Hydrochloric Acid → HCID 24946635, compound

HRID 1891305Notes

Reaction equation

HRID 1891305 reaction equation
C([O-])([O-])=O.[K+].[K+].[I-].[K+].[CH2:9](Br)[CH3:10].[F:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][NH:21][CH2:22][CH:23]2[CH2:28][CH2:27][N:26]([C:29]([C:31]3[N:32]([CH3:40])[N:33]=[C:34]4[C:39]=3[CH:38]=[CH:37][CH:36]=[CH:35]4)=[O:30])[CH2:25][CH2:24]2)=[CH:15][CH:14]=1.[ClH:41]>C(O)C>[ClH:41].[CH2:9]([N:21]([CH2:22][CH:23]1[CH2:28][CH2:27][N:26]([C:29]([C:31]2[N:32]([CH3:40])[N:33]=[C:34]3[C:39]=2[CH:38]=[CH:37][CH:36]=[CH:35]3)=[O:30])[CH2:25][CH2:24]1)[CH2:20][CH2:19][C:16]1[CH:17]=[CH:18][C:13]([F:12])=[CH:14][CH:15]=1)[CH3:10]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 6332Ethyl BromideHCID 11430Potassium CarbonateHCID 24946639HCID 24946639, compound

Product 1

HCID 24946635HCID 24946635, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Procedure

K2CO3 (0.71 g; 0.0052 mol), potassium iodide (10 mg; 0.062 mmol) and ethyl bromide (0.54 ml; 0.0072 mol) were added to a solution of 2-(4-fluorophenyl)-N-({1-[(2-methyl-2H-indazol-3-yl)carbonyl]piperidin-4-yl}methyl)ethanamine (10a) (1.7 g; 0.0043 mol) in absolute ethanol (20 ml). The mixture was heated under reflux for 48 h and then the solvent was evaporated at reduced pressure. The residue was taken up in chloroform and was washed with water twice. The organic phase was dried over Na2SO4, filtered and concentrated at reduced pressure. The resultant raw compound (1.5 g) was purified by flash chromatography (ethyl acetate/n-hexane/ammonia=96/4/0.2). The compound obtained (0.5 g) was converted to its hydrochloride by dissolving in absolute ethanol and treatment with an excess of 5N hydrochloric ethanol for 3 h. After evaporation of the solvent at reduced pressure, the solid residue was crystallized from ethanol/ethyl acetate, obtaining 0.15 g of N-ethyl-2-(4-fluorophenyl)-N-({1-[(2-methyl-2H-indazol-3-yl)carbonyl]piperidin-4-yl}methyl)ethanamine hydrochloride.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 48 h
  3. customthe solvent was evaporated at reduced pressure
  4. washwas washed with water twice
  5. dry with materialThe organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated at reduced pressure
  8. customThe resultant raw compound (1.5 g) was purified by flash chromatography (ethyl acetate/n-hexane/ammonia=96/4/0.2)
  9. customThe compound obtained (0.5 g)
  10. customAfter evaporation of the solvent at reduced pressure
  11. customthe solid residue was crystallized from ethanol/ethyl acetate

Sources & evidence

ORD record
ord-c86bf46f7c2b4626b4c6de39baa5a25e
Source dataset
uspto-grants-2013_08
Patent number
US08507528B2

Reaction notes

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