Aniline → HCID 178461248, compound

HRID 81197Notes

Reaction equation

HRID 81197 reaction equation
Br[C:2]1[N:19]([CH2:20][C@H:21]2[CH2:26][CH2:25][C@H:24]([CH3:27])[CH2:23][CH2:22]2)[C:5]2[C:6]([C:12]3[CH:13]=[N:14][CH:15]=[C:16]([Cl:18])[CH:17]=3)=[N:7][C:8]([C:10]#[N:11])=[CH:9][C:4]=2[N:3]=1.[NH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1COCC1.CC(C1C=C(C(C)C)C(C2C(OC)=CC(Cl)=C(OC)C=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.[Pd+2]>[Cl:18][C:16]1[CH:17]=[C:12]([C:6]2[C:5]3[N:19]([CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([CH3:27])[CH2:23][CH2:22]4)[C:2]([NH:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[N:3][C:4]=3[CH:9]=[C:8]([C:10]#[N:11])[N:7]=2)[CH:13]=[N:14][CH:15]=1

Participants

7

Reactant 3

HCID 6115AnilineHCID 23676156Sodium t-butoxideHCID 178461197HCID 178461197, compound

Product 1

HCID 178461248HCID 178461248, compound

Reagents, catalysts & solvents 3

HCID 75412134Dicyclohexyl(2 inverted exclamation mark,4 inverted exclamation mark,6 inverted exclamation mark-Triisopropyl-3,6-Dimethoxy-[1,1 inverted exclamation mark-Biphenyl]-2-Yl)Phosphine-(2-(2-Aminoethyl)Phenyl)Palladium(Ii) ChlorideCatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-bromo-4-(5-chloropyridin-3-yl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Preparative Example 3.1, 500 mg, 1.35 mmol) in toluene (5 mL), was added aniline (0.13 mL, 1.48 mmol) and chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(II) (BrettPhos precatalyst, 107 mg, 0.135 mmol), and the reaction was deoxygenated by purging with nitrogen for 10 minutes. Sodium tert-butoxide (194 mg, 2.02 mmol) in THF (2 mL) was added, and the reaction was again purged with nitrogen for 5 minutes. The reaction flask was sealed, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with EtOAc (100 mL) and the layers were separated. The organic layer was washed with water (2×25 mL) followed by saturated brine solution (25 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated. The crude product was purified on a silica gel column (30% EtOAc/petroleum ether) to afford 4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-(phenylamino)-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ES/APCl calc'd. for C26H25ClN6 [M+H]+ 457. found 457.

Workup

  1. customthe reaction was deoxygenated
  2. customby purging with nitrogen for 10 minutes
  3. customthe reaction was again purged with nitrogen for 5 minutes
  4. customThe reaction flask was sealed
  5. additionThe reaction mixture was diluted with EtOAc (100 mL)
  6. customthe layers were separated
  7. washThe organic layer was washed with water (2×25 mL)
  8. dry with materialThe organic layer was dried over anhydrous Na2SO4
  9. concentrationconcentrated
  10. customThe crude product was purified on a silica gel column (30% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-e80ba561d51843019e5833f833e86497
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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