Tetrahydrofuran → 7-chloro-1-{1-[(3-fluoro-2'-{[(1R)-3-hydroxy-1-methylpropyl]oxy}biphenyl-4-yl)carbonyl]piperidin-4-yl}-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-one

HRID 1026566Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1026566
O1CCCC1.[Si]([O:23][CH2:24][CH2:25][C@H:26]([O:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[C:35]1[CH:40]=[CH:39][C:38]([C:41]([N:43]2[CH2:48][CH2:47][CH:46]([N:49]3[C:58]4[C:53](=[N:54][CH:55]=[C:56]([Cl:59])[CH:57]=4)[CH2:52][C:51]([CH3:61])([CH3:60])[C:50]3=[O:62])[CH2:45][CH2:44]2)=[O:42])=[C:37]([F:63])[CH:36]=1)[CH3:27])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(OCC)(=O)C>[Cl:59][C:56]1[CH:57]=[C:58]2[C:53]([CH2:52][C:51]([CH3:60])([CH3:61])[C:50](=[O:62])[N:49]2[CH:46]2[CH2:45][CH2:44][N:43]([C:41]([C:38]3[CH:39]=[CH:40][C:35]([C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=4[O:28][C@H:26]([CH3:27])[CH2:25][CH2:24][OH:23])=[CH:36][C:37]=3[F:63])=[O:42])[CH2:48][CH2:47]2)=[N:54][CH:55]=1

Komponenten

5

Edukt 3

HCID 8028Tetrahydrofuran2×HCID 2724141Tetrabutylammonium FluorideHCID 680062751-{1-[(2'-{[(1R)-3-{[tert-butyl(diphenyl)silyl]oxy}-1-methylpropyl]oxy}-3-fluorobiphenyl-4-yl)carbonyl]piperidin-4-yl}-7-chloro-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-one

Produkt 1

HCID 683151677-chloro-1-{1-[(3-fluoro-2'-{[(1R)-3-hydroxy-1-methylpropyl]oxy}biphenyl-4-yl)carbonyl]piperidin-4-yl}-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-oneAusbeute 80,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a tetrahydrofuran solution (11 ml) of 1-{1-[(2′-{[(1R)-3-{[tert-butyl(diphenyl)silyl]oxy}-1-methylpropyl]oxy}-3-fluorobiphenyl-4-yl)carbonyl]piperidin-4-yl}-7-chloro-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-one (525 mg) was added at room temperature a tetrahydrofuran solution (1 M, 1.28 ml) of tetrabutylammonium fluoride, followed by stirring for 3 hours. The reaction solution was diluted with ethyl acetate, washed sequentially with a saturated aqueous ammonium chloride solution and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to afford 7-chloro-1-{1-[(3-fluoro-2′-{[(1R)-3-hydroxy-1-methylpropyl]oxy}biphenyl-4-yl)carbonyl]piperidin-4-yl}-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-one (301 mg).

Aufarbeitung

  1. washwashed sequentially with a saturated aqueous ammonium chloride solution and saturated sodium chloride solution
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting residue was purified by silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-51f2b013f8044678a597a206eeff365e
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08729095B2

Notizen zur Reaktion

Wird geladen…