2-Aminopyridine → 3-[3-(2-Chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzonitrile

HRID 419308ノート

反応式

HRID 419308 の反応式
[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][C:9]([C:11]2[CH:12]=[C:13]([CH:16]=[CH:17][CH:18]=2)[C:14]#[N:15])=O)[CH:5]=[CH:4][N:3]=1.Cl[C:20]1[N:25]=[C:24](/[CH:26]=[C:27](\[C:29]2C=C(C=CC=2)C#N)/O)C=C[N:21]=1.C1C(=O)N(Br)C(=O)C1.NC1C=CC=CN=1>C(Cl)Cl.CCOC(C)=O.O>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[N:25]3[CH:24]=[CH:26][CH:27]=[CH:29][C:20]3=[N:21][C:9]=2[C:11]2[CH:12]=[C:13]([CH:16]=[CH:17][CH:18]=2)[C:14]#[N:15])[CH:5]=[CH:4][N:3]=1

参加物

8

反応物 4

HCID 104392-AminopyridineHCID 67184N-bromobutanimideHCID 866251883-[(2-Chloro-4-pyrimidinyl)acetyl]benzonitrileHCID 1363426543-[(E)-2-(2-chloro-4-pyrimidinyl)-1-hydroxyethenyl]benzonitrile

生成物 1

HCID 866251873-[3-(2-Chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzonitrile収率 75%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

A mixture of tautomers, 3-[(2-chloro-4-pyrimidinyl)acetyl]benzonitrile and 3-[(E)-2-(2-chloro-4-pyrimidinyl)-1-hydroxyethenyl]benzonitrile, (1.56 g, 6.05 mmol) was dissolved in 100 mL of DCM with stirring and cooled to 0° C. NBS (1.08 g, 6.07 mmol) was added and the reaction was allowed to warm to rt. The reaction was stirred for one hour and concentrated in vacuo. The residue was dissolved in dioxane with stirring. 2-Aminopyridine (1.71 g, 18.2 mmol) was added, and the reaction was heated to 60° C. The reaction was stirred overnight and cooled to rt. The reaction was poured into H2O and EtOAc. The layers were separated, and the organic layer was washed with brine. The combined aqueous layers were extracted with DCM (2×) and EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography, and fractions containing product were concentrated in vacuo. The residue was triturated with diethyl ether and hexanes (˜1:1), filtered, and the solid was washed with diethyl ether and hexanes (˜1:1). The solid was collected to provide 1.50 g (75%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 9.35 (d, J=7.0 Hz, 1H), 8.60 (d, J=5.3 Hz, 1H), 8.14 (s, 1H), 7.98 (d, J=7.9 Hz, 1H), 7.93 (d, J=7.9 Hz, 1H), 7.81 (d, J=8.8 Hz, 1H), 7.67 (t, J=7.9 Hz, 1H), 7.59 (dd, J=6.8, 1.1 Hz, 1H), 7.31-7.17 (m, 2H).

後処理

  1. temperatureto warm to rt
  2. stirringThe reaction was stirred for one hour
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in dioxane
  5. stirringwith stirring
  6. temperaturethe reaction was heated to 60° C
  7. stirringThe reaction was stirred overnight
  8. temperaturecooled to rt
  9. customThe layers were separated
  10. washthe organic layer was washed with brine
  11. extractionThe combined aqueous layers were extracted with DCM (2×) and EtOAc
  12. dry with materialThe combined organic layers were dried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customThe residue was purified by flash chromatography, and fractions
  16. additioncontaining product
  17. concentrationwere concentrated in vacuo
  18. customThe residue was triturated with diethyl ether and hexanes (˜1:1)
  19. filtrationfiltered
  20. washthe solid was washed with diethyl ether and hexanes (˜1:1)
  21. customThe solid was collected

出典と根拠

ORDレコード
ord-d5647bd9c987406fab60059a150f7cc4
出典データセット
uspto-grants-2012_01
特許番号
US08093239B2

反応ノート

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