Potassium Iodide → 2-Iodo-8-(4-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridine

HRID 1913100Notes

Reaction equation

HRID 1913100 reaction equation
[I-:1].[K+].N([O-])=O.[Na+].[CH3:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:16]3[N:17]([N:21]=[C:22](N)[N:23]=3)[CH:18]=[CH:19][CH:20]=2)=[CH:11][CH:10]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>O.C(#N)C.C(OCC)(=O)C>[I:1][C:22]1[N:23]=[C:16]2[C:15]([C:12]3[CH:13]=[CH:14][C:9]([O:8][CH3:7])=[CH:10][CH:11]=3)=[CH:20][CH:19]=[CH:18][N:17]2[N:21]=1

Participants

8

Reactant 4

HCID 4875Potassium IodideHCID 6101p-Toluenesulfonic acidHCID 23668193Sodium NitriteHCID 591990058-(4-Methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine

Product 1

HCID 591990962-Iodo-8-(4-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridineYield 65.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of potassium iodide (5.4 g, 32 mmol, 3.9 equiv) and sodium nitrite (1.73 g, 25.1 mmol, 3.00 equiv) in water (10 mL) was added over 5 min to a solution of 8-(4-methoxyphenyl)-[1,2,4]-triazolo[1,5-a]pyridin-2-amine (2.01 g, 8.36 mmol, 1 equiv) and p-toluenesulfonic acid (7.3 g, 38 mmol, 4.6 equiv) in acetonitrile at 24° C. After 19 h, the reaction mixture was diluted with ethyl acetate (250 mL), and the resulting solution was washed sequentially with water (2×120 mL) and saturated aqueous sodium chloride solution (120 mL). The collected organic was dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification by flash column chromatography (20→30% ethyl acetate in heptane) provided product as a light yellow solid (1.92 g, 65% yield). 1H NMR (400 MHz, CDCl3), δ: 8.46 (dd, J=6.8, 1.0 Hz, 1 H), 7.96 (m, 2 H), 7.59 (dd, J=7.4, 1.1 Hz, 1 H), 7.01-7.06 (m, 3 H), 3.86 (s, 3 H).

Workup

  1. washthe resulting solution was washed sequentially with water (2×120 mL) and saturated aqueous sodium chloride solution (120 mL)
  2. dry with materialThe collected organic was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification by flash column chromatography (20→30% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-3369fa3545994e13bf1890be4a6feef4
Source dataset
uspto-grants-2013_12
Patent number
US08609687B2

Reaction notes

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