4-Azidobenzoic acid → 4-[4-(1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]benzoic acid

HRID 1520012Notes

Reaction equation

HRID 1520012 reaction equation
[N:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=[O:9])=[CH:6][CH:5]=1)=[N+:2]=[N-:3].[C:13]([C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][N:16]=1)#[CH:14]>O1CCOCC1.O.CCOC(C)=O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2]>[NH:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:15]([C:13]2[N:3]=[N:2][N:1]([C:4]3[CH:5]=[CH:6][C:7]([C:8]([OH:10])=[O:9])=[CH:11][CH:12]=3)[CH:14]=2)=[N:16]1

Participants

7

Reactant 2

HCID 30341844-Azidobenzoic acidHCID 178437996HCID 178437996, compound

Product 1

HCID 679811434-[4-(1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]benzoic acidYield 106%

Reagents, catalysts & solvents 4

HCID 24463Copper sulfate pentahydrateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

4-azidobenzoic acid (252 mg; 1.55 mmol; 1.1 eq.) and 3-ethynyl-1H-indazole (200 mg; 1.4 mmol; 1.0 eq.) were dissolved in 1,4-dioxane (3 mL). D-(−)-isoascorbic acid sodium salt (28 mg; 0.14 mmol; 0.1 eq.) followed by a solution of copper sulfate pentahydrate (7 mg; 0.03 mmol; 0.02 eq.) in water (0.75 mL) were added and the reaction mixture was stirred at 900 for 48 h. Reaction mixture was diluted with EtOAc and extracted with a NaOH (0.1N). Aqueous phase was filtered, acidified to pH 4-5 by addition of HCl (5N) and the precipitate thus obtained, was filtered, washed with water and dried under reduced pressure at 50° C. to afford the title compound as a white solid (453 mg, 100%). 1H NMR (300 MHz, DMSO-d6) δ 13.53 (s, 1H), 9.57 (s, 1H), 8.49 (d, J=8.1 Hz, 1H), 8.42-8.24 (m, 3H), 8.13-8.03 (m, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.63-7.50 (m, 1H), 7.45-7.29 (m, 2H).

Workup

  1. additionwere added
  2. customReaction mixture
  3. extractionextracted with a NaOH (0.1N)
  4. filtrationAqueous phase was filtered
  5. additionacidified to pH 4-5 by addition of HCl (5N)
  6. customthe precipitate thus obtained
  7. filtrationwas filtered
  8. washwashed with water
  9. customdried under reduced pressure at 50° C.

Sources & evidence

ORD record
ord-083cd02a0c6a431590068d184bc3b012
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

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