Trimethylsilylacetylene → 6'-((Trimethylsilyl)ethynyl)-2-fluoro-5-(4-piperidin-1-ylmethyl-phenyl)-[3,4']bipyridinyl-3'-ylamine

HRID 1506067ノート

反応式

HRID 1506067 の反応式
Br[C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:9]2[C:10]([F:28])=[N:11][CH:12]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][N:22]4[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]4)=[CH:17][CH:16]=3)[CH:14]=2)[CH:3]=1.C(N(CC)C(C)C)(C)C.[CH3:38][Si:39]([C:42]#[CH:43])([CH3:41])[CH3:40]>O1CCOCC1.C(Cl)Cl.CO.[Cu]I.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>[CH3:38][Si:39]([C:42]#[C:43][C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:9]2[C:10]([F:28])=[N:11][CH:12]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][N:22]4[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]4)=[CH:17][CH:16]=3)[CH:14]=2)[CH:3]=1)([CH3:41])[CH3:40]

参加物

9

反応物 3

HCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 582666266'-Bromo-2-fluoro-5-(4-piperidin-1-ylmethylphenyl)-[3,4]bipyridinyl-3'-ylamine

生成物 1

HCID 582665496'-((Trimethylsilyl)ethynyl)-2-fluoro-5-(4-piperidin-1-ylmethyl-phenyl)-[3,4']bipyridinyl-3'-ylamine

試薬・触媒・溶媒 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418397HCID 178418397、化合物触媒HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A mixture of 6′-bromo-2-fluoro-5-(4-piperidin-1-ylmethylphenyl)-[3,4′]bipyridinyl-3′-ylamine (100 mg, 0.23 mmol), copper (I) iodide (4.3 mg, 0.02 mmol), and N,N-diisopropylethylamine (0.08 mL, 0.45 mmol) in anhydrous 1,4-dioxane (2.5 mL) was degassed and flushed with nitrogen. Tetrakis(triphenylphosphine)palladium(0) (26 mg, 0.02 mmol) and (trimethylsilyl)acetylene (0.16 mL, 1:1 mmol) were added and the reaction was heated at 100° C. for 5 h. The cooled reaction mixture was diluted with DCM (20 mL) and methanol (2 mL) and washed with water (15 mL). The organic phase was separated, dried over sodium sulfate, filtered and evaporated in vacuo to afford a residue that was purified by flash chromotagraphy (silica, 10 g column, Biotage, 0-10% methanol in (DCM containing 1% 7M ammonia in ammonia)) to afford a brown residue that was taken to the next step without further purification.

後処理

  1. customwas degassed
  2. customflushed with nitrogen
  3. customThe cooled reaction mixture
  4. washwashed with water (15 mL)
  5. customThe organic phase was separated
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customto afford a residue that
  10. customwas purified by flash chromotagraphy (silica, 10 g column, Biotage, 0-10% methanol in (DCM containing 1% 7M ammonia in ammonia))
  11. customto afford a brown residue that
  12. customwas taken to the next step without further purification

出典と根拠

ORDレコード
ord-d7330a0eefc74e8fb8431e616e218e49
出典データセット
uspto-grants-2015_12
特許番号
US09216980B2

反応ノート

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