Dimethylamine → (E)-N,N-Dimethyl-4-[2-(1H-indazol-3-yl)vinyl]benzamide

HRID 2075432Notes

Reaction equation

HRID 2075432 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:20]=[CH:19][C:15]([C:16](O)=[O:17])=[CH:14][CH:13]=2)=[N:2]1.[CH3:21][NH:22][CH3:23].ON1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C>C1COCC1>[CH3:21][N:22]([CH3:23])[C:16](=[O:17])[C:15]1[CH:19]=[CH:20][C:12](/[CH:11]=[CH:10]/[C:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[NH:1][N:2]=2)=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 674DimethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 11437002(E)-4-(2-(1H-indazol-3-yl)vinyl)benzoic acid

Product 1

HCID 11300788(E)-N,N-Dimethyl-4-[2-(1H-indazol-3-yl)vinyl]benzamideYield 3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Procedure

A mixture of a solution of (E)-4-[2-(1H-indazol-3-yl)vinyl]benzoic acid obtained in Step 6 in THF (0.125 mol/L, 0.40 mL, 0.05 mmol), a solution of dimethylamine in THF (1 mol/L, 0.08 mL, 0.08 mmol), a solution of 1-hydroxybenzotriazole in THF (0.33 mol/L, 0.20 mL, 0.07 mmol) and polymer-bound 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (1 mol/g, 0.07 g, 0.07 mmol) was shaken at room temperature overnight. The reaction mixture was filtered, the solvent was evaporated by blowing air to the filtrate, and the residue was added with THF (0.6 mL), polyvinylpyridine (0.03 g, 0.29 mmol) and 4-chloroformyl polystyrene (3.5 mol/g, 0.03 g, 0.11 mmol), followed by shaking at room temperature overnight. The reaction mixture was filtered, and the solvent was evaporated by blowing air to the filtrate. The residue was added with ethanol (0.5 mL) and ion-exchange resin [Bio-Rad AG (registered trademark) 1 X-8 OH form, 0.15 g], followed by shaking for 10 minutes. The mixture was filtered, the resin was washed with ethanol, and the adsorbate was eluted with a 4 mol/L solution of hydrogen chloride in ethyl acetate. The solvent was evaporated by blowing air to the eluate, the residue was purified by thin-layer chromatography (chloroform/methanol=9/1) to obtain Compound 1 (0.4 mg, 3%).

Workup

  1. filtrationThe reaction mixture was filtered
  2. customthe solvent was evaporated
  3. filtrationThe reaction mixture was filtered
  4. customthe solvent was evaporated
  5. additionThe residue was added with ethanol (0.5 mL) and ion-exchange resin [Bio-Rad AG (registered trademark) 1 X-8 OH form, 0.15 g]
  6. stirringby shaking for 10 minutes
  7. filtrationThe mixture was filtered
  8. washthe resin was washed with ethanol
  9. washthe adsorbate was eluted with a 4 mol/L solution of hydrogen chloride in ethyl acetate
  10. customThe solvent was evaporated
  11. customthe residue was purified by thin-layer chromatography (chloroform/methanol=9/1)

Sources & evidence

ORD record
ord-10cb9a9d72ca4b93b26bff5c0e2a77fe
Source dataset
uspto-grants-2011_04
Patent number
US07919517B2

Reaction notes

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