2-Aminopyridine → HCID 178461249, compound

HRID 1852804Notes

Reaction equation

HRID 1852804 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][N:30]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[K+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[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][N: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 4

HCID 104392-AminopyridineHCID 634876Binap, (A+-)-HCID 23665647Potassium tert-butoxideHCID 178461197HCID 178461197, compound

Product 1

HCID 178461249HCID 178461249, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

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) (0.5 g, 1.128 mmol) in toluene (5 mL) in a pyrex tube, 2-aminopyridine (0.127 g, 1.35 mmol), and BINAP (35 mg, 0.056 mmol) were added, and the reaction mixture was degassed with argon for 5 minutes. Pd2(dba)3 (51 mg, 0.056 mmol) and potassium tert-butoxide (0.189 g, 1.69 mmol) were added, and the tube was capped and heated to 100° C. for 17 h. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure, The residue was dissolved in ethyl acetate (20 mL), washed with water (5 mL) and brine (5 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified on a silica gel column using 40% ethyl acetate/petroleum ether as eluent to give 4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-(pyridin-2-ylamino)-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ES/APCI calc'd. for C25H24ClN7 [M+H]+ 458. found 458.

Workup

  1. customthe reaction mixture was degassed with argon for 5 minutes
  2. customthe tube was capped
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customthe solvent was removed under reduced pressure
  5. dissolutionThe residue was dissolved in ethyl acetate (20 mL)
  6. washwashed with water (5 mL) and brine (5 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified on a silica gel column

Sources & evidence

ORD record
ord-11880a42013041df8061b33acc1e9a60
Source dataset
uspto-grants-2015_02
Patent number
US08962611B2

Reaction notes

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