Reaktion #41232

Reaktionsgleichung

product

(3aR,6aR)-1-(4′-Bromo-biphenyl-4-yl)-5-methyl-octahydro-pyrrolo[3,4-b]pyrrole

3(2H)-pyridazinone

potassium carbonate

→

title compound

2-{4′-[(3aR,6aR)-5-methylhexahydropyrrolo[3,4-b]pyrrol-1(2H)-yl]-1,1′-biphenyl-4-yl}pyridazin-3(2H)-one

Lösungsmittel

quinoline

hexane

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe mixture was cooled to room temperature
2. 2
   Filtrationfiltered through CELITE®
3. 3
   EinengenThe filtrate was concentrated under reduced pressure
4. 4
   Sonstigethe residue was purified by chromatography (
5. 5
   Wascheneluting first with diethyl ether
6. 6
   Waschenelution
7. 7
   workup.ADDITIONwith a mixture of 5% methanol in dichloromethane)

Vorschrift

The product of Example 41A (4.54 g, 12.6 mmole), 3(2H)-pyridazinone (2.41 g, 25.2 mmole), copper powder (1.60 g, 25.2 mmole) and potassium carbonate (5.21 g, 37.7 mmole) were dissolved in 63 ml of quinoline and heated at 150° C. under N2 for 48 hours. The mixture was cooled to room temperature, diluted with hexane (15 ml) and filtered through CELITE®. The filtrate was concentrated under reduced pressure and the residue was purified by chromatography (eluting first with diethyl ether, followed by dichloromethane, then elution with a mixture of 5% methanol in dichloromethane) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.91 (dd, J=3.73, 1.70 Hz, 1H) 7.61-7.65 (m, 4H) 7.51(d, J=8.48 Hz, 2H) 7.25 (dd, dd, J=9.40, 4.07 Hz, 1H) 7.07 (dd, J=9.49, 1.70 Hz, 1H) 6.64 (d, J=8.81 Hz, 2H) 4.19-4.27 (m, 1H) 3.54-3.64 (m, 1H) 3.28-3.38 (m, 1H) 3.00-3.11 (m, 1H) 2.56-2.85 (m, 4H) 2.40 (s, 3H) 2.10-2.29 (m, 1H) 1.89-2.05 (m, J=6.78 Hz, 1H); MS (M+H)+=373. The solid (3aR,6aR)-2-[4′-(5-methyl-hexahydro-pyrrolo[3,4-b]pyrrol-1-yl)-biphenyl-4-yl]-2H-pyridazin-3-one obtained showed a melting range of 204-207° C. (dec.). To a solution of (3aR,6aR)-2-[4′-(5-methyl-hexahydro-pyrrolo[3,4-b]pyrrol-1-yl)-biphenyl-4-yl]-2H-pyridazin-3-one in methanol was added D-(−)-tartaric acid; a solid formed which was collected by filtration and dried to give a solid of m.p. 218-221° C. In like manner, a methanolic solution of (3aR,6aR)-2-[4′-(5-methyl-hexahydro-pyrrolo[3,4-b]pyrrol-1-yl)-biphenyl-4-yl]-2H-pyridazin-3-when treated with L-(+)-tartaric acid, followed by concentration of the solution and addition of diethyl ether, gave a solid of map 206-209° C. A methanolic solution of (3aR,6aR)-2-[4′-(5-methyl-hexahydro-pyrrolo[3,4-b]pyrrol-1-yl)-biphenyl-4-yl]-2H-pyridazin-3—when treated with phosphoric acid, followed by concentration of the solution, gave a solid of m.p. 224-229° C. A methanolic solution of (3aR,6aR)-2-[4′-(5-methyl-hexahydro-pyrrolo[3,4-b]pyrrol-1-yl)-biphenyl-4-yl]-2H-pyridazin-3—when treated with salicylic acid, followed by concentration of the solution and addition of diethyl ether and hexane, gave a solid of m p. 115-118° C. A methanolic solution of (3aR,6aR)-2-[4′-(5-methyl-hexahydro-pyrrolo[3,4-b]pyrrol-1-yl)-biphenyl-4-yl]-2H-pyridazin-3—when treated with ascorbic acid, followed by concentration of the solution and addition of diethyl ether and hexane, gave a solid of m.p. 163-167° C. A methanolic solution of (3aR,6aR)-2-[4′-(5-methyl-hexahydro-pyrrolo[3,4-b]pyrrol-1-yl)-biphenyl-4-yl]-2H-pyridazin-3—when treated with sulfuric acid, followed by concentration of the solution and addition of diethyl ether, gave a solid of m.p. 232-235° C.

Quelle