Sodium Iodide → 4-(4-(2-(4-(8-Quinolyl)piperazinyl)ethyl)phenyl)-2-aminothiazole

HRID 329401Notes

Reaction equation

HRID 329401 reaction equation
Br.Cl[CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[C:13]([NH2:16])[S:14][CH:15]=2)=[CH:7][CH:6]=1.[N:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][C:25]=2[N:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)[CH:20]=[CH:19][CH:18]=1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[Na+]>C(OCC)(=O)C.O.C(O)C>[N:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][C:25]=2[N:27]2[CH2:28][CH2:29][N:30]([CH2:3][CH2:4][C:5]3[CH:10]=[CH:9][C:8]([C:11]4[N:12]=[C:13]([NH2:16])[S:14][CH:15]=4)=[CH:7][CH:6]=3)[CH2:31][CH2:32]2)[CH:20]=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 118307868-(1-piperazinyl)QuinolineHCID 147269834-(2-Chloroethyl)phenyl-2-aminothiazole hydrobromide

Product 1

HCID 147270064-(4-(2-(4-(8-Quinolyl)piperazinyl)ethyl)phenyl)-2-aminothiazole

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 22728543Water ethylacetateSolvent

Procedure

To a 35 ml round-bottomed flask equipped with condenser and N2 inlet were added 0.746 g (2.34 mmol) of 4-(4-(2-chloroethyl)phenyl-2-aminothiazole hydrobromide, 0.50 g (2.34 mmol) of N-(8-quinolyl)piperazine (prepared from 8-aminoquinoline by reaction with diethanolamine in hydrobromide at 200° C.), 0.621 g (5.86 mmol) of sodium carbonate, 50 mg of sodium iodide, and 10 ml of ethanol. The reaction was heated at reflux for 25 hours, cooled, and the reaction mixture taken up in ethyl acetate/water. The layers were separated, the ethyl acetate layer dried and evaporated. The residue was chromatographed on silica gel using chloroform/methanol as eluent and the product fractions combined in methanol and precipitated with a solution of hydrochloride in ether. The precipitate was stirred with ether/methanol to afford a crystalline solid, m.p. >225° C., 277 mg (27%). NMR (free base in CDCl3): 2.8 (m, 8H), 3.5 (m, 4H), 7.0-8.2 (m, 11H).

Workup

  1. customTo a 35 ml round-bottomed flask equipped with condenser and N2 inlet
  2. temperatureThe reaction was heated
  3. temperatureat reflux for 25 hours
  4. temperaturecooled
  5. customThe layers were separated
  6. dry with materialthe ethyl acetate layer dried
  7. customevaporated
  8. customThe residue was chromatographed on silica gel
  9. customprecipitated with a solution of hydrochloride in ether
  10. customto afford a crystalline solid, m.p. >225° C., 277 mg (27%)

Sources & evidence

ORD record
ord-73780695d59245b380b2a0822a066e6b
Source dataset
uspto-grants-1990_01
Patent number
US04891375

Reaction notes

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