Cesium carbonate → 2-{4'-[(3aR,6aR)-5-Methylhexahydropyrrolo[3,4-b]pyrrol-1(2H)-yl]biphenyl-4-yl}-4,5-dihydropyridazin-3(2H)-one

HRID 12983

Reaction equation

HRID 12983 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[C:19](=[O:20])[CH2:18][CH2:17][CH:16]=[N:15]3)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.Cl.Cl.[CH3:23][N:24]1[CH2:31][C@@H:30]2[C@@H:26]([NH:27][CH2:28][CH2:29]2)[CH2:25]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>[O-]S(C(F)(F)F)(=O)=O.[Ag+].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[CH3:23][N:24]1[CH2:31][C@@H:30]2[C@@H:26]([N:27]([C:2]3[CH:7]=[CH:6][C:5]([C:8]4[CH:13]=[CH:12][C:11]([N:14]5[C:19](=[O:20])[CH2:18][CH2:17][CH:16]=[N:15]5)=[CH:10][CH:9]=4)=[CH:4][CH:3]=3)[CH2:28][CH2:29]2)[CH2:25]1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 684973422-(4'-bromobiphenyl-4-yl)-4,5-dihydropyridazin-3(2H)-oneHCID 68499270(3aR,6aR)-5-Methyloctahydropyrrolo[3,4-b]pyrrole dihydrochloride

Product 1

HCID 247438822-{4'-[(3aR,6aR)-5-Methylhexahydropyrrolo[3,4-b]pyrrol-1(2H)-yl]biphenyl-4-yl}-4,5-dihydropyridazin-3(2H)-oneYield 15.6%

Reagents, catalysts & solvents 3

HCID 76223Silver(I) trifluoromethanesulfonateCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A small pressure tube equipped with a magnetic stir bar was charged with 100 mg of 2-(4′-bromobiphenyl-4-yl)-4,5-dihydropyridazin-3(2H)-one, 58 mg of (3aR,6aR)-5-methylhexahydropyrrolo[3,4-b]pyrrole dihydrochloride, 350 mg of cesium carbonate, 15 mg of silver triflate, 4.2 mg of tris(dibenzylideneacetone)dipalladium, and 7.2 mg of 2-dicyclohexylphosphino-2′(N,N-dimethylamino)biphenyl and 2 ml of toluene. After sealing and purging with argon the tube was heated at 100° C. for 20 hours. Crude product was purified by flash chromatography (silica gel, gradient 2 to 10% methanol in dichloromethane), which yielded 17 mg of the title compound as a dark yellow oil. Mass spectroscopy gave (M+H)+ m/z 375.2, consistent with assigned structure.

Workup

  1. customA small pressure tube equipped with a magnetic stir bar
  2. custompurging with argon the tube
  3. customCrude product was purified by flash chromatography (silica gel, gradient 2 to 10% methanol in dichloromethane), which

Sources & evidence

ORD record
ord-d13f1c111a6a4d28ac8fdd786615866a
Source dataset
uspto-grants-2010_06
Patent number
US07728031B2

Linked notes

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