Hydrogen Sulfide → 2-[4-(N-(2-[N-(5-chloro-2-pyridyl)carbamoyl]phenyl}carbamoyl)phenyl]benzenecarboxamidine

HRID 842839Notes

Reaction equation

HRID 842839 reaction equation
S.[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[NH:18][C:19]([C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[C:33]#[N:34])=[CH:23][CH:22]=2)=[O:20])=[O:11])=[N:7][CH:8]=1.[NH2:35][C@H](C(O)=O)CCSC>N1C=CC=CC=1.CCN(CC)CC.CC(C)=O.C(O)(=O)C.CO>[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[NH:18][C:19]([C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[C:33]([NH2:35])=[NH:34])=[CH:23][CH:22]=2)=[O:20])=[O:11])=[N:7][CH:8]=1

Participants

9

Reactant 3

HCID 402Hydrogen SulfideHCID 6137L-MethionineHCID 22596431N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]phenyl}[4-(2-cyanophenyl)phenyl)carboxamide

Product 1

HCID 101622622-[4-(N-(2-[N-(5-chloro-2-pyridyl)carbamoyl]phenyl}carbamoyl)phenyl]benzenecarboxamidineYield 15%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolventHCID 180AcetoneSolventHCID 887MethanolSolventHCID 1049PyridineSolventHCID 8471TriethylamineSolvent

Procedure

A stream of H2S (g) was bubbled through a 0° C. solution of N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]phenyl}[4-(2-cyanophenyl)phenyl]carboxamide (100 mg. 0.22 mmol, 1.0 equiv.) in 9 mL pyridine and 1 mL NEt3 until saturation. The mixture was stirred at rt for 1 day and evaporated. The resulting residue was treated with Met (94 mg, 0.663 mmol, 3.0 equiv.) in 10 mL acetone at reflux temperature for 1 hr and concentrated to dryness. The resulting residue was treated with a mixture of NH4OAc (340 mg, 4.42 mmol, 20 equiv.) in 0.5 mL acetic acid and 2 mL methanol at 50° C. for 2 days. The solvent was removed at reduced pressure and the crude benzamidine was purified by HPLC (C18 reversed phase) eluting with 0.1% TFA in H2O/CH3CN to give 2-[4-(N-{2-[N-(5-chloro-2-pyridyl)carbamoyl]phenyl }carbamoyl)phenyl]benzenecarboxamidine (15 mg, 15%). MS found for C26H20ClN5O, (M+H)+: 470.

Workup

  1. customevaporated
  2. temperatureat reflux temperature for 1 hr
  3. concentrationconcentrated to dryness
  4. customThe solvent was removed at reduced pressure
  5. customthe crude benzamidine was purified by HPLC (C18 reversed phase)
  6. washeluting with 0.1% TFA in H2O/CH3CN

Sources & evidence

ORD record
ord-bc960540f3dc469ab06455073cb0b964
Source dataset
uspto-grants-2002_04
Patent number
US06376515B2

Reaction notes

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