Cesium carbonate → 7-(2-Fluorophenyl)-3-iodo-2-(2-methyl-2h-[1,2,4]triazol-3-ylmethoxy)pyrazolo[1,5-d][1,2,4]triazine

HRID 1016428Notes

Reaction equation

HRID 1016428 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:13]2[N:14]=[C:15]([OH:18])[C:16]([I:17])=[C:12]2[CH:11]=[N:10][N:9]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl.Cl[CH2:27][C:28]1[N:29]([CH3:33])[N:30]=[CH:31][N:32]=1>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:13]2[N:14]=[C:15]([O:18][CH2:27][C:28]3[N:29]([CH3:33])[N:30]=[CH:31][N:32]=3)[C:16]([I:17])=[C:12]2[CH:11]=[N:10][N:9]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 222853325-(chloromethyl)-1-methyl-1H-1,2,4-triazole hydrochlorideHCID 178518855HCID 178518855, compound

Product 1

HCID 184069027-(2-Fluorophenyl)-3-iodo-2-(2-methyl-2h-[1,2,4]triazol-3-ylmethoxy)pyrazolo[1,5-d][1,2,4]triazineYield 81.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 7-(2-fluorophenyl)-3-iodopyrazolo[1,5-d][1,2,4]triazin-2-ol (0.4098 g, 1.15 mmol) in anhydrous DMF (16 ml) under nitrogen was added cesium carbonate (1.5009 g, 4.61 mmol), then solid 3-chloromethyl-2-methyl-2H-[1,2,4]triazole hydrochloride (0.2328 g, 1.39 mmol). The mixture was stirred at room temperature for 25 h, then partitioned between water (75 ml) and ethyl acetate (75 ml). The aqueous layer was further extracted with ethyl acetate (2×75 ml), and the combined organic extracts were dried (Na2SO4) and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, 0-5% MeOH/EtOAc) to give 0.4212 g (81%) of the title compound as a white solid: mp=218-219° C. (CH2Cl2-EtOAc); 1H NMR (360 MHz, CDCl3) δ 3.88 (3H, s), 5.52 (2H, s), 7.28 (1H, m), 7.39 (1H, td, J=7.6 and 1.0 Hz), 7.65 (1H, m), 7.76 (1H, m), 7.87 (1H, s), 9.14 (1H;, s); MS (ES+) m/e 452 [MH]+; Anal. Found C, 39.66; H, 2.16; N, 21.34%. C15H11FIN7O requires C, 39.93; H, 2.46; N, 21.73%.

Workup

  1. custompartitioned between water (75 ml) and ethyl acetate (75 ml)
  2. extractionThe aqueous layer was further extracted with ethyl acetate (2×75 ml)
  3. dry with materialthe combined organic extracts were dried (Na2SO4)
  4. customevaporated in vacuo
  5. customThe residue was purified by flash chromatography (silica gel, 0-5% MeOH/EtOAc)

Sources & evidence

ORD record
ord-de5f8f956fe14fef9e3a6467172e92cb
Source dataset
uspto-grants-2002_11
Patent number
US06476030B1

Reaction notes

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