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

HRID 1602094Notes

Reaction equation

HRID 1602094 reaction equation
[N:1]1[N:2]=[CH:3][N:4]([C:6]2[CH:11]=[CH:10][C:9]([NH:12]N)=[CH:8][CH:7]=2)[CH:5]=1.[O:14]1[CH:19]=[CH:18][CH2:17][CH2:16][CH2:15]1.Cl>O1CCOCC1>[N:1]1[N:2]=[CH:3][N:4]([C:6]2[CH:11]=[C:10]3[C:9](=[CH:8][CH:7]=2)[NH:12][CH:19]=[C:18]3[CH2:17][CH2:16][CH2:15][OH:14])[CH:5]=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 hours. The reaction mixture was evaporated with toluene then reevaporated. 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 white solid (10.24 g, 30%), mp 205-207° C. δ(360 MHz, d6 -DMSO) 1.81 (2H, quintet, J=7 Hz, CH2), 2.75 (2H, t, J=8 Hz, CH2), 3.46 (2H, dt, J1 =6 Hz, 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 Hz, 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 for (M+H)+ =243.

Workup

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

Sources & evidence

ORD record
ord-59183bc0c76d4ba2865847d90fda823f
Source dataset
uspto-grants-1999_11
Patent number
US05981529

Reaction notes

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