Quinone → HCID 178511944, compound

HRID 1622154Notes

Reaction equation

HRID 1622154 reaction equation
C[O:2][C:3](=[O:36])[CH2:4][C:5]1[CH:6]=[C:7]([C:20]2[CH:25]=[C:24]([S:26](=[O:33])(=[O:32])[NH:27]C(C)(C)C)[CH:23]=[CH:22][C:21]=2[O:34]C)[C:8]([O:13]COCCOC)=[C:9]([CH:11]=O)[CH:10]=1.Cl.[NH2:38][C:39]1[CH:40]=[C:41]([CH:45]=[CH:46][C:47]=1[NH2:48])[C:42]([NH2:44])=[NH:43].C1(=O)C=CC(=O)C=C1.Cl.N1C=CC=CC=1>CO>[C:42]([C:41]1[CH:45]=[CH:46][C:47]2[NH:48][C:11]([C:9]3[CH:10]=[C:5]([CH2:4][C:3]([OH:2])=[O:36])[CH:6]=[C:7]([C:20]4[CH:25]=[C:24]([S:26](=[O:32])(=[O:33])[NH2:27])[CH:23]=[CH:22][C:21]=4[OH:34])[C:8]=3[OH:13])=[N:38][C:39]=2[CH:40]=1)(=[NH:43])[NH2:44]

Participants

6

Reactant 4

HCID 4650QuinoneHCID 10176127Pyridinium chlorideHCID 221255323,4-Diaminobenzimidamide hydrochlorideHCID 86628079Methyl [5'-tert-butylsulfamoyl-5-formyl-2'-methoxy-6-(2-methoxyethoxymethoxy)biphenyl-3-yl]acetate

Product 1

HCID 178511944HCID 178511944, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
180 °C

Procedure

Methyl[5′-tert-butylsulfamoyl-5-formyl-2′-methoxy-6-(2-methoxyethoxymethoxy)biphenyl-3-yl]acetate (0.496 g, 1.1 mmol), prepared as in Reference 8, was dissolved in methanol (20 mL) and the solution was charged with 3,4-diaminobenzamidine-HCl (1.25 mmol, 0.23 g) and 1,4-benzoquinone (1.25 mmol, 0.135 g). The mixture was refluxed for 2 hours and then concentrated by evaporation. This residue was taken up in trifluoroacetic acid (10 mL) and the mixture was stirred for 1 hour. Evaporation and further pumping down yielded a purple amorphous residue. Pyridine hydrochloride (5.0 g) was added and the reaction mixture was heated at 180° C. for 30 minutes. The mixture was cooled and a resulting solid was dissolved in 20 mL of preparative hplc sample solvent (20% acetonitrile/20 mmol HCl). The product was purified by preparative hplc (C-18, 2,2,25 acetonitrile). The fractions containing the pure product were collected and lyophilized to give [5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoylbiphenyl-3-yl]acetic acid (0.31 g, 59%). LCMS: Calcd 481.49; Obsd (MH+)=482.0, (MH−)=480.2. NMR (DMSO-d6) d 3.621 (s, 2H), 7.07 (d, J=8 Hz, 1H), 7.15 (br s, 2H), 7.27 (d, J=2 Hz, 1H), 7.63 (d, J=2 Hz, 1H), 7.65 (m, 2H), 7.73 (d of d, J=2, J=8 Hz, 1H), 7.83 (d, J=8 Hz, 1H), 8.08 (d, J=2 Hz, 1H), 8.17 (s, 1H), 9.10, 9.39 (2s, 4H).

Workup

  1. temperatureThe mixture was refluxed for 2 hours
  2. concentrationconcentrated by evaporation
  3. customEvaporation
  4. customfurther pumping down yielded a purple amorphous residue
  5. temperatureThe mixture was cooled
  6. customThe product was purified by preparative hplc (C-18, 2,2,25 acetonitrile)
  7. additionThe fractions containing the pure product
  8. customwere collected

Sources & evidence

ORD record
ord-4399f7f9a41747d591f68ba297fc9c97
Source dataset
uspto-grants-2014_07
Patent number
US08778625B2

Reaction notes

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