Cesium carbonate → {[3'-(5-Carbamimidoyl-2-methylsulfanyl-thiophene-3-sulfonyl)-2-methyl-biphenyl-4-ylamino]-methyl}-phosphonic acid

HRID 723134Notes

Reaction equation

HRID 723134 reaction equation
C(OC(=O)[NH:7][C:8]([C:10]1[S:11][C:12]([S:32][CH3:33])=[C:13]([S:15]([C:18]2[CH:19]=[C:20]([C:24]3[CH:29]=[CH:28][C:27]([NH2:30])=[CH:26][C:25]=3[CH3:31])[CH:21]=[CH:22][CH:23]=2)(=[O:17])=[O:16])[CH:14]=1)=[NH:9])(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].C([O:43][P:44]([CH2:49]OS(C(F)(F)F)(=O)=O)([O:46]CC)=[O:45])C>CN(C)C(=O)C>[C:8]([C:10]1[S:11][C:12]([S:32][CH3:33])=[C:13]([S:15]([C:18]2[CH:19]=[C:20]([C:24]3[CH:29]=[CH:28][C:27]([NH:30][CH2:49][P:44](=[O:43])([OH:46])[OH:45])=[CH:26][C:25]=3[CH3:31])[CH:21]=[CH:22][CH:23]=2)(=[O:16])=[O:17])[CH:14]=1)(=[NH:9])[NH2:7]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11833487(Diethoxyphosphoryl)methyl trifluoromethanesulfonate2×HCID 145857675tert-butyl N-[4-[3-(4-amino-2-methylphenyl)phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

Product 1

HCID 21886119{[3'-(5-Carbamimidoyl-2-methylsulfanyl-thiophene-3-sulfonyl)-2-methyl-biphenyl-4-ylamino]-methyl}-phosphonic acidYield 128.1%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of {[4-(4′-amino-2′-methyl-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester (30 mg, 58.0 μmol), as prepared according to the procedure of step b of Example 120, cesium carbonate (19 mg, 58 μmol), and N,N-dimethylacetamide (0.4 mL) was added a solution of trifluoro-methanesulfonic acid diethoxy-phosphorylmethyl ester (18 mg, 58 μmol) (Xu, Y. et al, J. Org. Chem. 61, 7697 (1996); Phimon, D. et al, Tetrahedron Lett. 27, 1477 (1986)), and heated at 50° C. for 48 h. Additional trifluoro-methanesulfonic acid diethoxy-phosphorylmethyl ester (18 mg, 58 μmol) was added. The mixture was heated at 50° C. for additional 24 h. Solvent was evaporated. The resulting mixture was partitioned between DCM and H2O. Aqueous layer was separated and extracted with DCM. All the DCM layers were combined, washed with H2O and brine, dried over Na2SO4, concentrated, and flash chromatographed on silica gel column, eluting with EtOAc/DCM (20 and 30%) to give the title compound (38 mg, 98% yield) as an orange oil. 1H NMR (CDCl3): δ 8.23 (s, 1H), 7.92–7.88 (m, 2H), 7.53–7.46 (m, 2H), 6.98 (d, 1H, J=8.0 Hz), 6.56–6.53 (m, 2H), 4.23–4.15 (m, 4H), 3.56 (d, 2H, J=12.5 Hz), 2.43 (s, 3H), 2.16 (s, 3H), 1.52 (s, 9H), 1.35 (t, 6H, J=7.0 Hz). ESI-MS (m/z): Cald. For C29H39N3O7PS3: 668.2 (M+H); found: 667.8.

Workup

  1. customas prepared
  2. temperatureThe mixture was heated at 50° C. for additional 24 h
  3. customSolvent was evaporated
  4. customThe resulting mixture was partitioned between DCM and H2O
  5. customAqueous layer was separated
  6. extractionextracted with DCM
  7. washwashed with H2O and brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated
  10. customflash chromatographed on silica gel column
  11. washeluting with EtOAc/DCM (20 and 30%)

Sources & evidence

ORD record
ord-749529c9e236455a874c96e9e63a1110
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Reaction notes

Loading…