Cesium fluoride → tert-Butyl (1S,3R)-3-(6-(5-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yloxy)cyclohexylcarbamate

HRID 1775104ノート

反応式

HRID 1775104 の反応式
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[C:9]3[C:15]([Sn](C)(C)C)=[N:14][N:13]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:10]3=[CH:11][N:12]=2)[CH:2]=1.Br[C:29]1[N:34]=[C:33]([O:35][C@@H:36]2[CH2:41][CH2:40][CH2:39][C@H:38]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])[CH2:37]2)[CH:32]=[CH:31][CH:30]=1.[F-].[Cs+]>CN(C)C=O.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[C:9]3[C:15]([C:29]4[N:34]=[C:33]([O:35][C@@H:36]5[CH2:41][CH2:40][CH2:39][C@H:38]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:47])([CH3:46])[CH3:48])[CH2:37]5)[CH:32]=[CH:31][CH:30]=4)=[N:14][N:13]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:10]3=[CH:11][N:12]=2)[CH:2]=1

参加物

8

反応物 3

HCID 25953Cesium fluorideHCID 71253848HCID 71253848、化合物HCID 86676699tert-Butyl (1S,3R)-3-(6-bromopyridin-2-yloxy)cyclohexylcarbamate

生成物 1

HCID 86676700tert-Butyl (1S,3R)-3-(6-(5-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yloxy)cyclohexylcarbamate収率 53%

試薬・触媒・溶媒 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
50 °C

実験手順

A mixture of 147 mg (0.3 mmol) of 5-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-3-(trimethylstannyl)-1H-pyrazolo[3,4-c]pyridine, 123 mg, 0.33 mmol) of tert-butyl (1S,3R)-3-(6-bromopyridin-2-yloxy)cyclohexylcarbamate, 109 mg (0.72 mmol) of Cesium fluoride, 35 mg (0.03 mmol) of tetrakis(triphenylphosphine)palladium(0) and 11.4 mg (0.06 mmol) of copper(I) iodide in 2 ml of N,N-dimethylformamide was heated at 50° C. for 2 hours in a Stille coupling. The mixture was diluted with water and extracted with ethyl acetate. The organic extracts were washed with water, brine, dried over MgSO4 and concentrated. The residue was purified via silica gel chromatography using a gradient of ethyl acetate in heptane to afford 98 mg (53%) of tert-Butyl (1S,3R)-3-(6-(5-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yloxy)cyclohexylcarbamate. ESI MS m/z 617.5 (M+1).

後処理

  1. extractionextracted with ethyl acetate
  2. washThe organic extracts were washed with water, brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified via silica gel chromatography

出典と根拠

ORDレコード
ord-cd387be5ea374d3e819c28f026b2e1d8
出典データセット
uspto-grants-2016_02
特許番号
US09260425B2

反応ノート

読み込み中…