2-Chloro-6-fluorobenzoyl chloride → 2-Chloro-6-fluoro-N-[6-(1-methyl-piperidin-4-ylcarbonyl)-pyridin-2-yl]-benzamide mono-hydrochloride salt

HRID 1667333Notes

Reaction equation

HRID 1667333 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([CH:10]2[CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][CH2:11]2)=[O:9])[N:3]=1.[Cl:17][C:18]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[C:19]=1[C:20](Cl)=[O:21]>O1CCOCC1>[ClH:17].[Cl:17][C:18]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[C:19]=1[C:20]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([CH:10]2[CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][CH2:11]2)=[O:9])[N:3]=1)=[O:21]

Participants

4

Reactant 2

HCID 27365472-Chloro-6-fluorobenzoyl chlorideHCID 11401723(6-Aminopyridin-2-yl)(1-methylpiperidin-4-yl)methanone

Product 1

HCID 179803622-Chloro-6-fluoro-N-[6-(1-methyl-piperidin-4-ylcarbonyl)-pyridin-2-yl]-benzamide mono-hydrochloride saltYield 94%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Combine 2-amino-6-(1-methylpiperidin-4-ylcarbonyl)pyridine (0.18 g, 0.85 mmol), 2-chloro-6-fluoro-benzoyl chloride (0.318 g, 1.65 mmol), and 1,4-dioxane (10 mL). Stir and heat the mixture at reflux. After 2 hr., cool the reaction mixture to ambient-temperature and concentrate. Load the mixture onto an SCX column (10 g), wash with methanol, and elute with 2M ammonia/methanol. Concentrate the eluent to obtain the free base of the title compound (0.30 g, 94%) as an oil. Dissolve the oil in methanol (5 mL) and treat with ammonium chloride (0.045 g, 0.85 mmol). Concentrate the mixture and dry under vacuum to obtain the title compound. HRMS Obs. m/z 376.1237; Calc. m/z 376.1228. m.p. 155° C. (dec).

Workup

  1. temperatureheat the mixture
  2. temperatureat reflux
  3. temperature, cool the reaction mixture to ambient-temperature and
  4. concentrationconcentrate
  5. washLoad the mixture onto an SCX column (10 g), wash with methanol
  6. washelute with 2M ammonia/methanol
  7. concentrationConcentrate the eluent

Sources & evidence

ORD record
ord-dbda141ba5714491b5f7aee8196849b9
Source dataset
uspto-grants-2011_10
Patent number
US08044207B2

Reaction notes

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