Ethyl cyanoformate → Ethyl 5-(2-fluoro-4-methoxyphenyl)-6-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole-3-carboxylate

HRID 1054802노트

반응식

HRID 1054802 반응식
[F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[C:10]1[C:18]([CH3:19])=[CH:17][C:16]2[C:12](=[CH:13][N:14]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[N:15]=2)[CH:11]=1.[Li]CCCC.[C:33](C#N)(=[O:37])[O:34][CH2:35][CH3:36]>C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[C:10]1[C:18]([CH3:19])=[CH:17][C:16]2[C:12](=[C:13]([C:33]([O:34][CH2:35][CH3:36])=[O:37])[N:14]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:25])([CH3:27])[CH3:26])[N:15]=2)[CH:11]=1

참가 물질

5

반응물 3

HCID 69336Ethyl cyanoformateHCID 866987935-(2-Fluoro-4-methoxyphenyl)-6-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazoleHCID 178418339Butyllithium

생성물 1

HCID 86698794Ethyl 5-(2-fluoro-4-methoxyphenyl)-6-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole-3-carboxylate수율 58.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
-78 °C

실험 절차

To a solution of 5-(2-fluoro-4-methoxyphenyl)-6-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole (650 mg, 1.68 mmol) in THF (10 mL) at −78° C. was added n-BuLi (2.5 M in hexanes, 0.74 mL, 1.85 mmol) dropwise via syringe. The reaction was stirred at −78° C. for 10 minutes, warmed to room temperature for 5 minutes, and cooled back to −78° C. A solution of ethyl cyanocarbonate (188 mg, 1.90 mmol) in THF (1 mL) was added via syringe. The cooling bath was removed and the reaction mixture was stirred at room temperature for 30 minutes. The reaction was quenched with aqueous NH4Cl solution and diluted with EtOAc. The organic layer was washed with water and brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography (0-20% EtOAc/heptane) to provide the title compound (448 mg, 58% yield). MS (ES+) 459.3 (M+H)+. 1H NMR (500 MHz, CDCl3) δ 7.87 (s, 1H), 7.69 (s, 1H), 7.22 (t, J=8.54 Hz, 1H), 6.81 (dd, J=8.42, 2.32 Hz, 1H), 6.75 (dd, J=11.34, 2.32 Hz, 1H), 6.20 (s, 2H), 4.49 (q, J=7.07 Hz, 2H), 3.89 (s, 3H), 3.66-3.72 (m, 2H), 2.29 (s, 3H), 1.44 (t, J=7.07 Hz, 3H), 0.93-1.00 (m, 2H), 0.00 (s, 9H).

후처리

  1. temperaturewarmed to room temperature for 5 minutes
  2. temperaturecooled back to −78° C
  3. customThe cooling bath was removed
  4. stirringthe reaction mixture was stirred at room temperature for 30 minutes
  5. customThe reaction was quenched with aqueous NH4Cl solution
  6. additiondiluted with EtOAc
  7. washThe organic layer was washed with water and brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography (0-20% EtOAc/heptane)

출처 및 근거

ORD 기록
ord-d2f19b8d5d734dc9ad4dd28eabce5235
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394285B2

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