Methyl chloroformate → HCID 59355471, compound

HRID 887722Notes

Reaction equation

HRID 887722 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]([N:10]([CH:12]([CH3:14])[CH3:13])[NH2:11])=[O:9])[C:5]([NH:15][C:16]([C:18]2[N:19]([C:24]3[C:29]([Cl:30])=[CH:28][CH:27]=[CH:26][N:25]=3)[N:20]=[C:21]([Br:23])[CH:22]=2)=[O:17])=[C:4]([CH3:31])[CH:3]=1.Cl[C:33]([O:35][CH3:36])=[O:34]>N1C=CC=CC=1>[CH3:36][O:35][C:33]([NH:11][N:10]([C:8]([C:6]1[C:5]([NH:15][C:16]([C:18]2[N:19]([C:24]3[C:29]([Cl:30])=[CH:28][CH:27]=[CH:26][N:25]=3)[N:20]=[C:21]([Br:23])[CH:22]=2)=[O:17])=[C:4]([CH3:31])[CH:3]=[C:2]([Cl:1])[N:7]=1)=[O:9])[CH:12]([CH3:13])[CH3:14])=[O:34]

Participants

4

Reactant 2

HCID 6586Methyl chloroformate2×HCID 59355304HCID 59355304, compound

Product 1

HCID 59355471HCID 59355471, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
50 °C

Procedure

5-Bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carboxylic acid [6-chloro-2-(N-isopropyl-hydrazinocarbonyl)-4-methyl-pyridin-3-yl]-amide (13-a) (121 mg) was dissolved in pyridine (2 mL), methyl chloroformate (70 μL) was added and the reaction mixture was stirred at 50° C. After 1 h, methyl chloroformate (each 40 μL) was added 8× in a time interval of 30 min at 50° C. After 10 h stirring at room temperature, the reaction mixture was quenched with water and 3× co-evaporated with toluene. The residue was dissolved in water and ethyl acetate, the layers were separated and the aqueous layer was extracted 2× with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuum. The residue was purified by column chromatography (silica 60, chloroform/ethyl acetate=3:1, Rf=0.15) to afford 67 mg of the title compound (13) of the present invention of the formula

Workup

  1. stirringAfter 10 h stirring at room temperature
  2. customthe reaction mixture was quenched with water and 3× co-evaporated with toluene
  3. dissolutionThe residue was dissolved in water
  4. customethyl acetate, the layers were separated
  5. extractionthe aqueous layer was extracted 2× with ethyl acetate
  6. washThe combined organic layer was washed with brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated in vacuum
  9. customThe residue was purified by column chromatography (silica 60, chloroform/ethyl acetate=3:1, Rf=0.15)

Sources & evidence

ORD record
ord-38584bf82d2c47eba71c94f0fea51e8b
Source dataset
uspto-grants-2012_08
Patent number
US08247431B2

Reaction notes

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