Piperidine → 1-Methyl-4-(5-((trimethylsilyl)ethynyl)pyridin-2-yl)piperazine

HRID 447300ノート

反応式

HRID 447300 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.N1CCCCC1.[CH3:21][Si:22]([C:25]#[CH:26])([CH3:24])[CH3:23].CCN(CC)CC>CCOCC.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>[CH3:14][N:11]1[CH2:12][CH2:13][N:8]([C:5]2[CH:4]=[CH:3][C:2]([C:26]#[C:25][Si:22]([CH3:24])([CH3:23])[CH3:21])=[CH:7][N:6]=2)[CH2:9][CH2:10]1

参加物

8

反応物 4

HCID 8082PiperidineHCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 164142065-Bromo-2-(4-methylpiperazin-1-yl)pyridine

生成物 1

HCID 667304181-Methyl-4-(5-((trimethylsilyl)ethynyl)pyridin-2-yl)piperazine収率 61%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 3283Diethyl Ether溶媒

反応条件

温度
90 °C

実験手順

A mixture of 1-(5-bromopyridin-2-yl)-4-methylpiperazine (501.7 mg, 1.96 mmol), PdCl2(PPh3)2 (51.1 mg, 0.073 mmol) and copper(I) iodide (39.9 mg, 0.21 mmol) was flushed with argon for 10 min prior to addition of piperidine (1.25 mL, 12.7 mmol) and trimethylsilylacetylene (1.40 mL, 9.9 mmol). The resulting mixture was heated at 90° C. in a sealed vial for 3 d. The reaction mixture was cooled to room temperature and the volatiles were removed in vacuo. Chromatography on Biotage (silica, SNAP-25g, 5-15% MeOH in DCM) yielded an impure product. A second chromatography on Biotage (silica, SNAP-25g, 0-3% Et3N in Et2O) gave 1-methyl-4-(5-((trimethylsilyl)ethynyl)pyridin-2-yl)piperazine (325.7 mg, 61%). 1H NMR (400 MHz, CDCl3) δ ppm 8.29 (d, J=1.3 Hz, 1H), 7.53 (dd, J=8.9, 2.4 Hz, 1H), 6.55 (d, J=8.8 Hz, 1H), 3.67-3.52 (m, 4H), 2.57-2.44 (m, 4H), 2.35 (s, 3H); MS ESI [M+H]+ 274.0, calcd for [C15H23N3Si+H]+ 274.2.

後処理

  1. customwas flushed with argon for 10 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customthe volatiles were removed in vacuo
  4. customChromatography on Biotage (silica, SNAP-25g, 5-15% MeOH in DCM) yielded an impure product

出典と根拠

ORDレコード
ord-ec97394eedcd41038e7c50c5bb488f79
出典データセット
uspto-grants-2013_07
特許番号
US08481533B2

反応ノート

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