Potassium Carbonate → Abt-288

HRID 912486

Reaction equation

HRID 912486 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][CH2:17][C@@H:16]4[CH2:19][N:20]([CH3:22])[CH2:21][C@H:15]34)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[N:23]1[NH:24][C:25](=[O:29])[CH:26]=[CH:27][CH:28]=1.C(=O)([O-])[O-].[K+].[K+]>N1C2C(=CC=CC=2)C=CC=1.CCCCCC.[Cu]>[CH3:22][N:20]1[CH2:19][C@@H:16]2[C@@H:15]([N:14]([C:11]3[CH:12]=[CH:13][C:8]([C:5]4[CH:6]=[CH:7][C:2]([N:24]5[C:25](=[O:29])[CH:26]=[CH:27][CH:28]=[N:23]5)=[CH:3][CH:4]=4)=[CH:9][CH:10]=3)[CH2:18][CH2:17]2)[CH2:21]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 681533(2H)-PyridazinoneHCID 44221914(3aR,6aR)-1-(4'-bromo-biphenyl-4-yl)-5-methyl-octahydro-pyrrolo[3,4-b]pyrrole

Product 1

HCID 24743471Abt-288

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 7047QuinolineSolventHCID 8058HexaneSolvent

Conditions

Temperature
150 °C

Procedure

The product of Example 1A (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 a CELITE filter (CELITE is a registered trademark of Johns-Manville Corporation of Denver, Colo.). 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% MeOH in dichloromethane) to provide the title compound, 2-{4′-[(3aR,6aR)-5-methylhexahydropyrrolo [3,4-b]pyrrol-1(2H)-yl]-1,1′-biphenyl-4-yl}pyridazin-3(2H)-one. 1H NMR (300 MHz, CDCl3) δ ppm 7.91 (dd, J=3.73, 1.70 Hz, 1 H) 7.61-7.65 (m, 4 H) 7.51 (d, J=8.48 Hz, 2 H) 7.25 (dd, dd, J=9.40, 4.07 Hz, 1 H) 7.07 (dd, J=9.49, 1.70 Hz, 1 H) 6.64 (d, J=8.81 Hz, 2 H) 4.19-4.27 (m, 1 H) 3.54-3.64 (m, 1 H) 3.28-3.38 (m, 1 H) 3.00-3.11 (m, 1 H) 2.56-2.85 (m, 4 H) 2.40 (s, 3 H) 2.10-2.29 (m, 1 H) 1.89-2.05 (m, J=6.78 Hz, 1 H); 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.).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. filtrationfiltered through a CELITE
  3. filtrationfilter (CELITE
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customthe residue was purified by chromatography (
  6. washeluting first with diethyl ether
  7. washelution
  8. additionwith a mixture of 5% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-6d43f6e1719241999aeb4d8934e0346b
Source dataset
uspto-grants-2011_09
Patent number
US08026240B2

Linked notes

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