4-(2-Pyrimidinyl)-1-piperazinebutanamine → 3-[4-[4-(2-Pyrimidinyl)-1-piperazinyl]butyl]-9-oxa-3-azabicyclo[3.3.1]nonane-2,4-dione

HRID 1253266Notes

Reaction equation

HRID 1253266 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[N:28]=[CH:27][CH:26]=[CH:25][N:24]=2)[CH2:19][CH2:18]1>C(Cl)Cl>[N:24]1[CH:25]=[CH:26][CH:27]=[N:28][C:23]=1[N:20]1[CH2:21][CH2:22][N:17]([CH2:16][CH2:15][CH2:14][CH2:13][N:12]2[C:7](=[O:9])[CH:6]3[O:1][CH:2]([CH2:3][CH2:4][CH2:5]3)[C:10]2=[O:11])[CH2:18][CH2:19]1

Participants

4

Reactant 2

HCID 128407054-(2-Pyrimidinyl)-1-piperazinebutanamineHCID 542819683,9-Dioxabicyclo[3.3.1]nonane-2,4-dione

Product 1

HCID 141563733-[4-[4-(2-Pyrimidinyl)-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 (3.0 g., 19 mmole) and 1-(4-aminobutyl)-4-(2-pyrimidinyl)piperazine (4.98 g., 21 mmole) were combined and stirred for 30 minutes in 200 ml. of methylene chloride. The solvent was removed in vacuum and replaced with 300 ml. of xylene. The mixture was refluxed for 48 hours with water removal via a Dean-Stark trap. The solvent was again removed in vacuum and the residue was column chromatographed on 100 g. of silica with a gradient elution beginning with chloroform and ending with 5% ethanol in chloroform. The relevant fractions were combined and evaporated and the product crystallized from isopropanol with the addition of 4N isopropanolic HCl and ether. A second crystallization from isopropanol gave 1.9 g. of the title compound as the dihydrochloride, hemihydrate; m.p. 232°-233° C. (d).

Workup

  1. customThe solvent was removed in vacuum
  2. temperatureThe mixture was refluxed for 48 hours with water removal via a Dean-Stark trap
  3. customThe solvent was again removed in vacuum
  4. customchromatographed on 100 g
  5. washof silica with a gradient elution
  6. customevaporated
  7. customthe product crystallized from isopropanol with the addition of 4N isopropanolic HCl and ether
  8. customA second crystallization from isopropanol
  9. customgave 1.9 g

Sources & evidence

ORD record
ord-7dbe4f404d654c39838fd65c2ae6757c
Source dataset
uspto-grants-1988_05
Patent number
US04748240

Reaction notes

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