Hydrochloric Acid → 3-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propan-1-ol

HRID 1459708Notes

Reaction equation

HRID 1459708 reaction equation
[CH:1]1[C:6]([NH:7]N)=[CH:5][CH:4]=[C:3]([N:9]2[CH:13]=[N:12][N:11]=[CH:10]2)[CH:2]=1.[O:14]1[CH:19]=[CH:18][CH2:17][CH2:16][CH2:15]1.Cl>O1CCOCC1>[N:12]1[N:11]=[CH:10][N:9]([C:3]2[CH:2]=[C:1]3[C:6](=[CH:5][CH:4]=2)[NH:7][CH:19]=[C:18]3[CH2:17][CH2:16][CH2:15][OH:14])[CH:13]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 80803,4-dihydro-2H-pyranHCID 51624184-(4-hydrazinylphenyl)-4H-1,2,4-triazole

Product 1

HCID 106339143-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propan-1-olYield 30%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 4'-(1,2,4-triazol-4-yl)phenylhydrazine (25 g, 143 mmol) in dioxan (250 ml) was treated with dihydropyran (24 g, 286 mmol) followed by 1M hydrochloric acid (150 ml) and heated at reflux for 18 h. The reaction mixture was evaporated, treated with toluene then re-evaporated. Inorganic solids were removed by treating the residue with a mixture of methanol and acetonitrile. The mother liquors were purified by column chromatography on silica using dichloromethane/methanol (9:1→4:1) as the eluant. The compound was recrystallised from acetonitrile to afford the title compound as a colourless solid (10.24 g, 30%); mp 205°-207° C. (Found: C, 64.37; H, 5.76; N, 22.83. C13H14N4O requires C, 64.45; H, 5.82; N, 23.13%.) δ (360 MHz, d6 -DMSO) 1.81 (2H, q, J=7 Hz, CH2), 2.75 (2H, t, J=8 Hz, CH2), 3.46 (2H, dt, J1 =6, J2 =5 Hz, CH2), 4.43 (1H, t, J=5 Hz, OH), 7.26 (1H, d, J=2 Hz, Ar--H), 7.29 (1H, dd, J1 =9, J2 =2 Hz, Ar--H), 7.47 (1H, d, J=9 Hz, Ar--H), 7.77 (1H, d, J=2 Hz, Ar--H), 9.01 (2H, s, triazole-H), 11.05 (1H, br s, indole NH). MS, CI+, m/z=243 for (M+H)+.

Workup

  1. temperatureheated
  2. temperatureat reflux for 18 h
  3. customThe reaction mixture was evaporated
  4. additiontreated with toluene
  5. customthen re-evaporated
  6. customInorganic solids were removed
  7. additionby treating the residue
  8. additionwith a mixture of methanol and acetonitrile
  9. customThe mother liquors were purified by column chromatography on silica
  10. customThe compound was recrystallised from acetonitrile

Sources & evidence

ORD record
ord-5444e45af06b4fb4a9a8f9bd6a917b03
Source dataset
uspto-grants-1998_12
Patent number
US05854268

Reaction notes

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