5-Chloro-1H-indole-2-carboxylic acid → (+/-)-trans-N1-[(5-Chloroindol-2-yl)carbonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclopentanediamine hydrochloride

HRID 459553Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 459553
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([OH:13])=O)=[CH:5]2.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.Cl.[CH3:38][N:39]1[CH2:44][CH2:43][C:42]2[N:45]=[C:46]([C:48]([NH:50][C@@H:51]3[CH2:55][CH2:54][CH2:53][C@H:52]3[NH2:56])=[O:49])[S:47][C:41]=2[CH2:40]1>CN(C)C=O.C(N(CC)CC)C>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([NH:56][C@@H:52]1[CH2:53][CH2:54][CH2:55][C@H:51]1[NH:50][C:48]([C:46]1[S:47][C:41]3[CH2:40][N:39]([CH3:38])[CH2:44][CH2:43][C:42]=3[N:45]=1)=[O:49])=[O:13])=[CH:5]2

Komponenten

7

Edukt 4

HCID 826935-Chloro-1H-indole-2-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 18442877N-[(1R*,2R*)-2-Aminocyclopentyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide hydrochloride

Produkt 1

HCID 45263647(+/-)-trans-N1-[(5-Chloroindol-2-yl)carbonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclopentanediamine hydrochlorideAusbeute 107,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

5-Chloroindole-2-carboxylic acid (80 mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (98 mg), 1-hydroxybenzotriazole monohydrate (23 mg) and triethylamine (141 μl) were added to a solution with (±)-trans-N-[(5-methyl-4,5,6,7-tetrahydrothiazolo-[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclopentanediamine hydrochloride (120 mg) dissolved in N,N-dimethylformamide (5 ml), and the mixture was stirred at room temperature for 3 days. The solvent was distilled off under reduced pressure, and dichloromethane and a saturated aqueous solution of sodium hydrogencarbonate were added to the residue to conduct liquid separation. The resultant organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by flash column chromatography on silica gel (dichloromethane:methanol=93:7). After dichloromethane (5 ml) and a 1N ethanol solution (282 μl) of hydrochloric acid were added to the thus-obtained pale yellow solid. Ethyl acetate was added, solvent was distilled off under reduced pressure and precipitate formed was collected by filtration to obtain the title compound (109 mg) as a pale yellow solid.

Aufarbeitung

  1. distillationThe solvent was distilled off under reduced pressure, and dichloromethane
  2. additiona saturated aqueous solution of sodium hydrogencarbonate were added to the residue
  3. customliquid separation
  4. dry with materialThe resultant organic layer was dried over anhydrous sodium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customthe residue was purified by flash column chromatography on silica gel (dichloromethane:methanol=93:7)
  7. additionAfter dichloromethane (5 ml) and a 1N ethanol solution (282 μl) of hydrochloric acid were added to the thus-obtained pale yellow solid
  8. additionEthyl acetate was added
  9. distillationsolvent was distilled off under reduced pressure and precipitate
  10. customformed
  11. filtrationwas collected by filtration

Quellen und Nachweise

ORD-Eintrag
ord-f29bac67614c4c33be16560ad4ec7946
Quelldatensatz
uspto-grants-2007_03
Patentnummer
US07192968B2

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