1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → N-[(1R*,2R*)-2-Aminocyclopentyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide hydrochloride

HRID 902839Notes

Reaction equation

HRID 902839 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][C:5]2[N:8]=[C:9]([C:11]([O-:13])=O)[S:10][C:4]=2[CH2:3]1.[Li+].[ClH:15].CN(C)CCCN=C=NCC.O.O[N:29]1[C:33]2C=[CH:35][CH:36]=[CH:37][C:32]=2[N:31]=N1>CN(C)C=O>[ClH:15].[NH2:29][C@@H:33]1[CH2:35][CH2:36][CH2:37][C@H:32]1[NH:31][C:11]([C:9]1[S:10][C:4]2[CH2:3][N:2]([CH3:1])[CH2:7][CH2:6][C:5]=2[N:8]=1)=[O:13]

Participants

5

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 23704331Lithium 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate

Product 1

HCID 18442877N-[(1R*,2R*)-2-Aminocyclopentyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide hydrochlorideYield 96.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The compound (175 mg) obtained in Referential Example 61 was dissolved in N,N-dimethylformamide (3 ml), and to the solution lithium 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate (purity: 90%, 258 mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (252 mg) and 1-hydroxybenzotriazole monohydrate (60 mg) were added. The mixture was stirred at room temperature for 2 days. The solvent was distilled off under reduced pressure using a pump, and methylene chloride and a saturated solution of sodium hydrogencarbonate were added to the residue to separate an organic layer. The resultant organic layer was washed with saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by flash column chromatography on silica gel (methylene chloride:methanol=47:3). The resultant pale yellow oil was dissolved in a ethanol solution (5 ml) of hydrochloric acid, and the solution was stirred at room temperature for 1 hour. Ethyl acetate was then added, and the solvent was distilled off under reduced pressure. Ethyl acetate was added to the residue to collect precipitate formed by filtration, thereby obtaining the title compound (120 mg).

Workup

  1. distillationThe solvent was distilled off under reduced pressure
  2. additiona saturated solution of sodium hydrogencarbonate were added to the residue
  3. customto separate an organic layer
  4. washThe resultant organic layer was washed with saturated aqueous solution of sodium chloride
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel (methylene chloride:methanol=47:3)
  8. dissolutionThe resultant pale yellow oil was dissolved in a ethanol solution (5 ml) of hydrochloric acid
  9. stirringthe solution was stirred at room temperature for 1 hour
  10. additionEthyl acetate was then added
  11. distillationthe solvent was distilled off under reduced pressure
  12. additionEthyl acetate was added to the residue
  13. customto collect precipitate
  14. customformed by filtration

Sources & evidence

ORD record
ord-1b2ab19890864d0c9a9b0f0c41027f9a
Source dataset
uspto-grants-2008_04
Patent number
US07365205B2

Reaction notes

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