3-Bromothiophene-2-carbonyl chloride → 3-Bromo-N-[6-(1-methyl-piperidin-4-ylcarbonyl)-pyridin-2-yl]-thiophene-2-carboxamide mono-hydrochloride salt

HRID 404231Notes

Reaction equation

HRID 404231 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.[Br:17][C:18]1[CH:22]=[CH:21][S:20][C:19]=1[C:23]([Cl:25])=[O:24]>O1CCOCC1>[ClH:25].[Br:17][C:18]1[CH:22]=[CH:21][S:20][C:19]=1[C:23]([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:24]

Participants

4

Reactant 2

HCID 27975693-Bromothiophene-2-carbonyl chlorideHCID 11401723(6-Aminopyridin-2-yl)(1-methylpiperidin-4-yl)methanone

Product 1

HCID 179803843-Bromo-N-[6-(1-methyl-piperidin-4-ylcarbonyl)-pyridin-2-yl]-thiophene-2-carboxamide mono-hydrochloride saltYield 78%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Combine 2-amino-6-(1-methylpiperidin-4-ylcarbonyl)pyridine (0.104 g, 0.48 mmol), 3-Bromo-thiophene-2-carbonyl chloride (0.215 g, 0.95 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 as an oil (0.152 g, 78%). Dissolve the oil in dichloromethane (10 mL), treat with 1M hydrogen chloride in ether, concentrate and dry under vacuum to obtain the title compound. HRMS Obs. m/z 408.0384, Calc. m/z 408.0381; m.p. 195-200° C.

Workup

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

Sources & evidence

ORD record
ord-1ac7f85db05e4b61b6f3ae45f0b547c0
Source dataset
uspto-grants-2014_06
Patent number
US08748459B2

Reaction notes

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