4-Methylmorpholine → N-(5-chloropyridin-2-yl)-2-(2-oxo-3-phenylpiperidin-1-yl)acetamide

HRID 1667231Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1667231
[O:1]=[C:2]1[CH:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][N:3]1[CH2:14][C:15]([OH:17])=O.C(Cl)(=O)C(Cl)=O.[Cl:24][C:25]1[CH:26]=[CH:27][C:28]([NH2:31])=[N:29][CH:30]=1.CN1CCOCC1>ClCCl.CN(C)C=O>[Cl:24][C:25]1[CH:26]=[CH:27][C:28]([NH:31][C:15](=[O:17])[CH2:14][N:3]2[CH2:4][CH2:5][CH2:6][CH:7]([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:2]2=[O:1])=[N:29][CH:30]=1

Komponenten

7

Edukt 4

HCID 79724-MethylmorpholineHCID 65578Oxalyl chlorideHCID 661742-Amino-5-chloropyridineHCID 673587022-(2-Oxo-3-phenylpiperidin-1-yl)acetic acid

Produkt 1

HCID 67444597N-(5-chloropyridin-2-yl)-2-(2-oxo-3-phenylpiperidin-1-yl)acetamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 2-(2-oxo-3-phenylpiperidin-1-yl)acetic acid (0.100 g, 0.429 mmol; Example 91D) in dichloromethane (0.5 mL) was added oxalyl chloride (2.0 Min dichloromethane) (0.322 mL, 0.643 mmol) and a catalytic amount of N,N-dimethylformamide. After stirring for 30 minutes at 0° C., a reddish solution resulted. The reaction was concentrated, the residue was dissolved in dichloromethane (1 mL) and 5-chloropyridin-2-amine (0.047 g, 0.364 mmol) was added followed by N-methylmorpholine (0.071 mL, 0.643 mmol). After stirring for 1 hour, the reaction was loaded onto a silica gel column (SF15-24, Analogix®) and the product was eluted using a gradient of 25% ethyl acetate/hexanes to 70% ethyl acetate/hexanes over 30 minutes (Flow=30 mL/minute). Some color streaked through the column, so a second column was run under identical conditions to give the title compound. 1H NMR (300 MHz, CDCl3) δ 8.84 (s, 1H), 8.23 (d, J=2.7, 1H), 8.14 (d, J=8.8, 1H), 7.65 (dd, J=2.6, 8.9, 1H), 7.42-7.13 (m, 5H), 4.34-4.15 (m, 2H), 3.78 (dd, J=6.0, 7.9, 1H), 3.71-3.47 (m, 2H), 2.33-2.14 (m, 1H), 1.99 (m, 3H); MS (ESI+) m/z 344.0 (M+H)+.

Aufarbeitung

  1. customa reddish solution resulted
  2. concentrationThe reaction was concentrated
  3. dissolutionthe residue was dissolved in dichloromethane (1 mL)
  4. stirringAfter stirring for 1 hour
  5. washthe product was eluted
  6. customover 30 minutes

Quellen und Nachweise

ORD-Eintrag
ord-51834cf2b01b49968586097a4d1aa293
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08044069B2

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