Potassium Hydroxide → 2-(4'-((3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-1(2H)-yl)biphenyl-4-yl)pyridazin-3(2H)-one

HRID 12981

Reaktionsgleichung

Reaktionsgleichung von HRID 12981
[O:1]=[C:2]1[N:7]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:19]=[CH:18][C:17]([N:20]4[CH2:24][CH2:23][C@@H:22]5[CH2:25][N:26](C(OCC)=O)[CH2:27][C@H:21]45)=[CH:16][CH:15]=3)=[CH:10][CH:9]=2)[N:6]=[CH:5][CH:4]=[CH:3]1.[OH-].[K+]>CC(O)=O.Cl.O>[N:20]1([C:17]2[CH:18]=[CH:19][C:14]([C:11]3[CH:12]=[CH:13][C:8]([N:7]4[C:2](=[O:1])[CH:3]=[CH:4][CH:5]=[N:6]4)=[CH:9][CH:10]=3)=[CH:15][CH:16]=2)[CH2:24][CH2:23][C@@H:22]2[CH2:25][NH:26][CH2:27][C@H:21]12

Komponenten

6

Edukt 2

HCID 14797Potassium HydroxideHCID 67396526(3aR,6aR)-ethyl 1-(4'-(6-oxopyridazin-1(6H)-yl)biphenyl-4-yl)hexahydropyrrolo[3,4-b]pyrrole-5(1H)-carboxylate

Produkt 1

HCID 673963272-(4'-((3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-1(2H)-yl)biphenyl-4-yl)pyridazin-3(2H)-one

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 176Acetic AcidLösungsmittelHCID 313Hydrochloric AcidLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

The product from Example 85A (0.110 g, 0.256 mmol) was dissolved in 3 mL of a 1:1 mixture of HOAc and 12 M aqueous HCl, and heated at 100° C. for 16 hours in a sealed vessel. The mixture was cooled to 0° C., diluted with 15 mL of water, and the pH was adjusted to ˜10 by the dropwise addition of 20% (w/v) aqueous KOH. The mixture was extracted three times with 25 mL of 5% n-propanol in CHCl3 and the combined extracts were dried over Na2SO4, filtered, and absorbed on silica gel. The crude material was chromatographed, eluting with 0-5% aqueous NH4OH in MeCN/MeOH (9:1), to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.91 (dd, J=3.7, 1.7 Hz, 1H), 7.64 (s, 4H), 7.52 (d, J=8.8 Hz, 2H), 7.21-7.27 (m, 1H), 7.07 (dd, J=9.5, 1.7 Hz, 1H), 6.65 (d, J=8.8 Hz, 2H), 4.10-4.19 (m, 1H), 3.56-3.67 (m, 1H), 3.23-3.35 (m, 1H), 2.91-3.22 (m, 5H), 2.15-2.32 (m, 1H), 2.12 (br s, 1H), 1.87 (ddd, J=12.9, 7.5 Hz, 1H), MS (ESI+) m/z 359 (M+H)+.

Aufarbeitung

  1. temperatureThe mixture was cooled to 0° C.
  2. extractionThe mixture was extracted three times with 25 mL of 5% n-propanol in CHCl3
  3. dry with materialthe combined extracts were dried over Na2SO4
  4. filtrationfiltered
  5. customabsorbed on silica gel
  6. customThe crude material was chromatographed
  7. washeluting with 0-5% aqueous NH4OH in MeCN/MeOH (9:1)

Quellen und Nachweise

ORD-Eintrag
ord-f0ccb16eb8f5487bb11ef0f6794277b9
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07728031B2

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