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

HRID 2114009Notes

Reaction equation

HRID 2114009 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.C(#N)C>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 6342AcetonitrileHCID 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
87.5 °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 (368 mg mL, 2.4 mmol) and DIEA (0.5 mL, 2.80 mmol) was added acetonitrile (10 mL). The reaction was heated at 85-90° 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-69f6ca967aa24c92b39a8649ecba0d7b
Source dataset
uspto-grants-2008_10
Patent number
US07432373B2

Reaction notes

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