Potassium Sodium Tartrate → HCID 68999893, compound

HRID 1821371Notes

Reaction equation

HRID 1821371 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=[CH:11][C:12]2[CH:22]=[CH:21][CH:20]=[CH:19][C:13]=2/[C:14](/[NH:17][OH:18])=[N:15]\[H])=[N:2]1.[CH2:23]([CH:25](CC(Cl)=O)[C:26](Cl)=[O:27])[CH3:24].[H-].C([Al+]CC(C)C)C(C)C.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>N1C=CC=CC=1.O>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](/[CH:10]=[CH:11]/[C:12]2[CH:22]=[CH:21][CH:20]=[CH:19][C:13]=2[C:14]2[N:15]=[C:24]([CH2:23][CH2:25][CH2:26][OH:27])[O:18][N:17]=2)=[N:2]1

Participants

7

Reactant 4

HCID 9357Potassium Sodium TartrateHCID 21225700DiisobutylaluminumhydrideHCID 218646082-Ethylbutanedioyl dichlorideHCID 178506493HCID 178506493, compound

Product 1

HCID 68999893HCID 68999893, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Conditions

Temperature
90 °C

Procedure

(E)-2-[2-(1H-indazol-3-yl)vinyl]-N-hydroxybenzamidine (0.08 g, 0.29 mmol) obtained in Step 1 of Example 175 was dissolved in pyridine (5.0 mL) and the solution was added with ethylsuccinyl chloride (47 μL, 0.33 mmol), followed by stirring at 90° C. for 1 hour. The reaction mixture was added with water and extracted with ethyl acetate. After the organic layer was concentrated, the residue was added to acetonitrile (5.0 mL) and stirred at 80° C. for 3.5 hours. The reaction mixture was added with water and extracted with ethyl acetate. After the organic layer was concentrated, the residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1 to 1/2) and the residue was dried. Further, the residue was dissolved in a mixed solvent of methylene chloride (1.0 mL)/THF (1.0 mL), cooled to −78° C. and diisobutylaluminum hydride (1.0 mol/L toluene solution, 1.0 mL, 1.0 mmol) was added, followed by stirring for 30 minutes. The reaction mixture was added with saturated aqueous Rochelle salt solution, extracted with ethyl acetate. The organic layer was concentrated, and the residue was purified by preparative thin-layer chromatography (chloroform/methanol=2/1) to obtain Compound 180 (18 mg, 24%).

Workup

  1. extractionextracted with ethyl acetate
  2. concentrationAfter the organic layer was concentrated
  3. additionthe residue was added to acetonitrile (5.0 mL)
  4. stirringstirred at 80° C. for 3.5 hours
  5. additionThe reaction mixture was added with water
  6. extractionextracted with ethyl acetate
  7. concentrationAfter the organic layer was concentrated
  8. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1 to 1/2)
  9. customthe residue was dried
  10. dissolutionFurther, the residue was dissolved in a mixed solvent of methylene chloride (1.0 mL)/THF (1.0 mL)
  11. temperaturecooled to −78° C.
  12. stirringby stirring for 30 minutes
  13. extractionextracted with ethyl acetate
  14. concentrationThe organic layer was concentrated
  15. customthe residue was purified by preparative thin-layer chromatography (chloroform/methanol=2/1)

Sources & evidence

ORD record
ord-582fe6ee69554018989fa70cc443f026
Source dataset
uspto-grants-2009_10
Patent number
US07605272B2

Reaction notes

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