Sodium Iodide → 4-(4-(2-(4-(3-Benzisothiazolyl)piperazinyl)ethyl)phenyl)-2-aminothiazole

HRID 329400Notes

Reaction equation

HRID 329400 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.[S:17]1[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[C:19]([N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)=[N:18]1.C(N(C(C)C)CC)(C)C.C(=O)([O-])[O-].[Na+].[Na+].[I-].[Na+]>C(OCC)(=O)C.CC(CC(C)C)=O>[S:17]1[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[C:19]([N:26]2[CH2:27][CH2:28][N:29]([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)[CH2:30][CH2:31]2)=[N:18]1

Participants

8

Reactant 5

HCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 27721443-(1-Piperazinyl)-1,2-benzisothiazoleHCID 147269834-(2-Chloroethyl)phenyl-2-aminothiazole hydrobromide

Product 1

HCID 147270044-(4-(2-(4-(3-Benzisothiazolyl)piperazinyl)ethyl)phenyl)-2-aminothiazole

Reagents, catalysts & solvents 2

HCID 7909Methyl Isobutyl KetoneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a 50 ml round-bottomed flask equipped with condenser and N2 inlet were added 2.4 g (7.53 mmol) of 4-(4-(2-chloroethyl)phenyl)-2-aminothiazole hydrobromide, 1.65 g (7.53 mmol) of N-(3-benzisothiazolyl) piperazine (prepared according to the method of U.S. Pat. No. 4,411,901), 1.3 ml (7.53 mmol) of diisopropylethylamine, 1.6 g (15.1 mmol) of sodium carbonate, 2 mg of sodium iodide, and 25 ml of methylisobutylketone. The reaction was heated at reflux for 5 days, cooled, evaporated, and taken up in ethyl acetate/water. The ethyl acetate layer was separated, washed with water and brine, dried over sodium sulfate, and evaporated. The residue was chromatographed on silica gel using ethyl acetate as eluent to give a solid. The solid was taken up in hot ethyl acetate, precipitated by addition of hydrochloride gas, the precipitate filtered, washed with ether, and dried to give a beige solid, 1.536 g (38%), m.p. >300° C. (dec.). NMR (DMSO-d6): 3.2-3.8 (m, 10H), 4.1 (m, 2H), 7.25 (s, 1H), 7.4-8.2 (m, 8H), 11.5 (bs, 2H).

Workup

  1. customTo a 50 ml round-bottomed flask equipped with condenser and N2 inlet
  2. customprepared
  3. temperatureThe reaction was heated
  4. temperatureat reflux for 5 days
  5. temperaturecooled
  6. customevaporated
  7. customThe ethyl acetate layer was separated
  8. washwashed with water and brine
  9. dry with materialdried over sodium sulfate
  10. customevaporated
  11. customThe residue was chromatographed on silica gel
  12. customto give a solid
  13. customprecipitated by addition of hydrochloride gas
  14. filtrationthe precipitate filtered
  15. washwashed with ether
  16. customdried
  17. customto give a beige solid, 1.536 g (38%), m.p. >300° C. (dec.)

Sources & evidence

ORD record
ord-d5387d7bd46a4e8baed9c4416c826624
Source dataset
uspto-grants-1990_01
Patent number
US04891375

Reaction notes

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