Sodium Hydroxide → 6-tert-Butyl-8-fluoro-2-{2-hydroxymethyl-3-[1-methyl-5-(1'-methyl-1',2',3',4',5',6'-hexahydro-[3,4]bipyridinyl-6-ylamino)-6-oxo-1,6-dihydro-pyridazin-3-yl]-phenyl}-2H-phthalazin-1-one

HRID 449709Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 449709
C([O:4][CH2:5][C:6]1[C:11]([C:12]2[CH:17]=[C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([CH:25]4[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]4)=[CH:21][N:20]=3)[C:15](=[O:32])[N:14]([CH3:33])[N:13]=2)=[CH:10][CH:9]=[CH:8][C:7]=1[N:34]1[N:43]=[CH:42][C:41]2[C:36](=[C:37]([F:48])[CH:38]=[C:39]([C:44]([CH3:47])([CH3:46])[CH3:45])[CH:40]=2)[C:35]1=[O:49])(=O)C.[OH-].[Na+]>C1COCC1>[C:44]([C:39]1[CH:40]=[C:41]2[C:36](=[C:37]([F:48])[CH:38]=1)[C:35](=[O:49])[N:34]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]([C:12]3[CH:17]=[C:16]([NH:18][C:19]4[N:20]=[CH:21][C:22]([CH:25]5[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]5)=[CH:23][CH:24]=4)[C:15](=[O:32])[N:14]([CH3:33])[N:13]=3)[C:6]=1[CH2:5][OH:4])[N:43]=[CH:42]2)([CH3:47])([CH3:45])[CH3:46]

Komponenten

4

Edukt 2

HCID 14798Sodium Hydroxide2×HCID 667426042-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(1-methyl-5-(5-(1-methylpiperidin-4-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate

Produkt 1

HCID 566564516-tert-Butyl-8-fluoro-2-{2-hydroxymethyl-3-[1-methyl-5-(1'-methyl-1',2',3',4',5',6'-hexahydro-[3,4]bipyridinyl-6-ylamino)-6-oxo-1,6-dihydro-pyridazin-3-yl]-phenyl}-2H-phthalazin-1-oneAusbeute 84,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(1-methyl-5-(5-(1-methylpiperidin-4-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate (1.6 g) was dissolved in 20 mL THF. To the reaction solution was added 12 mL of 2 N NaOH. The reaction mixture was stirred at room temperature overnight. Reaction was not complete. An additional 10 equiv. of 2 N NaOH was added and the reaction mixture was stirred at room temperature for an additional 2 hours. THF was added until the reaction mixture was homogeneous and the reaction was heated to 40° C. for 30 min. The reaction was allowed to cool to room temperature and stirred overnight. The reaction had gone to completion as indicated by LC/MS. The reaction was concentrated to a reduced volume to remove most of the THF. A solid formed which was collected by filtration. The solid was redissolved in DCM, filtered through pack of celite, washed with water, dried over Na2SO4, filtered and conc in vacuo. to afford the desired product as a white solid (1.27 g). (M+H)+=624 m/e. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.45 (s, 9H) 1.80-1.92 (m, 5H) 2.31-2.58 (m, 3H) 3.03 (d, J=8.28 Hz, 1H) 3.92 (s and overlapping multiplet, 4H) 4.45 (d, J=6.53 Hz, 2H) 6.93 (d, J=8.28 Hz, 1H) 7.45-7.63 (m, 5H) 7.65-7.71 (m, 1H) 8.22-8.32 (m, 3H) 8.61 (s, 1H).

Aufarbeitung

  1. customReaction
  2. stirringthe reaction mixture was stirred at room temperature for an additional 2 hours
  3. temperaturethe reaction was heated to 40° C. for 30 min
  4. temperatureto cool to room temperature
  5. stirringstirred overnight
  6. concentrationThe reaction was concentrated to a reduced volume
  7. customto remove most of the THF
  8. customA solid formed which
  9. filtrationwas collected by filtration
  10. dissolutionThe solid was redissolved in DCM
  11. filtrationfiltered through pack of celite
  12. washwashed with water
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered and conc in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-521d0a2c45994aa190ac2400ae3cff88
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08481540B2

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