Dichloromethane → HCID 11612963, compound

HRID 1716613Notes

Reaction equation

HRID 1716613 reaction equation
[C:1]([C:3]1[C:7]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])=[C:6]([N:13]=CN(C)C)[N:5]([C:18]2[C:23]([Cl:24])=[CH:22][C:21]([C:25]([F:28])([F:27])[F:26])=[CH:20][C:19]=2[Cl:29])[N:4]=1)#[N:2].[H-].[Na+].ClC(Cl)(Cl)S(O[CH2:38][C:39]([F:42])([F:41])[F:40])(=O)=O.ClCCl>CN1CCCC1=O>[NH2:13][C:6]1[N:5]([C:18]2[C:19]([Cl:29])=[CH:20][C:21]([C:25]([F:26])([F:27])[F:28])=[CH:22][C:23]=2[Cl:24])[N:4]=[C:3]([C:1]#[N:2])[C:7]=1[N:8]([CH2:38][C:39]([F:42])([F:41])[F:40])[S:9]([CH3:12])(=[O:10])=[O:11]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 24758Sodium hydrideHCID 900272,2,2-Trifluoroethyl trichloromethanesulphonateHCID 68517863HCID 68517863, compound

Product 1

HCID 11612963HCID 11612963, compoundYield 51.3%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of N-(3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-{[(dimethylamino)methylene]amino}-1H-pyrazol-4-yl)methanesulfonamide (250 mg, 0.53 mmol) in 1-methyl-2-pyrrolidinone (anhydrous, 5 ml) was added sodium hydride (60% in oil, 16.6 mg, 0.69 mmol) and 2,2,2-trifluoroethyl trichloromethanesulphonate (195 mg, 0.69 mmol). The reaction mixture was then stirred at room temperature for 3 h. To the reaction mixture was added dichloromethane (20 ml) and the resulting mixture was extracted with water (20 ml). The organic phase was washed with water (2×20 ml) and brine (2×20 ml), dried (Na2SO4) and concentrated in vacuo. To the residue was added methanol (5 ml) and hydrochloric acid (4M, 3 ml) and the mixture was heated at reflux for 60 h. The reaction mixture was concentrated in vacuo and to the residue was added ethyl acetate (20 ml) and water (20 ml). The organic phase was separated, washed with water (2×20 ml) and brine (2×20 ml), dried (Na2SO4) and concentrated in vacuo. The crude product was dissolved in acetonitrile/dimethyl sulphoxide/water (1:4:1, 6 ml) and purified by automated preparative liquid chromatography (Gilson system, 150 mm×30 mm Phenomonex LUNA C18(2) 10 μm column) using an acetonitrile:water gradient [52.5:47.5 to 95:5]. The appropriate fractions were concentrated in vacuo to give the titled compound (135 mg).

Workup

  1. extractionthe resulting mixture was extracted with water (20 ml)
  2. washThe organic phase was washed with water (2×20 ml) and brine (2×20 ml)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. additionTo the residue was added methanol (5 ml) and hydrochloric acid (4M, 3 ml)
  6. temperaturethe mixture was heated
  7. temperatureat reflux for 60 h
  8. concentrationThe reaction mixture was concentrated in vacuo and to the residue
  9. additionwas added ethyl acetate (20 ml) and water (20 ml)
  10. customThe organic phase was separated
  11. washwashed with water (2×20 ml) and brine (2×20 ml)
  12. dry with materialdried (Na2SO4)
  13. concentrationconcentrated in vacuo
  14. dissolutionThe crude product was dissolved in acetonitrile/dimethyl sulphoxide/water (1:4:1, 6 ml)
  15. custompurified
  16. concentrationThe appropriate fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-35405e87b28d456081b1fca48f0965ee
Source dataset
uspto-grants-2010_09
Patent number
US07803832B2

Reaction notes

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