Cesium carbonate → tert-butyl N-[4-[3-[4-(diethoxyphosphorylmethoxy)-2,6-dimethylphenyl]phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

HRID 723227Notes

Reaction equation

HRID 723227 reaction equation
[C:1]([O:5][C:6](=[O:35])[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][C:27]([OH:31])=[CH:26][C:25]=3[CH3:32])[CH:21]=[CH:22][CH:23]=2)(=[O:17])=[O:16])[CH:14]=1)=[NH:9])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].[CH2:42]([O:44][P:45]([CH2:50]OS(C(F)(F)F)(=O)=O)([O:47][CH2:48][CH3:49])=[O:46])[CH3:43]>CN(C=O)C>[CH2:42]([O:44][P:45]([CH2:50][O:31][C:27]1[CH:26]=[C:25]([CH3:32])[C:24]([C:20]2[CH:21]=[CH:22][CH:23]=[C:18]([S:15]([C:13]3[CH:14]=[C:10]([C:8]([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:35])=[NH:9])[S:11][C:12]=3[S:33][CH3:34])(=[O:17])=[O:16])[CH:19]=2)=[C:29]([CH3:30])[CH:28]=1)(=[O:46])[O:47][CH2:48][CH3:49])[CH3:43]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11833487(Diethoxyphosphoryl)methyl trifluoromethanesulfonateHCID 145857620tert-butyl N-[4-[3-(4-hydroxy-2,6-dimethylphenyl)phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

Product 1

HCID 145857608tert-butyl N-[4-[3-[4-(diethoxyphosphorylmethoxy)-2,6-dimethylphenyl]phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamateYield 33%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a flask containing {[4-(4′-hydroxy-2′,6′-dimethyl-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester ((Example 224: step b) 233 mg, 0.42 mmol), Cs2CO3 (137 mg, 0.42 mmol), DMF (2 mL), and trifluoro-methanesulfonic acid diethoxy-phosphorylmethyl ester (200 mg, 0.67 mmol, (Xu, Y. et al J. Org. Chem. 61, 7697 (1996); Phillion, D. et al Tetrahedron Lett. 27, 1477 (1986)) were added and heated to 50 C. This mixture was heated and stirred for 18 h under an Ar atmosphere. DMF was removed under vacuum and the residue was taken in EtOAc and washed with water and saturated NaCl. The EtOAc layer was separated dried over Na2SO4 and evaporated under vacuum to give an oil. This was purified by preparative thin-layer chromatography (EtOAc/Hexane) to give 94 mg (33%) of {3′-[5-(tert-butoxycarbonylamino-imino-methyl)-2-methylsulfanyl-thiophene-3-sulfonyl]-2,6-dimethyl-biphenyl-4-yloxymethyl}-phosphonic acid diethyl ester as a white solid. This solid was dissolved in dichloromethane (2 mL), and cooled in an ice bath. To this iodotrimethylsilane (Aldrich Chemical Company, 60 μL) was added and the mixture was stirred for 1 h at which time the dichloromethane was removed and the residue was taken in MeOH and treated with 6N HCl. This mixture was stirred for 3 h and the solvents were removed under high vacuum. To this residue a 50% solution of TFA in dichloromethane was added and the mixture was stirred for 1 h. TFA and dichloromethane were removed under vacuum and the residue was purified by preparative HPLC (Rev. Phase acetonitrile/water) which yielded the title compound as a white solid (30 mg, 33%). 1H-NMR (CD3OD): δ 7.8–7.7 (m, 2H), 7.62 (s, 1H), 7.5–7.3 (m, 2H), 6.7 (s, 2H), 3.77 (d, 2H, J=9.8 Hz), 2.44 (s, 3H), 1.74 (s, 6H). ESI-MS (m/z): Calcd. for C21H23N2O6PS3: 527.1 (M+H); found: 527.1.

Workup

  1. additionwere added
  2. temperatureheated to 50 C
  3. temperatureThis mixture was heated
  4. customDMF was removed under vacuum
  5. washwashed with water and saturated NaCl
  6. customThe EtOAc layer was separated
  7. dry with materialdried over Na2SO4
  8. customevaporated under vacuum
  9. customto give an oil
  10. customThis was purified by preparative thin-layer chromatography (EtOAc/Hexane)

Sources & evidence

ORD record
ord-2a6220463f1e4844b768dea391ff2195
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Reaction notes

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