Water → 5-Trimethylsilylethynyl-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-aminopyridine

HRID 1845883ノート

反応式

HRID 1845883 の反応式
Br[C:2]1[CH:3]=[C:4]([O:9][CH2:10][C:11]2[C:16]([Cl:17])=[CH:15][CH:14]=[C:13]([F:18])[C:12]=2[Cl:19])[C:5]([NH2:8])=[N:6][CH:7]=1.[CH3:20][Si:21]([C:24]#[CH:25])([CH3:23])[CH3:22].[CH2:26](N(CC)CC)C.O>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:20][Si:21]([C:24]#[C:25][C:2]1[CH:3]=[C:4]([O:9][CH:10]([C:11]2[C:16]([Cl:17])=[CH:15][CH:14]=[C:13]([F:18])[C:12]=2[Cl:19])[CH3:26])[C:5]([NH2:8])=[N:6][CH:7]=1)([CH3:23])[CH3:22]

参加物

9

反応物 4

HCID 962WaterHCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 211114855-Bromo-3-(2,6-dichloro-3-fluoro-benzyloxy)-pyridin-2-ylamine

生成物 1

HCID 1234568855-Trimethylsilylethynyl-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-aminopyridine収率 62.9%

試薬・触媒・溶媒 4

HCID 11776Triphenylphosphine触媒HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

5-bromo-3-(2,6-dichloro-3-fluoro-benzyloxy)-pyridine-2-amine (3.8 g, 10 mmol), trimethylsilylethyne (3.87 mL, 28 mmol), triethylamine (Et3N, 4.15 mL, 30 mmol), triphenylphosphine (PPh3, 52 mg, 0.2 mmol) and bis(triphenylphosphine)palladium dichloride (PdCl2(PPh3)2, 140.3 mg, 0.2 mmol) was dissolved in N,N-dimethyl formamide (DMF, 10 mL), to which argon gas was bubbled for 10 min, then CuI (19 mg, 0.1 mmol) was added, the resultant reaction liquid was stirred under heating at 90° C. After 4.5 h, the reaction liquid was cooled to room temperature, water (10 mL) was added to quench the reaction. The resultant mixture was extracted with ethyl acetate (3×20 mL), the organic phases were combined, washed with water and saturated brine successively, dried over anhydrous sodium sulfate, and then concentrated, the resultant residue was purified via silica gel column chromatography (PE/EA=3:1) to yield 2.5 g of the target product as brown solid.

後処理

  1. customwas bubbled for 10 min
  2. customthe resultant reaction liquid
  3. customthe reaction liquid
  4. temperaturewas cooled to room temperature
  5. customto quench
  6. customthe reaction
  7. extractionThe resultant mixture was extracted with ethyl acetate (3×20 mL)
  8. washwashed with water and saturated brine successively
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated
  11. customthe resultant residue was purified via silica gel column chromatography (PE/EA=3:1)

出典と根拠

ORDレコード
ord-68ec179b49284b9f9b0ede08d7e23fc6
出典データセット
uspto-grants-2015_02
特許番号
US08952002B2

反応ノート

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