Ethyl Acetate → HCID 53482858, compound

HRID 2272930Notes

Reaction equation

HRID 2272930 reaction equation
[C:1]1(=[O:14])[C:13]2[N:5]([N:6]=[C:7]3[C:12]=2[CH:11]=[CH:10][CH:9]=[CH:8]3)[CH2:4][CH2:3][NH:2]1.[H-].[Na+].[Cl:17][CH2:18][CH2:19][CH2:20][N:21]1[CH2:26][CH2:25][CH:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:23][CH2:22]1.C(OCC)(=O)C>O1CCCC1.CN(C)C=O>[ClH:17].[C:27]1([CH:24]2[CH2:23][CH2:22][N:21]([CH2:20][CH2:19][CH2:18][N:2]3[CH2:3][CH2:4][N:5]4[N:6]=[C:7]5[C:12]([CH:11]=[CH:10][CH:9]=[CH:8]5)=[C:13]4[C:1]3=[O:14])[CH2:26][CH2:25]2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 2036891-(3-Chloropropyl)-4-phenylpiperidineHCID 25102390HCID 25102390, compound

Product 1

HCID 53482858HCID 53482858, compoundYield 23.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 3,4-dihydropyrazino[1,2-b]indazol-1(2H)-one (375 mg; 2.0 mmol) in a mixture of tetrahydrofuran:dimethylformamide (DMF) in a ratio of 1:1 (4 ml) was added drop wise to a suspension of NaH 55% in mineral oil (104 mg; 2.4 mmol) in anhydrous tetrahydrofuran (THF), kept stirred at room temperature under argon atmosphere. The mixture was kept under stirring at the same temperature under inert atmosphere for 1 h; then, a solution of 1-(3-chloropropyl)-4-phenylpiperidine (4.4 g; 0.015 mol) in DMF (25 ml) was slowly added. Once the additions were over, the mixture was heated at the reflux temperature for 6 h. The reaction was then stopped by cooling the mixture to room temperature and by adding ethyl acetate (10 ml). The mixture was then filtered through a silica gel pad, then the solvent was removed by evaporation at reduced pressure. The residue was purified by flash chromatography on silica gel, using a mixture of chloroform:methanol in a ratio of 9:1 as eluent. The product thus purified was dissolved in a mixture of diethyl ether:ethanol in a ratio of 10:1 (10 ml) and processed at room temperature with 3M HCl in ethanol (0.33 ml). The solid thus formed was filtered and crystallized from a mixture of isopropanol:diisopropyl ether in a ratio 1:1. Thus, 197 mg of 2-[3-(4-phenylpiperidin-1-yl)propyl]-3,4-dihydropyrazino[1,2-b]indazol-1(2H)-one hydrochloride were obtained.

Workup

  1. stirringunder stirring at the same temperature under inert atmosphere for 1 h
  2. temperaturewas heated at the reflux temperature for 6 h
  3. temperatureby cooling the mixture to room temperature
  4. filtrationThe mixture was then filtered through a silica gel pad
  5. customthe solvent was removed by evaporation at reduced pressure
  6. customThe residue was 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. customprocessed at room temperature with 3M HCl in ethanol (0.33 ml)
  11. customThe solid thus formed
  12. filtrationwas filtered
  13. customcrystallized from a mixture of isopropanol

Sources & evidence

ORD record
ord-1e63e5bf6798474ba22ad7fe6f8611ec
Source dataset
uspto-grants-2015_09
Patent number
US09120801B2

Reaction notes

Loading…