O-Xylene → HCID 14370164, compound

HRID 621781Notes

Reaction equation

HRID 621781 reaction equation
[CH:1]12[CH2:8][CH:7]=[CH:6][CH:5]1[CH:4]([C:9]([OH:11])=O)[CH2:3][CH:2]2[C:12]([OH:14])=O.C(OC(=O)C)(=O)C.[NH2:22][CH2:23][CH2:24][CH2:25][CH2:26][N:27]1[CH2:32][CH2:31][N:30]([C:33]2[N:38]=[CH:37][CH:36]=[CH:35][N:34]=2)[CH2:29][CH2:28]1.C1(C)C(C)=CC=CC=1>O>[N:34]1[CH:35]=[CH:36][CH:37]=[N:38][C:33]=1[N:30]1[CH2:31][CH2:32][N:27]([CH2:26][CH2:25][CH2:24][CH2:23][N:22]2[C:9](=[O:11])[CH:4]3[CH2:3][CH:2]([CH:1]4[CH2:8][CH:7]=[CH:6][CH:5]43)[C:12]2=[O:14])[CH2:28][CH2:29]1

Participants

6

Reactant 4

HCID 7237O-XyleneHCID 7918Acetic AnhydrideHCID 128407054-(2-Pyrimidinyl)-1-piperazinebutanamineHCID 13700967HCID 13700967, compound

Product 1

HCID 14370164HCID 14370164, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Bicyclo[3.3.0]oct-6-ene-2,4-dicarboxylic acid (12.6 g., 67 mmol.) was converted to 4.24 g. of anhydride by treatment with excess acetic anhydride as in Example 1. In this instance, however, the anhydride was purified by extraction of the dark residual gum with hexane, filtration, and evaporation in vacuo. The anhydride was combined with 6.0 g. (24 mmols) of 1-(4-aminobutyl)-4-(2-pyrimidinyl)piperazine in 250 ml. of xylene and refluxed under N2 for 24 hours with water separation via a Dean-Stark trap. The supernatant liquid was removed at this point and replaced with an additional 150 ml. of xylene. Reflux under N2 was continued for 24 hours. The combined xylene solutions were then evaporated and the residue column chromatographed on 250 g. of silica gel with a gradient elution beginning with CHCl3 and ending with 10% CH3OH/CHCl3. The product-containing fractions were combined and evaporated and the residue crystallized from isopropanol with the addition of 4N HCl in isopropanol to give 3.25 g. of white solid title compound as the dihydrochloride salt, m.p. 232°-234° C.

Workup

  1. filtrationIn this instance, however, the anhydride was purified by extraction of the dark residual gum with hexane, filtration, and evaporation in vacuo
  2. customThe supernatant liquid was removed at this point
  3. temperatureReflux under N2
  4. customThe combined xylene solutions were then evaporated
  5. customthe residue column chromatographed on 250 g
  6. washof silica gel with a gradient elution
  7. customevaporated
  8. customthe residue crystallized from isopropanol with the addition of 4N HCl in isopropanol
  9. customto give 3.25 g

Sources & evidence

ORD record
ord-256605df382c4278aa71badfef885c94
Source dataset
uspto-grants-1989_04
Patent number
US04824999

Reaction notes

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