[CH:10]=2)[N:15]([CH:18]([CH2:19][CH3:20])[CH2:21][CH3:22])[CH:14]=1)([OH:27])=[O:26])(=[O:49])[C:45]([CH3:48])([CH3:47])[CH3:46]

Participants

8

Reactant 5

HCID 5238Sodium IodideHCID 25517Ammonium ChlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 87885Chloromethyl pivalateHCID 66636857HCID 66636857, compound

Product 1

HCID 86633057HCID 86633057, compound

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

500 mg of {(E)-2-[7-(cyclohexylamino)-1-(1-ethylpropyl)-6-fluoro-4-oxo-1,4-dihydroquinolin-3-yl]vinyl}phosphonic acid was dissolved in 10 ml of acetonitrile, and 86 mg of sodium iodide, 0.51 ml of 1,8-diazabicyclo[5.4.0]-7-undecene, 194 mg of tetrabutylammonium hydrogensulfate and 0.53 ml of chloromethyl pivalate were added in that order, followed by overnight stirring at 80° C. Aqueous saturated ammonium chloride was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with aqueous saturated sodium chloride, dried over anhydrous sodium sulfate and then evaporated under a reduced pressure. By purifying the resulting residue by silica gel column chromatography, 400 mg of bis{[(2,2-dimethylpropanoyl)oxy]methyl}{(E)-2-[7-(cyclohexylamino)-1-(1-ethylpropyl)-6-fluoro-4-oxo-1,4-dihydroquinolin-3-yl]vinyl}phosphonate (Example 25) and 190 mg of {[{(E)-2-[7-(cyclohexylamino)-1-(1-ethylpropyl)-6-fluoro-4-oxo-1,4-dihydro-3-quinolinyl]vinyl}(hydroxy)phosphoryl]oxy}methyl pivalate (Example 26) were obtained.

Workup

  1. extractionfollowed by extraction with chloroform
  2. washThe organic layer was washed with aqueous saturated sodium chloride
  3. dry with materialdried over anhydrous sodium sulfate
  4. customevaporated under a reduced pressure
  5. customBy purifying the resulting residue by silica gel column chromatography, 400 mg of bis{[(2,2-dimethylpropanoyl)oxy]methyl}{(E)-2-[7-(cyclohexylamino)-1-(1-ethylpropyl)-6-fluoro-4-oxo-1,4-dihydroquinolin-3-yl]vinyl}phosphonate (Example 25)

Sources & evidence

ORD record
ord-807d0a9e895441388aaa40d527280516
Source dataset
uspto-grants-2012_03
Patent number
US08133882B2

Reaction notes

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