5-Chloro-3-ethynylpyridin-2-amine → 5-chloro-3-(5,6-dimethoxy-1-methyl-1H-indol-3-ylethynyl)pyridin-2-ylamine

HRID 2426843

反応式

HRID 2426843 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]#[CH:10])[C:5]([NH2:8])=[N:6][CH:7]=1.I[C:12]1[C:20]2[C:15](=[CH:16][C:17]([O:23][CH3:24])=[C:18]([O:21][CH3:22])[CH:19]=2)[N:14]([CH3:25])[CH:13]=1>C(N(CC)CC)C.CN(C)C=O.[Cu](I)I>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]#[C:10][C:12]2[C:20]3[C:15](=[CH:16][C:17]([O:23][CH3:24])=[C:18]([O:21][CH3:22])[CH:19]=3)[N:14]([CH3:25])[CH:13]=2)[C:5]([NH2:8])=[N:6][CH:7]=1

参加物

6

反応物 2

HCID 259186675-Chloro-3-ethynylpyridin-2-amineHCID 671474473-iodo-5,6-dimethoxy-1-methyl-1H-indole

生成物 1

HCID 671476445-chloro-3-(5,6-dimethoxy-1-methyl-1H-indol-3-ylethynyl)pyridin-2-ylamine収率 68%

試薬・触媒・溶媒 3

HCID 83717Copper iodide触媒HCID 6228Dimethylformamide溶媒HCID 8471Triethylamine溶媒

反応条件

温度
20 °C

実験手順

A suspension of 0.43 g of 5-chloro-3-ethynylpyridin-2-ylamine, 0.6 g of 3-iodo-5,6-dimethoxy-1-methyl-1H-indole (example 103-f), and 0.072 g of copper iodide, in a mixture of 60 ml of triethylamine and 30 ml of dimethylformamide, is degassed with argon for 15 minutes. 0.066 g of bis(triphenylphosphine)palladium(II) chloride is added to the above suspension. The mixture is agitated at around 20° C. for approximately 6 hours; 0.075 g of 5-chloro-3-ethynylpyridin-2-ylamine is added and the mixture is agitated at this same temperature for 2 days. The mixture is concentrated to dryness under reduced pressure (13 kPa). The residue is taken up with 100 ml of water and extracted with three times 100 ml of dichloromethane. The organic phases are combined, dried over magnesium sulfate, filtered, and concentrated under reduced pressure (13 kPa). The residue is purified by flash chromatography on a silica column [eluent: cyclohexane/ethyl acetate (50/50 by volume)]. 0.44 g of 5-chloro-3-(5,6-dimethoxy-1-methyl-1H-indol-3-ylethynyl)pyridin-2-ylamine is thus obtained in the form of a solid, the characteristics of which are as follows:

後処理

  1. customis degassed with argon for 15 minutes
  2. addition0.066 g of bis(triphenylphosphine)palladium(II) chloride is added to the above suspension
  3. addition0.075 g of 5-chloro-3-ethynylpyridin-2-ylamine is added
  4. stirringthe mixture is agitated at this same temperature for 2 days
  5. concentrationThe mixture is concentrated to dryness under reduced pressure (13 kPa)
  6. extractionextracted with three times 100 ml of dichloromethane
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure (13 kPa)
  10. customThe residue is purified by flash chromatography on a silica column [eluent: cyclohexane/ethyl acetate (50/50 by volume)]

出典と根拠

ORDレコード
ord-8d11c4b38ad044679f7f7e5d0de36d97
出典データセット
uspto-grants-2011_06
特許番号
US07968566B2

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