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

HRID 447446노트

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HRID 447446 반응식
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

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 3283Diethyl Ether용매

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온도
90 °C

실험 절차

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-25 g, 5-15% MeOH in DCM) yielded an impure product. A second chromatography on Biotage (silica, SNAP-25 g, 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.

후처리

  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-25 g, 5-15% MeOH in DCM) yielded an impure product

출처 및 근거

ORD 기록
ord-f5a4d3694e204932a90af4a4ce3e32fc
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481525B2

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