4-Aminopyridine → HCID 45266972、化合物

HRID 272684ノート

反応式

HRID 272684 の反応式
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]

参加物

6

反応物 3

HCID 17274-AminopyridineHCID 10796Cesium carbonateHCID 69219260HCID 69219260、化合物

生成物 1

HCID 45266972HCID 45266972、化合物収率 75%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-9a14067ff32248759a7ce694d4b8d5bb
出典データセット
uspto-grants-2008_11
特許番号
US07456169B2

反応ノート

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