4-[4-(6-Chloropyrazin-2-yl)piperazin-1-yl]butan-1-amine → 3-[4-[4-(6-Chloro-2-pyrazinyl)-1-piperazinyl]butyl]-9-oxa-3-azabicyclo[3.3.1]nonane-2,4-dione

HRID 1253268Notes

Reaction equation

HRID 1253268 reaction equation
[O:1]1[CH:6]2[C:7]([O:9][C:10](=[O:11])[CH:2]1[CH2:3][CH2:4][CH2:5]2)=O.[NH2:12][CH2:13][CH2:14][CH2:15][CH2:16][N:17]1[CH2:22][CH2:21][N:20]([C:23]2[CH:28]=[N:27][CH:26]=[C:25]([Cl:29])[N:24]=2)[CH2:19][CH2:18]1>C(Cl)Cl>[Cl:29][C:25]1[N:24]=[C:23]([N:20]2[CH2:19][CH2:18][N:17]([CH2:16][CH2:15][CH2:14][CH2:13][N:12]3[C:7](=[O:9])[CH:6]4[O:1][CH:2]([CH2:3][CH2:4][CH2:5]4)[C:10]3=[O:11])[CH2:22][CH2:21]2)[CH:28]=[N:27][CH:26]=1

Participants

4

Reactant 2

HCID 140865264-[4-(6-Chloropyrazin-2-yl)piperazin-1-yl]butan-1-amineHCID 542819683,9-Dioxabicyclo[3.3.1]nonane-2,4-dione

Product 1

HCID 141563773-[4-[4-(6-Chloro-2-pyrazinyl)-1-piperazinyl]butyl]-9-oxa-3-azabicyclo[3.3.1]nonane-2,4-dione

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Tetrahydropyran-2,6-dicarboxylic anhydride (3.12 g., 20 mmole) and 1-(4-aminobutyl)-4-(6-chloro-2-pyrazinyl)piperazine (5.94 g., 22 mmole) were combined in 200 ml. of methylene chloride and stirred for 30 minutes at room temperature. The solvent was removed in vacuum and replaced with 350 ml. of xylene. The mixture was refluxed for 50 hours with water removal via a Dean-Stark trap. The xylene was evaporated and the residue was filtered through 75 g. of silica gel with 2% ethanol/chloroform. The product was concentrated in vacuum and crystallized from isopropanol with the addition of 4N isopropanolic HCl. A second recrystallization from methanol gave 4.18 g. of the title compound as the monohydrochloride; m.p. 252°-253° C.

Workup

  1. customThe solvent was removed in vacuum
  2. temperatureThe mixture was refluxed for 50 hours with water removal via a Dean-Stark trap
  3. customThe xylene was evaporated
  4. filtrationthe residue was filtered through 75 g
  5. concentrationThe product was concentrated in vacuum
  6. customcrystallized from isopropanol with the addition of 4N isopropanolic HCl
  7. customA second recrystallization from methanol
  8. customgave 4.18 g

Sources & evidence

ORD record
ord-f263cbc2a829490da1aeec851e975a14
Source dataset
uspto-grants-1988_05
Patent number
US04748240

Reaction notes

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