Hydrochloric Acid → 5-(5-Chloro-3-fluoropyridin-2-yl)-3,6-dimethyl-3,6-dihydro-[1,3,4]-thiadiazine-2-thione

HRID 650494Notes

Reaction equation

HRID 650494 reaction equation
[OH-].[Na+].[CH3:3][NH:4][NH2:5].Cl[CH:7]([CH3:18])[C:8]([C:10]1[C:15]([F:16])=[CH:14][C:13]([Cl:17])=[CH:12][N:11]=1)=O.Cl.[C:20](=[S:22])=[S:21]>O.CCCCCC.C(OCC)(=O)C.C(O)C>[Cl:17][C:13]1[CH:14]=[C:15]([F:16])[C:10]([C:8]2[CH:7]([CH3:18])[S:21][C:20](=[S:22])[N:4]([CH3:3])[N:5]=2)=[N:11][CH:12]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 6061MethylhydrazineHCID 6348Carbon DisulfideHCID 14798Sodium HydroxideHCID 217121612-Chloro-1-(5-chloro-3-fluoropyridin-2-yl)-propan-1-one

Product 1

HCID 217121555-(5-Chloro-3-fluoropyridin-2-yl)-3,6-dimethyl-3,6-dihydro-[1,3,4]-thiadiazine-2-thione

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

19.1 ml of a 4N sodium hydroxide solution and 3.5 g of methyl hydrazine are introduced into 76 ml of ethanol. At an internal temperature of <5° C., 4.5 ml of carbon disulfide are added dropwise with stirring, and the mixture is then stirred for 30 minutes. 17.0 g of 2-chloro-1-(5-chloro-3-fluoropyridin-2-yl)-propan-1-one (Example P36) are subsequently added in the course of 15 minutes at an internal temperature of <5° C. The temperature is then allowed to rise to 22° C. and the mixture is subsequently stirred for 30 minutes. TLC analysis (silica gel 60 F254; eluant: n-hexane/ethyl acetate, UV) of a worked-up sample shows that starting material is no longer present. 2.5 ml of a concentrated hydrochloric acid solution are then added dropwise to form a yellow precipitate. Stirring is carried out for 1 hour and the mixture is then poured into water and extracted with tert-butyl methyl ether. The combined ethereal phases are washed with water, dried over magnesium sulfate, filtered and concentrated to dryness in vacuo. 20.3 g of the desired title compound are obtained in the form of a solid having a melting point of 107-112° C.

Workup

  1. stirringthe mixture is then stirred for 30 minutes
  2. customare subsequently added in the course of 15 minutes at an internal temperature of <5° C
  3. customto rise to 22° C.
  4. stirringthe mixture is subsequently stirred for 30 minutes
  5. customto form a yellow precipitate
  6. stirringStirring
  7. extractionextracted with tert-butyl methyl ether
  8. washThe combined ethereal phases are washed with water
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated to dryness in vacuo

Sources & evidence

ORD record
ord-32538ca0a4844480afc304440578070d
Source dataset
uspto-grants-2001_08
Patent number
US06274536B1

Reaction notes

Loading…