Potassium Carbonate → HCID 53482797, compound

HRID 2272925Notes

Reaction equation

HRID 2272925 reaction equation
[ClH:1].[NH:2]1[CH2:7][CH2:6][CH:5]([CH2:8][N:9]2[CH2:21][CH2:20][N:12]3[N:13]=[C:14]4[C:19]([CH:18]=[CH:17][CH:16]=[CH:15]4)=[C:11]3[C:10]2=[O:22])[CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].[F:29][C:30]1[CH:38]=[CH:37][C:33]([CH2:34][CH2:35]Br)=[CH:32][CH:31]=1>C(O)C>[ClH:1].[F:29][C:30]1[CH:38]=[CH:37][C:33]([CH2:34][CH2:35][N:2]2[CH2:7][CH2:6][CH:5]([CH2:8][N:9]3[CH2:21][CH2:20][N:12]4[N:13]=[C:14]5[C:19]([CH:18]=[CH:17][CH:16]=[CH:15]5)=[C:11]4[C:10]3=[O:22])[CH2:4][CH2:3]2)=[CH:32][CH:31]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 5731534-Fluorophenethyl bromideHCID 71224372HCID 71224372, compound

Product 1

HCID 53482797HCID 53482797, compoundYield 34.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution containing 2-(piperidin-4-yl-methyl)-3,4-dihydropyrazino[1,2-b]indazol-1(2H)-one hydrochloride (528 mg; 1.64 mmol), potassium carbonate (610 mg; 4.4 mmol), 4-fluorophenethyl bromide (450 mg; 2.2 mmol) in ethanol (10 ml) was kept stirred under reflux for 24 h. The reaction was then stopped by cooling the mixture at room temperature and concentrating the solvent under reduced pressure. The residue was taken up with DCM (30 ml) and washed respectively with a saturated solution of NaHCO3 (2×20 ml), water (2×15 ml) and a saturated solution of NaCl (10 ml). The organic phase was then dried with Na2SO4 and the solvent was removed by evaporation at reduced pressure. The solid raw product was then purified by flash chromatography on silica gel, using as eluent a mixture of chloroform:methanol in a ratio of 9:1. The product thus purified was dissolved in a mixture of diethyl ether:ethanol in a ratio of 10:1 (10 ml) and treated at room temperature with 3M hydrochloric ethanol (0.33 ml). The solid thus formed was filtered and crystallized by a mixture isopropanol:diisopropyl ether in a ratio of 3:7. Thus, 250 mg of 2-({1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl}methyl)-3,4-dihydropyrazino[1,2-b]-indazol-1(2H)-one hydrochloride were obtained.

Workup

  1. temperatureunder reflux for 24 h
  2. concentrationconcentrating the solvent under reduced pressure
  3. washwashed respectively with a saturated solution of NaHCO3 (2×20 ml), water (2×15 ml)
  4. dry with materialThe organic phase was then dried with Na2SO4
  5. customthe solvent was removed by evaporation at reduced pressure
  6. customThe solid raw product was then purified by flash chromatography on silica gel
  7. additiona mixture of chloroform
  8. customThe product thus purified
  9. dissolutionwas dissolved in a mixture of diethyl ether
  10. additionethanol in a ratio of 10:1 (10 ml) and treated at room temperature with 3M hydrochloric ethanol (0.33 ml)
  11. customThe solid thus formed
  12. filtrationwas filtered
  13. customcrystallized by a mixture isopropanol

Sources & evidence

ORD record
ord-8f919d6df7d54a3fb0d06cab6980137f
Source dataset
uspto-grants-2015_09
Patent number
US09120801B2

Reaction notes

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