4-Chloropyridine hydrochloride → HCID 19360248, compound

HRID 376883Notes

Reaction equation

HRID 376883 reaction equation
[Cl:1][C:2]1[C:7]2[S:8][CH:9]=[C:10]([NH2:11])[C:6]=2[CH:5]=[CH:4][CH:3]=1.Cl.Cl[C:14]1[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=1>CN1C(=O)CCC1.C([O-])(O)=O.[Na+]>[ClH:1].[Cl:1][C:2]1[C:7]2[S:8][CH:9]=[C:10]([NH:11][C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 818524-Chloropyridine hydrochlorideHCID 193601867-Chlorobenzo[b]thiophen-3-amine

Product 1

HCID 19360248HCID 19360248, compoundYield 59.9%

Reagents, catalysts & solvents 2

HCID 13387N-methyl-2-pyrrolidoneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 7-chloro-3-aminobenzo[b]thiophene (47.82 g, 325 mmole) in NMP (300 mL) was added 4-chloropyridine hydrochloride (50.78 g) and the reaction mixture was placed in a 130° C. oil bath. After stirring for 5 minutes, the reaction mixture was cooled, diluted with a saturated solution of NaHCO3, and extracted with ethyl acetate. The biphasic mixture was thick with precipitates which were removed by filtration over Celite. The organic layer was separated, washed with water, dried (MgSO4), and concentrated. Trituration of the resulting solid with diethyl ether/pentane yielded 28.95 g of product as a green solid. TLC revealed that the precipitates filtered in the initial extraction contained product. Flash chromatography (silica gel) and trituration of the resulting solid with diethyl ether/pentane yielded 11.32 g of an off-white solid. A 2.0 g portion of this material was dissolved in 40 mL of hot methanol allowed to stand for a half hour, filtered to remove orange precipitates. Ethereal hydrogen chloride was added to the filtrate. The hydrochloride salt was then filtered, washed with diethyl ether, and dried under high vacuum, P2O5, and refluxing xylenes to yield 1.89 g of a beige crystalline solid, mp 305° C. (dec.).

Workup

  1. customwas placed in a 130° C.
  2. temperaturethe reaction mixture was cooled
  3. extractionextracted with ethyl acetate
  4. customwith precipitates which
  5. customwere removed by filtration over Celite
  6. customThe organic layer was separated
  7. washwashed with water
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-effb1ce38a564c5f91cc50bca8b47546
Source dataset
uspto-grants-2000_02
Patent number
US06022880

Reaction notes

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