Sulfuric acid magnesium salt (1:1) → HCID 58864221, compound

HRID 2355926Notes

Reaction equation

HRID 2355926 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.[C:11]([O:15][CH2:16][CH3:17])(=[O:14])[CH:12]=O.S([O-])([O-])(=O)=O.[Mg+2].[Cl-].[C:25]([O:29][C:30](=[O:33])[CH2:31][Zn+])([CH3:28])([CH3:27])[CH3:26]>O1CCCC1.C(OCC)(=O)C>[CH2:16]([O:15][C:11](=[O:14])[CH:12]([NH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2)[CH2:31][C:30]([O:29][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:33])[CH3:17]

Participants

7

Reactant 4

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 70211Ethyl oxoacetateHCID 880121H-Indazol-5-amineHCID 178451183HCID 178451183, compound

Product 1

HCID 58864221HCID 58864221, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution/suspension of 5-aminoindazole (1.01 g, 7.6 mmol) in tetrahydrofuran (20 mL) was added ethyl glyoxylate solution (ca. 50% in toluene, 1.7 mL, 1.1 equiv) in one portion followed by magnesium sulfate (4.6 g). The mixture was stirred at room temperature overnight (23 h) and then filtered and concentrated in vacuo. The resulting crude imine intermediate (1.3 g, 6 mmol) was dried by azeotroping with anhydrous benzene and further dried under high vacuum. The residue was then dissolved in tetrahydrofuran (20 mL) and cooled at 0° C. A solution of 2-tert-butoxy-2-oxoethylzinc chloride (0.5 M in ether, 24 mL, 2 equiv) was then slowly added. After stirring at 0° C. for 1 h, the mixture was stored at 4° C. overnight. The mixture was then diluted with ethyl acetate and quenched with half-saturated ammonium chloride solution along with a minimum amount of 0.5 N HCl to dissolve the precipitated solids. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water and saturated sodium bicarbonate solution. The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel, eluting with 10% methanol in methylene chloride, to afford the desired product (1.3 g, 65%) as a tan oil. 1H-NMR (400 MHz, CDCl3) δ 7.89 (1H, s), 7.40-7.27 (1H, m), 6.98-6.77 (2H, m), 4.42-4.35 (1H, m), 4.30-4.12 (3H, m), 2.80 (2H, d, J=4.4 Hz), 1.43 (9H, s), 1.27-1.17 (4H, m). Mass spec.: 356.24 (M+Na)+, 278.23 (M−tBu)+, tR=1.287 min.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated in vacuo
  3. customby azeotroping with anhydrous benzene
  4. customfurther dried under high vacuum
  5. dissolutionThe residue was then dissolved in tetrahydrofuran (20 mL)
  6. temperaturecooled at 0° C
  7. stirringAfter stirring at 0° C. for 1 h
  8. waitthe mixture was stored at 4° C. overnight
  9. customquenched with half-saturated ammonium chloride solution along with a minimum amount of 0.5 N HCl
  10. dissolutionto dissolve the precipitated solids
  11. customThe layers were separated
  12. extractionthe aqueous layer was extracted with ethyl acetate
  13. washThe combined organic layers were washed with water and saturated sodium bicarbonate solution
  14. dry with materialThe organic layer was dried over sodium sulfate
  15. concentrationconcentrated in vacuo
  16. customThe crude product was purified by flash column chromatography on silica gel
  17. washeluting with 10% methanol in methylene chloride

Sources & evidence

ORD record
ord-0895fb5572414e7eb4336bc934136870
Source dataset
uspto-grants-2010_07
Patent number
US07754732B2

Reaction notes

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