4-Aminopyridine → HCID 59023800, compound

HRID 1678228Notes

Reaction equation

HRID 1678228 reaction equation
[C:1]1([NH:7][C:8]([C:10]2[C:18]3[C:14](=[CH:15][N:16](CC4C=CC(OC)=CC=4)[N:17]=3)[CH:13]=[C:12](Br)[CH:11]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:29][C:30]1[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([SiH](C(C)C)C(C)C)(C)C>O1CCOCC1.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]>[C:1]1([NH:7][C:8]([C:10]2[CH:11]=[C:12]([NH:29][C:30]3[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=3)[CH:13]=[C:14]3[C:18]=2[NH:17][N:16]=[CH:15]3)=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

8

Reactant 5

HCID 17274-AminopyridineHCID 10796Cesium carbonateHCID 138754Silane, tris(1-methylethyl)-HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59024300HCID 59024300, compound

Product 1

HCID 59023800HCID 59023800, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 5-bromo-2-(4-methoxy-benzyl)-2H-indazole-7-carboxylic acid, phenylamide (prepared from preparation #12a using general procedures V and B, 75.0 mg, 0.20 mmol), 4-aminopyridine(24.0 mg, 0.25 mmol), cesium carbonate (195 mg, 0.60 mmol), and XANTPHOS (11.6 mg, 0.02 mmol) was suspended in 1,4-dioxane (2.5 mL) at ambient temperature under an inert atmosphere. Tris(dibenzylideneacetone)dipalladium(0) (9.2 mg, 0.01 mmol) was added and nitrogen gas was bubbled through the resulting suspension for about 5 minutes. The reaction mixture was heated at about 95° C. for about 2 hours. The resulting mixture was allowed to cool to ambient temperature and filtered through a celite pad and the solvent was removed under reduced pressure. The residue was dissolved in trifluoroacetic acid (4.0 mL) containing triisopropylsilane (51.0 uL, 0.25 mmol) and the mixture was heated at about 100° C. in a microwave reactor for about 15 minutes. Solvents were removed under reduced pressure and the residue was purified preparative RP-HPLC (Rainin C18, 8 mm, 300 Å, 35 cm; 5-100% acetonitrile/0.1 M ammonium acetate over 20 min, 100% acetonitrile hold 10 minutes, 21 mL/min) to afford N-phenyl-5-(pyridin-4-ylamino)-1H-indazole-7-carboxamide (30 mg, 46%) as an off-white solid, RP HPLC (Table 1, Method e) Rt=1.32; MS m/z: (MH)+ 330.

Workup

  1. customnitrogen gas was bubbled through the resulting suspension for about 5 minutes
  2. temperatureto cool to ambient temperature
  3. filtrationfiltered through a celite pad
  4. customthe solvent was removed under reduced pressure
  5. dissolutionThe residue was dissolved in trifluoroacetic acid (4.0 mL)
  6. temperaturethe mixture was heated at about 100° C. in a microwave reactor for about 15 minutes
  7. customSolvents were removed under reduced pressure
  8. customthe residue was purified preparative RP-HPLC (Rainin C18, 8 mm, 300 Å, 35 cm; 5-100% acetonitrile/0.1 M ammonium acetate over 20 min, 100% acetonitrile hold 10 minutes, 21 mL/min)

Sources & evidence

ORD record
ord-4fec239568444c1587e70e8200dce1f4
Source dataset
uspto-grants-2011_08
Patent number
US08008481B2

Reaction notes

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