HCID 568239, compound → HCID 10270181, compound

HRID 2183437Notes

Reaction equation

HRID 2183437 reaction equation
[NH2:1][C:2]1[S:3][CH2:4][CH:5]([CH3:7])[N:6]=1.Br[CH2:9][C:10]1[CH:11]=[CH:12][C:13]([Cl:16])=[N:14][CH:15]=1>C(#N)C>[Cl:16][C:13]1[N:14]=[CH:15][C:10]([CH2:9][N:6]2[C:5]([CH3:7])=[CH:4][S:3][C:2]2=[N:1][CH2:9][C:10]2[CH:15]=[N:14][C:13]([Cl:16])=[CH:12][CH:11]=2)=[CH:11][CH:12]=1

Participants

4

Reactant 2

HCID 568239HCID 568239, compoundHCID 64246615-(Bromomethyl)-2-chloropyridine

Product 1

HCID 10270181HCID 10270181, compoundYield 42.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 228 mg (2 mmol) of 2-amino-4-methylthiazoline and 1.03 g (5 mmol) of 5-bromomethyl-2-chloropyridine in 30 ml of acetonitrile was heated for 8 hours at 90° C. under refluxing. Then, the reaction mixture was cooled to the room temperature, and the solvent was removed under reduced pressure. The resulting residue was mixed with dichloromethane and saturated sodium hydrogen carbonate aqueous solution, and the organic layer was separated. The water layer was extracted with dichloromethane, and combined organic layer was dried over magnesium sulfate. The solvent was removed under reduced pressure and the resulting residue was purified by silica gel 60 (Merck Co., Ltd.) column chromatography (eluent; dichloromethane:ethyl acetate=from 9:1 to 4:1) to give 600 mg (yield; 82.1%) of crude product as yellow oil. Then, this crude product was purified again by aminopropyl-coated silica gel (Chromatorex NH-type; Fuji Silysia Chemical Ltd.) column chromatography (eluent; dichloromethane), and the eluted product was crystallized by treatment with ether-isopropyl ether to give 310 mg (yield; 42.4%) of 3-(6-chloro-3-pyridyl)methyl-2-[(6-chloro-3-pyridyl)methyl]imino-4-methyl-2,3-dihydrothiazole as milky white crystalline. 200 mg (0.548 mmol) of this product was dissolved in methanol and to this solution was added 64 mg (0.551 mmol) of fumaric acid, and the mixture was concentrated under reduced pressure. The resulting residue was treated with acetonitrile to give crystalline. The crystalline was collected by filtration and dried in vacuum to give 213 mg of fumarate of the title Compound 9.

Workup

  1. temperatureunder refluxing
  2. temperatureThen, the reaction mixture was cooled to the room temperature
  3. customthe solvent was removed under reduced pressure
  4. additionThe resulting residue was mixed with dichloromethane and saturated sodium hydrogen carbonate aqueous solution
  5. customthe organic layer was separated
  6. extractionThe water layer was extracted with dichloromethane
  7. dry with materialwas dried over magnesium sulfate
  8. customThe solvent was removed under reduced pressure
  9. customthe resulting residue was purified by silica gel 60 (Merck Co., Ltd.) column chromatography (eluent; dichloromethane:ethyl acetate=from 9:1 to 4:1)
  10. customto give 600 mg (yield; 82.1%) of crude product as yellow oil
  11. customThen, this crude product was purified again by aminopropyl-coated silica gel (Chromatorex NH-type; Fuji Silysia Chemical Ltd.) column chromatography (eluent; dichloromethane)
  12. customthe eluted product was crystallized by treatment with ether-isopropyl ether

Sources & evidence

ORD record
ord-ac9344bd732b456098f45db06178eaa0
Source dataset
uspto-grants-2005_05
Patent number
US06900202B2

Reaction notes

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