Hydrochloric Acid → (10H-Pyrazino[2,3-b][1,4]benzothiazin-8-yl)acetamidine

HRID 1059447Notes

Reaction equation

HRID 1059447 reaction equation
[Cl-].[NH4+:2].C[Al](C)C.[N:7]1[C:16]2[NH:15][C:14]3[CH:17]=[C:18]([CH2:21][C:22]#[N:23])[CH:19]=[CH:20][C:13]=3[S:12][C:11]=2[N:10]=[CH:9][CH:8]=1.Cl>CCCCCC.C(OCC)(=O)C.C1(C)C=CC=CC=1>[N:7]1[C:16]2[NH:15][C:14]3[CH:17]=[C:18]([CH2:21][C:22]([NH2:2])=[NH:23])[CH:19]=[CH:20][C:13]=3[S:12][C:11]=2[N:10]=[CH:9][CH:8]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 25517Ammonium Chloride2×HCID 16682925TrimethylaluminumHCID 1867021210H-Pyrazino[2,3-b][1,4]benzothiazine-8-acetonitrile

Product 1

HCID 18670382(10H-Pyrazino[2,3-b][1,4]benzothiazin-8-yl)acetamidineYield 38.6%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

2.68 g of ammonium chloride was added to 20 ml of dry toluene in a nitrogen atmosphere. Then 36.5 ml of a 15% solution of trimethylaluminum in n-hexane was added thereto under stirring and ice-cooling. The reaction mixture was brought back to room temperature and 70 ml of dry toluene was further added. The resulting mixture was subjected to ultrasonication until the ammonium chloride disappeared completely. A 60 ml portion of the solution thus obtained was taken and 1.5 g of (10H-pyrazino[2,3-b][1,4]benzothiazin-8-yl)acetonitrile was added thereto. The obtained mixture was heated under reflux for 18 hours. After bringing back to room temperature, the reaction mixture was distributed into ethyl acetate and dilute hydrochloric acid and repeatedly extracted with water. The aqueous layer was washed with methylene chloride and the solvent contained in the solution was eliminated under reduced pressure. The obtained residue was purified by High-porous gel column chromatography (CHP20, mfd. by Mitsubishi Chemical Industries, Ltd., 75-15μ) (eluted with water/methanol) to thereby give 620 mg of the title compound as yellow crystals.

Workup

  1. temperatureice-cooling
  2. customwas brought back to room temperature
  3. customA 60 ml portion of the solution thus obtained
  4. temperatureThe obtained mixture was heated
  5. temperatureunder reflux for 18 hours
  6. customAfter bringing back to room temperature
  7. extractionrepeatedly extracted with water
  8. washThe aqueous layer was washed with methylene chloride
  9. customThe obtained residue was purified by High-porous gel column chromatography (CHP20, mfd. by Mitsubishi Chemical Industries, Ltd., 75-15μ) (eluted with water/methanol)

Sources & evidence

ORD record
ord-5d900e6851c54255a68a5d1c927e1b03
Source dataset
uspto-grants-2003_02
Patent number
US06518423B1

Reaction notes

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