반응 #1144289

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5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

Intermediate 1

5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

Ethynylcyclopropane

→

title compound

수율 91.3%

5-(Cyclopropylethynyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

수율 91.3%

용매

triethylamine

반응 조건

후처리

1. 1
   기타The flask was degassed with three vacuum/N2 cycles
2. 2
   기타The flask was again degassed with three vacuum/N2 cycles
3. 3
   기타Upon completion, the solvent was evaporated
4. 4
   workup.ADDITIONThe residue was diluted with dichloromethane (600 mL)
5. 5
   세척washed with water (2×200 mL) and brine (200 mL)
6. 6
   건조dried over anhydrous sodium sulfate
7. 7
   농축concentrated in vacuo
8. 8
   기타The residue was further purified on silica gel column (1:100-1:20 EtOAc/petroleum ether)

실험 절차

A 1 L three-necked round bottom flask was charged with 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (31.2 g, 111 mmol; Intermediate 1) and triethylamine (500 mL). The flask was degassed with three vacuum/N2 cycles, followed by the addition of Pd(PPh3)2Cl2 (7.7 g, 11 mmol) and CuI (2.1 g, 11 mmol) under N2 atmosphere. The flask was again degassed with three vacuum/N2 cycles. Ethynylcyclopropane (70% in toluene, 20.9 g, 222 mmol) was then added via syringe and the reaction mixture was stirred at 80° C. for 16 hours. Upon completion, the solvent was evaporated. The residue was diluted with dichloromethane (600 mL), washed with water (2×200 mL) and brine (200 mL), dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was further purified on silica gel column (1:100-1:20 EtOAc/petroleum ether) affording the title compound (27.0 g). 1H NMR (400 MHz, DMSO-d6): δ 8.09 (s, 1H), 7.82 (s, 1H), 7.70 (d, 1H), 7.39 (m, 1H), 5.84 (dd, 1H), 3.91-3.87 (m, 1H), 3.78-3.73 (m, 1H), 2.52-2.37 (m, 1H), 2.05-1.94 (m, 2H), 1.76-1.72 (m, 1H), 1.60-1.52 (m, 3H), 0.92-0.87 (m, 2H), 0.78-0.73 (m, 2H); LCMS: 267 (M+H)+.

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