2-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl → N-(4-(3-(2-(methylamino)pyridin-4-yl)pyridin-2-yloxy)phenyl)-4-phenyl-6,7-dihydro-5H-cyclopenta[d]pyridazin-1-amine

HRID 227780Notes

Reaction equation

HRID 227780 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[NH2:30][C:31]1[CH:51]=[CH:50][C:34]([O:35][C:36]2[C:41]([C:42]3[CH:47]=[CH:46][N:45]=[C:44]([NH:48][CH3:49])[CH:43]=3)=[CH:40][CH:39]=[CH:38][N:37]=2)=[CH:33][CH:32]=1.Cl[C:53]1[C:58]2[CH2:59][CH2:60][CH2:61][C:57]=2[C:56]([C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)=[N:55][N:54]=1.CC(C)([O-])C.[Na+]>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]>[CH3:49][NH:48][C:44]1[CH:43]=[C:42]([C:41]2[C:36]([O:35][C:34]3[CH:50]=[CH:51][C:31]([NH:30][C:53]4[N:54]=[N:55][C:56]([C:62]5[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=5)=[C:57]5[CH2:61][CH2:60][CH2:59][C:58]=45)=[CH:32][CH:33]=3)=[N:37][CH:38]=[CH:39][CH:40]=2)[CH:47]=[CH:46][N:45]=1

Participants

6

Reactant 4

HCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 23676156Sodium t-butoxideHCID 667351614-(2-(4-aminophenoxy)pyridin-3-yl)-N-methylpyridin-2-amineHCID 866141641-Chloro-6,7-dihydro-4-phenyl-5H-cyclopenta[d]pyridazine

Product 1

HCID 57756249N-(4-(3-(2-(methylamino)pyridin-4-yl)pyridin-2-yloxy)phenyl)-4-phenyl-6,7-dihydro-5H-cyclopenta[d]pyridazin-1-amine

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

A resealable reaction tube was charged with tris(dibenzylideneacetone)dipalladium (0) (0.012 g, 0.013 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (0.021 g, 0.051 mmol), 4-(2-(4-aminophenoxy)pyridin-3-yl)-N-methylpyridin-2-amine (0.075 g, 0.257 mmol), 1-chloro-4-phenyl-6,7-dihydro-5H-cyclopenta[d]pyridazine (0.059 g, 0.257 mmol), and sodium tert-butoxide (0.035 g, 0.359 mmol). This mixture was purged with nitrogen for several minutes, followed by addition of 0.780 mL of toluene. The vial was capped and heated at 100° C. for 1.5 h. Upon cooling, ethyl acetate was added and a precipitate formed. After filtration and washing with EtOAc, the crude material was purified by ISCO silica gel chromatography (90/10/1 DCM/MeOH/NH4OH, 12 g column), to provide N-(4-(3-(2-(methylamino)pyridin-4-yl)pyridin-2-yloxy)phenyl)-4-phenyl-6,7-dihydro-5H-cyclopenta[d]pyridazin-1-amine as a tan solid. MS m/z=487 [M+H]+. Calc'd for C30H26N6O: 486.57.

Workup

  1. customThis mixture was purged with nitrogen for several minutes
  2. additionfollowed by addition of 0.780 mL of toluene
  3. customThe vial was capped
  4. temperatureUpon cooling
  5. additionethyl acetate was added
  6. customa precipitate formed
  7. filtrationAfter filtration
  8. washwashing with EtOAc
  9. customthe crude material was purified by ISCO silica gel chromatography (90/10/1 DCM/MeOH/NH4OH, 12 g column)

Sources & evidence

ORD record
ord-acd29f831caa4816ad8ba446f1710e4f
Source dataset
uspto-grants-2009_07
Patent number
US07560551B2

Reaction notes

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