Sodium Iodide → 4-(4-(4-(4-(3-Cyanopyridin-2-yl)piperazinyl)butyl)-phenyl)-2-amino-thiazole

HRID 329416Notes

Reaction equation

HRID 329416 reaction equation
Br.Cl[CH2:3][CH2:4][CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]([NH2:18])[S:16][CH:17]=2)=[CH:9][CH:8]=1.[C:19]([C:21]1[C:22]([N:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)=[N:23][CH:24]=[CH:25][CH:26]=1)#[N:20].C(N(C(C)C)CC)(C)C.C(=O)([O-])[O-].[Na+].[Na+].[I-].[Na+]>CC(CC(C)C)=O>[C:19]([C:21]1[C:22]([N:27]2[CH2:28][CH2:29][N:30]([CH2:3][CH2:4][CH2:5][CH2:6][C:7]3[CH:12]=[CH:11][C:10]([C:13]4[N:14]=[C:15]([NH2:18])[S:16][CH:17]=4)=[CH:9][CH:8]=3)[CH2:31][CH2:32]2)=[N:23][CH:24]=[CH:25][CH:26]=1)#[N:20]

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 27372032-(Piperazin-1-yl)pyridine-3-carbonitrileHCID 142114294-(4-(4-Chlorobutyl)phenyl)-2-aminothiazole hydrobromide

Product 1

HCID 147270324-(4-(4-(4-(3-Cyanopyridin-2-yl)piperazinyl)butyl)-phenyl)-2-amino-thiazole

Reagents, catalysts & solvents 1

HCID 7909Methyl Isobutyl KetoneSolvent

Procedure

To a 100 ml round-bottomed flask equipped with condenser and N2 inlet were added 2.37 g (6.81 mmol) 4-(4-(4-chlorobutyl)phenyl)-2-aminothiazole hydrobromide, 1.28 g (6.81 mmol) 3-cyano-2-piperazinylpyridine, 2.38 ml (13.6 mmol) diisopropylethylamine, 1.44 g (13.6 mmol) sodium carbonate, 2 mg sodium iodide, and 40 ml methylisobutylketone. The reaction was refluxed 4 days, cooled, and evaporated. The residue was triturated with ethyl acetate and the resulting solid chromatographed on silica gel with methylene chloride/ethyl acetate. The product fractions were dissolved in ethyl acetate, precipitated with ethyl acetate saturated with HCl, and the precipitate filtered and dried to give a solid, 1.84 g (55%), m.p. 155-162° C. NMR (DMSO-d6) 1.6-1.8 (m, 4H), 2.67 (t, 2H), 3.1-4.4 (m, 10H), 7.34 (s, 1H), 7.1-8.5 (m, 7H), 11.3 (bs, 2H).

Workup

  1. customTo a 100 ml round-bottomed flask equipped with condenser and N2 inlet
  2. temperatureThe reaction was refluxed 4 days
  3. temperaturecooled
  4. customevaporated
  5. customThe residue was triturated with ethyl acetate
  6. customthe resulting solid chromatographed on silica gel with methylene chloride/ethyl acetate
  7. dissolutionThe product fractions were dissolved in ethyl acetate
  8. customprecipitated with ethyl acetate saturated with HCl
  9. filtrationthe precipitate filtered
  10. customdried
  11. customto give a solid, 1.84 g (55%), m.p. 155-162° C

Sources & evidence

ORD record
ord-5c42cf72ae4944f3812cdc7ceaf40bae
Source dataset
uspto-grants-1990_01
Patent number
US04891375

Reaction notes

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