3-(4-Azidophenyl)propionic acid → 3-{4-[4-(1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]phenyl}propanoic acid

HRID 1520011Notes

Reaction equation

HRID 1520011 reaction equation
[N:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][C:12]([OH:14])=[O:13])=[CH:6][CH:5]=1)=[N+:2]=[N-:3].[C:15]([C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[NH:19][N:18]=1)#[CH:16]>O1CCOCC1.O.C(Cl)Cl.CCCCCCC.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2]>[NH:19]1[C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:17]([C:15]2[N:3]=[N:2][N:1]([C:4]3[CH:5]=[CH:6][C:7]([CH2:10][CH2:11][C:12]([OH:14])=[O:13])=[CH:8][CH:9]=3)[CH:16]=2)=[N:18]1

Participants

8

Reactant 2

HCID 135816123-(4-Azidophenyl)propionic acidHCID 178437996HCID 178437996, compound

Product 1

HCID 679812963-{4-[4-(1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]phenyl}propanoic acidYield 75%

Reagents, catalysts & solvents 5

HCID 24463Copper sulfate pentahydrateCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8900HeptaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

3-(4-Azidophenyl)propanoic acid (Bachem, 672 mg; 3.5 mmol; 1.0 eq.) and 3-ethynyl-1H-indazole (500 mg; 3.5 mmol; 1.0 eq.) were dissolved in 1,4-dioxane (7.5 mL). D-(−)-isoascorbic acid sodium salt (139 mg; 0.70 mmol; 0.2 eq.) followed by a solution of copper sulfate pentahydrate (35 mg; 0.14 mmol; 0.04 eq.) in water (0.75 mL) were added. The reaction mixture was stirred at 90° C. for 48 h. Dioxane was partially removed under reduced pressure, water was added and the mixture was extracted with EtOAc (three times). Combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude obtained was sonicated in DCM (5 mL) and heptane (10 mL). The resulting solid was filtered and dried under high vacuum to afford the title compound as a brown solid (875 mg, 75%). 1H NMR (300 Mz, DMSO-d6) δ: 13.37 (brs, 1H), 9.27 (s, 1H), 8.35 (d, J=8.1 Hz, 1H), 7.95 (d, J=8.4 Hz, 2H), 7.61 (d, J=8.4 Hz, 1H), 7.49 (d, J=8.4 Hz, 2H), 7.46-7.41 (m, 1H), 7.27-7.22 (m, 1H), 2.92 (t, J=7.5 Hz, 2H), 2.60 (t, J=7.5 Hz, 2H). HPLC (Condition A): Rt 3.14 min (purity 93.5%). MS (ESI+): 334.2, MS (ESI−): 332.2.

Workup

  1. additionwere added
  2. customDioxane was partially removed under reduced pressure, water
  3. additionwas added
  4. extractionthe mixture was extracted with EtOAc (three times)
  5. washCombined organic layers were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude obtained
  10. filtrationThe resulting solid was filtered
  11. customdried under high vacuum

Sources & evidence

ORD record
ord-add39913defc41c59b66de71a817f120
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

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