3-Aminopyridine → 1-pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

HRID 1093842Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1093842
CCN(C(C)C)C(C)C.[N:10]1[CH:15]=[CH:14][CH:13]=[C:12]([N:16]2[CH:20]=[C:19]([C:21]([NH:23][CH2:24][C:25]([OH:27])=O)=[O:22])[N:18]=[N:17]2)[CH:11]=1.NC1C=NC=CC=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[F:57][C:58]1[CH:70]=[CH:69][C:68]([F:71])=[CH:67][C:59]=1[O:60][CH:61]1[CH2:66][CH2:65][NH:64][CH2:63][CH2:62]1>CN(C=O)C.O>[F:57][C:58]1[CH:70]=[CH:69][C:68]([F:71])=[CH:67][C:59]=1[O:60][CH:61]1[CH2:62][CH2:63][N:64]([C:25](=[O:27])[CH2:24][NH:23][C:21]([C:19]2[N:18]=[N:17][N:16]([C:12]3[CH:11]=[N:10][CH:15]=[CH:14][CH:13]=3)[CH:20]=2)=[O:22])[CH2:65][CH2:66]1

Komponenten

9

Edukt 6

HCID 100093-AminopyridineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 66591553HCID 66591553, VerbindungHCID 66592012[(1-pyridin-3-yl-1H-[1,2,3]triazole-4-carbonyl)-amino]-acetic acid

Produkt 1

HCID 578744761-pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amideAusbeute 46,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

DIPEA (135.9 mg, 1.05 mmol) was added to a stirred solution of [(1-pyridin-3-yl-1H-[1,2,3]triazole-4-carbonyl)-amino]-acetic acid (prepared by the method used for the synthesis of Intermediate 64, starting from 3-aminopyridine, and subsequently, application of Step 3 of the General Scheme) (65 mg, 0.26 mmol) in DMF (2 mL) followed by HOBt (39 mg, 0.29 mmol) and EDCI (101 mg, 0.52 mmol). After 2 minutes of stirring, 4-(2,5-difluoro-phenoxy)-piperidine hydrochloride (prepared by the method used for the synthesis of Intermediate 15) (65.6 mg, 0.26 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added and the resultant was extracted with DCM. The organic layer was collected and dried over sodium sulfate and concentrated under reduced pressure The residue obtained was purified by stirring in mixture of 30% EtOAc in hexane (10 mL), H2O (0.5 mL) and MeOH (0.5 mL) for 30 minutes. Filtered the mixture to afford 54 mg (46.5% Yield) of 1-pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 443.16, 92.48%. 1H NMR (300 MHz, DMSO-d6): δ 9.45 (s, 1H), 9.2 (d, 1H), 8.75 (m, 1H), 8.5 (t, 1H), 8.4 (m, 1H), 7.7 (q, 1H), 7.32-7.2 (m, 2H), 6.7-6.4 (m, 1H), 4.8-4.7 (m, 1H), 4.25 (d, 2H), 4.0-3.8 (m, 1H), 3.8-3.7 (m, 1H), 3.4 (m, 1H), 3.3 (m, 1H), 2.1-1.9 (m, 2H), 1.8-1.5 (m, 2H).

Aufarbeitung

  1. customprepared by the method
  2. additionwas added
  3. stirringthe resulting mixture was stirred at room temperature overnight
  4. extractionthe resultant was extracted with DCM
  5. customThe organic layer was collected
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure The residue
  8. customobtained
  9. customwas purified
  10. stirringby stirring in mixture of 30% EtOAc in hexane (10 mL), H2O (0.5 mL) and MeOH (0.5 mL) for 30 minutes
  11. filtrationFiltered the mixture

Quellen und Nachweise

ORD-Eintrag
ord-d15fdfec5bc241ad9ef8939f2877c4b6
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08129376B2

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