Phenol → HCID 20131119, compound

HRID 542208Notes

Reaction equation

HRID 542208 reaction equation
O.[NH2:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[C:5]([N:17]2[CH2:22][CH2:21][N:20]([C:23]3[CH:28]=[CH:27][N:26]=[C:25]([Cl:29])[N:24]=3)[CH2:19][CH2:18]2)[CH:4]=1.NC1[C:40]2[C:35](=[CH:36][C:37](OC)=[C:38]([O:41]C)[CH:39]=2)N=C(N2CCN(C3C=CN=C([Cl:57])N=3)CC2)C=1.C1(O)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CC(C)CC(=O)C.CO.C(Cl)Cl>[ClH:29].[ClH:57].[NH2:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[C:5]([N:17]2[CH2:22][CH2:21][N:20]([C:23]3[CH:28]=[CH:27][N:26]=[C:25]([O:41][C:38]4[CH:39]=[CH:40][CH:35]=[CH:36][CH:37]=4)[N:24]=3)[CH2:19][CH2:18]2)[CH:4]=1

Participants

8

Reactant 4

HCID 996Phenol2×HCID 4875Potassium Iodide2×HCID 11430Potassium Carbonate2×HCID 88639602HCID 88639602, compound

Product 1

HCID 20131119HCID 20131119, compoundYield 125.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 7909Methyl Isobutyl KetoneSolvent

Procedure

4-Amino-2-[4-(2-chloropyrimidin-4-yl)piperazin-1-yl]-6,7-dimethoxyquinoline hemihydrate (0.32 g), phenol (0.15 g), anhydrous potassium carbonate (0.22 g) and potassium iodide (catalytic trace) in 4-methyl-2-pentanone (125 ml) were stirred under reflux for 18 hours. Further portions of phenol, anhydrous potassium carbonate and potassium iodide were then added thrice at 8 hour intervals, followed by a final 18 hours refluxing. After cooling, methylene chloride (50 ml) and methanol (20 ml) were added and the reaction mixture filtered. The filtrate was evaporated in vacuo and the residue dissolved in methylene chloride, washed with water, dried (MgSO4) and evaporated in vacuo. Chromatography on silica (Merck 9385, 40 g) eluting with methylene chloride/methanol (100:0→88:12) followed by treatment of the product with ethereal hydrogen chloride and recrystallisation from isopropanol gave 4-amino-6,7-dimethoxy-2-[4-(2-phenoxypyrimidin-4-yl)piperazin-1-yl]quinoline dihydrochloride (0.26 g), m.p. 199°-201° (d).

Workup

  1. temperatureunder reflux for 18 hours
  2. custom18 hours
  3. temperaturerefluxing
  4. temperatureAfter cooling
  5. filtrationthe reaction mixture filtered
  6. customThe filtrate was evaporated in vacuo
  7. dissolutionthe residue dissolved in methylene chloride
  8. washwashed with water
  9. dry with materialdried (MgSO4)
  10. customevaporated in vacuo
  11. washChromatography on silica (Merck 9385, 40 g) eluting with methylene chloride/methanol (100:0→88:12)
  12. customfollowed by treatment of the product with ethereal hydrogen chloride and recrystallisation from isopropanol

Sources & evidence

ORD record
ord-25933165014449aab7f1bdc1b165e947
Source dataset
uspto-grants-1987_04
Patent number
US04656174

Reaction notes

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