Potassium Carbonate → Gsk-1292263

HRID 423546Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 423546
CS([O:5][CH2:6][CH:7]1[CH2:12][CH2:11][N:10]([C:13]2[O:17][N:16]=[C:15]([CH:18]([CH3:20])[CH3:19])[N:14]=2)[CH2:9][CH2:8]1)(=O)=O.[CH3:21][S:22]([C:25]1[CH:30]=[CH:29][C:28]([C:31]2[N:36]=[CH:35][C:34](O)=[CH:33][CH:32]=2)=[CH:27][CH:26]=1)(=[O:24])=[O:23].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:20][CH:18]([C:15]1[N:14]=[C:13]([N:10]2[CH2:9][CH2:8][CH:7]([CH2:6][O:5][C:34]3[CH:33]=[CH:32][C:31]([C:28]4[CH:29]=[CH:30][C:25]([S:22]([CH3:21])(=[O:23])=[O:24])=[CH:26][CH:27]=4)=[N:36][CH:35]=3)[CH2:12][CH2:11]2)[O:17][N:16]=1)[CH3:19]

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 532295926-(4-(Methylsulfonyl)phenyl)pyridin-3-olHCID 57930198(1-(3-Isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)methyl methanesulfonate

Produkt 1

HCID 24996872Gsk-1292263Ausbeute 85,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of {1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl methanesulfonate (82.3 g, 271 mmol), 6-[4-(methylsulfonyl)phenyl]-3-pyridinol (71.0 g, 285 mmol), powdered potassium carbonate (118 g, 855 mmol) and N,N-dimethylformamide (750 mL) was mechanically stirred and heated at 80° C. under nitrogen for 20 h. The reaction was cooled to ambient temperature, poured onto ice water (3 L) and allowed to stand for 1 h. The resulting solid was filtered, rinsed with water (2×500 mL) and air-dried. The solid was taken up in dichloromethane (300 mL) and methanol (500 mL). The dichloromethane was slowly removed via rotovap at 55° C. The methanol solution was allowed to stand at ambient temperature for 16 h. The resulting crystalline solid was filtered, rinsed with cold methanol and dried under vacuum at 60° C. for 18 h to afford the desired product (105.7 g, 84%) as a light tan solid. 1H NMR (400 MHz, CDCl3): δ 8.41 (d, 1H, J=2.8 Hz), 8.13 (d, 2H, J=8.6 Hz), 8.01 (d, 2H, J=8.6 Hz), 7.74 (d, 1H, J=8.7 Hz), 7.29 (dd, 1H, Ja=8.7 Hz, Jb=3.0 Hz), 4.24 (d, 2H, J=13.1 Hz), 3.95 (d, 2H, J=6.2 Hz), 3.17-3.04 (m, 5H), 2.94-2.84 (m, 1H), 2.11 (bs, 1H), 1.97 (d, 2H, J=12.6 Hz), 1.54-1.42 (m, 2H), 1.29 (d, 6H, J=7.0 Hz); LRMS (ESI), m/z 457 (M+H).

Aufarbeitung

  1. temperatureThe reaction was cooled to ambient temperature
  2. additionpoured onto ice water (3 L)
  3. filtrationThe resulting solid was filtered
  4. washrinsed with water (2×500 mL)
  5. customair-dried
  6. customThe dichloromethane was slowly removed via rotovap at 55° C
  7. waitto stand at ambient temperature for 16 h
  8. filtrationThe resulting crystalline solid was filtered
  9. washrinsed with cold methanol
  10. customdried under vacuum at 60° C. for 18 h

Quellen und Nachweise

ORD-Eintrag
ord-7c8c3d183d3744e4ab79d6da95d44ea6
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08101634B2

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