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 546412Notes

Reaction equation

HRID 546412 reaction equation
C(O[C:6]([NH:8][C@@H:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[NH2:14])=[O:7])(C)(C)C.[CH3:15][N:16]1[CH2:21][CH2:20][C:19]2[N:22]=[C:23](C([O-])=O)[S:24][C:18]=2[CH2:17]1.[Li+].[ClH:29].CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[ClH:29].[CH3:15][N:16]1[CH2:21][CH2:20][C:19]2[N:22]=[C:23]([C:6]([NH:8][C@@H:9]3[CH2:13][CH2:12][CH2:11][C@H:10]3[NH2:14])=[O:7])[S:24][C:18]=2[CH2:17]1

Participants

6

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 17040217rac-tert-butyl N-((1R,2R)-2-aminocyclopentyl)carbamateHCID 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 43.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(±)-trans-N-tert-Butoxycarbonyl-1,2-cyclopentane-diamine (175 mg) 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-ethyl-carbodiimide hydrochloride (252 mg) and 1-hydroxybenzo-triazole 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 dichloromethane 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 saline and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by medium-pressure flash column chromatography on silica gel (dichloromethane:methanol=47:3). The resultant pale yellow oil was dissolved in a saturated 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 by filtration, thereby obtaining the title compound (120 mg) as a pale yellow solid.

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 saline
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe residue was purified by medium-pressure flash column chromatography on silica gel (dichloromethane:methanol=47:3)
  8. dissolutionThe resultant pale yellow oil was dissolved in a saturated 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. filtrationby filtration

Sources & evidence

ORD record
ord-592aeb89532e43e79a2f85db457016af
Source dataset
uspto-grants-2011_05
Patent number
US07935824B2

Reaction notes

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