4-Aminopyridine → HCID 45266972, 화합물

HRID 272684노트

반응식

HRID 272684 반응식
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]

참가 물질

6

반응물 3

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

생성물 1

HCID 45266972HCID 45266972, 화합물수율 75%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-9a14067ff32248759a7ce694d4b8d5bb
출처 데이터셋
uspto-grants-2008_11
특허 번호
US07456169B2

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