Toluene → 4-Chloro-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl 2,2-dimethylpropanoate

HRID 1393935Notes

Reaction equation

HRID 1393935 reaction equation
[C:1]([O:7][C:8]1[C:9]([CH3:18])=[C:10]2[N:15]([CH:16]=1)[N:14]=[CH:13][NH:12][C:11]2=O)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].P(Cl)(Cl)([Cl:21])=O.CCN(C(C)C)C(C)C.C1(C)C=CC=CC=1>C(OCC)(=O)C.O>[C:1]([O:7][C:8]1[C:9]([CH3:18])=[C:10]2[N:15]([CH:16]=1)[N:14]=[CH:13][N:12]=[C:11]2[Cl:21])(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]

Participants

7

Reactant 4

HCID 1140TolueneHCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 1356205694-Hydroxy-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl 2,2-dimethylpropanoate

Product 1

HCID 210816794-Chloro-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl 2,2-dimethylpropanoateYield 78%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of 5-methyl-4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-6-yl pivalate (300 mg, 1.20 mmol), phosphorus oxychloride (2.0 mL, 21.4 mmol) and DIEA (0.5 mL, 2.80 mmol) was added toluene (10 mL). The reaction was heated at 110° C. for 4 hours and then cooled to room temperature. The mixture was diluted with ethyl acetate (10 mL) and water (5 mL). The organic layer was separated and dried with sodium sulfate, concentrated in vacuo and purified by silica gel flash chromatography (eluted with 1-25% EtOAc/CH2Cl2) to give the title compound (250 mg, 78%) as a white solid.

Workup

  1. temperaturecooled to room temperature
  2. customThe organic layer was separated
  3. dry with materialdried with sodium sulfate
  4. concentrationconcentrated in vacuo
  5. custompurified by silica gel flash chromatography (eluted with 1-25% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-ddd1852d3c324accab385a4eb298b8e9
Source dataset
uspto-grants-2008_03
Patent number
US07348325B2

Reaction notes

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