Tetraethyl methylenediphosphonate → Z-{2-[3'-(5-Carbamimidoyl-2-methylsulfanyl-thiophene-3-sulfonyl)-6-methyl-biphenyl-2-yl]-vinyl}-phosphonic acid trifluoroacetate

HRID 723184Notes

Reaction equation

HRID 723184 reaction equation
C(OC(=O)[NH:7][C:8]([C:10]1[S:11][C:12]([S:33][CH3:34])=[C:13]([S:15]([C:18]2[CH:19]=[C:20]([C:24]3[C:29]([CH3:30])=[CH:28][CH:27]=[CH:26][C:25]=3[CH2:31]O)[CH:21]=[CH:22][CH:23]=2)(=[O:17])=[O:16])[CH:14]=1)=[NH:9])(C)(C)C.C(OP([CH2:44][P:45]([O:50]CC)([O:47]CC)=[O:46])(=O)OCC)C.[H-].[Na+].C(Cl)(Cl)Cl.[F:59][C:60]([F:65])([F:64])[C:61]([OH:63])=[O:62]>ClCCl.C1COCC1.[O-2].[O-2].[Mn+4]>[F:59][C:60]([F:65])([F:64])[C:61]([OH:63])=[O:62].[C:8]([C:10]1[S:11][C:12]([S:33][CH3:34])=[C:13]([S:15]([C:18]2[CH:19]=[C:20]([C:24]3[C:29]([CH3:30])=[CH:28][CH:27]=[CH:26][C:25]=3/[CH:31]=[CH:44]\[P:45](=[O:46])([OH:47])[OH:50])[CH:21]=[CH:22][CH:23]=2)(=[O:16])=[O:17])[CH:14]=1)(=[NH:7])[NH2:9]

Participants

8

Reactant 4

HCID 15455Tetraethyl methylenediphosphonateHCID 24758Sodium hydrideHCID 19978452Chloroform trifluoroacetic acidHCID 145857676tert-butyl N-[4-[3-[2-(hydroxymethyl)-6-methylphenyl]phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

Product 1

HCID 86590795Z-{2-[3'-(5-Carbamimidoyl-2-methylsulfanyl-thiophene-3-sulfonyl)-6-methyl-biphenyl-2-yl]-vinyl}-phosphonic acid trifluoroacetateYield 57%

Reagents, catalysts & solvents 3

HCID 178418406HCID 178418406, compoundCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Manganese dioxide (0.041 g, 0.470 mmol) was added to a solution of ({[4-(2′-hydroxymethyl-6′-methyl-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester (0.025 g, 0.047 mmol) [example 213, step b] in dichloromethane [5 mL] and refluxed for 3 hours. The reaction was filtered through Celite and evaporated. The crude residue was dissolved in anhydrous THF [2 mL] and added to a solution of (diethoxy-phosphorylmethyl)-phosphonic acid diethyl ester (0.011 g, 0.061 mmol) and sodium hydride (0.003 g, 0.056 mmol) in THF [2 mL] at room temperature and stirred for 0.5 hours. A solution of 1N NaOH/MeOH (1/1) [10 mL] was added and the crude product was extracted with ether, dried with magnesium sulfate and evaporated. Column chromatography (50% EtOAc in hexanes) of the residue yielded the title compound (0.019 g, 57%) as a solid. ESI-MS (m/z): Calcd. for C30H37N2O7PS3: 664.15; found: 664.8.

Workup

  1. temperaturerefluxed for 3 hours
  2. filtrationThe reaction was filtered through Celite
  3. customevaporated
  4. dissolutionThe crude residue was dissolved in anhydrous THF [2 mL]
  5. extractionthe crude product was extracted with ether
  6. dry with materialdried with magnesium sulfate
  7. customevaporated

Sources & evidence

ORD record
ord-93c13355ed8149cbb47466ca839b9d17
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Reaction notes

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