4-Aminopyridine → HCID 45266972, compound

HRID 272684Notes

Reaction equation

HRID 272684 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[C:11](=[O:12])[NH:10][C:9]3[CH:13]=[C:14]([C:17]([OH:20])([CH3:19])[CH3:18])[CH:15]=[CH:16][C:8]=3[NH:7][C:6]=2[CH:21]=1.[NH2:22][C:23]1[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=1.C([O-])([O-])=O.[Cs+].[Cs+]>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]>[OH:20][C:17]([C:14]1[CH:15]=[CH:16][C:8]2[NH:7][C:6]3[CH:21]=[C:2]([NH:22][C:23]4[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=4)[CH:3]=[CH:4][C:5]=3[C:11](=[O:12])[NH:10][C:9]=2[CH:13]=1)([CH3:19])[CH3:18]

Participants

6

Reactant 3

HCID 17274-AminopyridineHCID 10796Cesium carbonateHCID 69219260HCID 69219260, compound

Product 1

HCID 45266972HCID 45266972, compoundYield 75%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of Example 189A (60 mg, 0.20 mmol), 4-aminopyridine (26 mg, 0.24 mmol), Pd2 (dba)3 (9.2 mg, 0.01 mmol), CyMAP (11.8 mg, 0.03 mmol), and Cs2CO3 (78 mg, 0.24 mmol) in 2 mL of dioxane was heated at 85° C. overnight. After the reaction mixture cooled to room temperature, it was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc three times. The combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel with 100:5:1 EtOAc/MeOH/NH4OH to provide 54 mg (75%) of the desired product. MS (DCI) m/e 361 (M+H)+; 1H NMR (500 MHz, DMSO-d6) δ 9.49 (s, 1H), 9.01 (s, 1H), 8.29 (d, J=4.68 Hz, 1H), 7.79 (s, 1H), 7.64 (d, J=8.73 Hz, 1H), 7.09 (d, J=1.87 Hz, 1H), 6.99-7.03 (m, 3H), 6.86-6.89 (m, 2H), 6.63 (dd, J=8.58, 2.03 Hz, 1H), 4.68 (s, 1H), 1.36 (m, 6H).

Workup

  1. customit was partitioned between EtOAc and water
  2. extractionThe aqueous layer was extracted with EtOAc three times
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by flash column chromatography on silica gel with 100:5:1 EtOAc/MeOH/NH4OH

Sources & evidence

ORD record
ord-9a14067ff32248759a7ce694d4b8d5bb
Source dataset
uspto-grants-2008_11
Patent number
US07456169B2

Reaction notes

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