Potassium Sodium Tartrate → HCID 68999673, compound

HRID 1821372Notes

Reaction equation

HRID 1821372 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.C(N(C(C)C)CC)(C)C.[CH2:32]([CH:34](C(Cl)=O)[C:35](Cl)=[O:36])C.C(=O)([O-])[O-].[K+].[K+].[H-].C([Al+]CC(C)C)C(C)C.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C1COCC1.O.CO>[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:32]([CH2:34][CH2:35][OH:36])[O:18][N:17]=2)=[N:2]1

Participants

10

Reactant 6

HCID 9357Potassium Sodium TartrateHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 109209242-Ethylpropanedioyl dichlorideHCID 21225700DiisobutylaluminumhydrideHCID 178506493HCID 178506493, compound

Product 1

HCID 68999673HCID 68999673, compoundYield 45.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °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 THF (5.0 mL) and the solution was added with diisopropylethylamine (0.12 mL, 0.66 mmol) and ethylmalonyl chloride (47 μL, 0.44 mmol), followed by stirring at 80° C. for 15 minutes. Then, potassium carbonate and methanol were added to the mixture and stirred for 30 minutes. The mixture was added with water, extracted with ethyl acetate, and the organic layer was concentrated and then dried. Further, the residue was dissolved in a mixed solvent of methylene chloride (1.0 mL) and THF (1.0 mL), cooled to −78° C. and diisobutylaluminum hydride (0.95 mol/L toluene solution, 0.58 mL, 0.55 mmol) was added. The mixture was warmed to room temperature and stirred for 3 hours. The reaction mixture was added with saturated aqueous Rochelle salt solution and extracted with ethyl acetate. After the organic layer was concentrated, the residue was triturated in ethyl acetate to obtain Compound 181 (44 mg, 35%).

Workup

  1. stirringstirred for 30 minutes
  2. extractionextracted with ethyl acetate
  3. concentrationthe organic layer was concentrated
  4. customdried
  5. dissolutionFurther, the residue was dissolved in a mixed solvent of methylene chloride (1.0 mL) and THF (1.0 mL)
  6. temperaturecooled to −78° C.
  7. temperatureThe mixture was warmed to room temperature
  8. stirringstirred for 3 hours
  9. extractionextracted with ethyl acetate
  10. concentrationAfter the organic layer was concentrated
  11. customthe residue was triturated in ethyl acetate

Sources & evidence

ORD record
ord-d42069cc580a498b85208ca67ca3c983
Source dataset
uspto-grants-2009_10
Patent number
US07605272B2

Reaction notes

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