Piperidine → HCID 57545919, 화합물

HRID 913845

반응식

HRID 913845 반응식
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH:11]([O:13][CH2:14][C:15]3([C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=4)[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]3)[CH3:12])[CH:10]=1)[N:7](COCC[Si](C)(C)C)[N:6]=[CH:5]2.N1CCCCC1.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>FC(F)(F)C(O)=O.ClCCl>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH:11]([O:13][CH2:14][C:15]3([C:28]4[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=4)[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:26])([CH3:27])[CH3:25])=[O:22])[CH2:17][CH2:16]3)[CH3:12])[CH:10]=1)[NH:7][N:6]=[CH:5]2

참가 물질

6

반응물 3

HCID 8082PiperidineHCID 90495Di-tert-butyl dicarbonateHCID 57545992(+/-)-tert-Butyl 4-((1-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

생성물 1

HCID 57545919HCID 57545919, 화합물

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 6422Trifluoroacetic acid용매

실험 절차

(±)-tert-Butyl 4-((1-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (543 mg, 0.819 mmol) was dissolved in trifluoroacetic acid (50% in dichloromethane, 10 mL) and stirred at room temperature for 4 h. The reaction was concentrated and loaded onto a strong cation exchange cartridge in methanol. After washing with several volumes of methanol, the product was eluted with 2M ammonia in methanol. Concentration gave the crude piperidine. The piperidine was dissolved in dichloromethane (5 mL) and treated with di-tert-butyl dicarbonate (224 mg, 1.02 mmol). After 1 h, the reaction was quenched by addition of 2M ammonia in methanol and concentrated. The residue was suspended in water and extracted with diethyl ether. The ethereal was washed with water, then brine, dried over magnesium sulfate, and concentrated. Column chromatography (EtOAc/Hex) gave 420 mg (96%). 1H-NMR (CDCl3, 500 MHz) δ 10.05 (bs, 1H), 7.89 (s, 1H), 7.71 (d, J=1.8, 1H), 7.23 (m, 2H), 7.08 (d, J=1.5, 1H), 7.02 (m, 2H), 4.48 (q, J=6.7, 1H), 3.70 (m, 2H), 3.34 (d, J=9.2, 1H), 3.23 (d, J=8.9, 1H), 3.03 (m, 1H), 2.95 (m, 1H), 2.21 (m, 1H), 2.03 (m, 1H), 1.82 (m, 1H), 1.72 (m, 1H), 1.41 (s, 9H), 1.40 (d, J=6.7, 3H); 13C NMR (126 MHz, CDCl3) δ ppm 162.6, 160.6, 155.0, 138.1, 135.9, 133.7, 128.7 (d, J=7.7), 127.9, 126.5, 125.5, 122.3, 115.7, 115.6, 113.6, 79.6, 78.6, 78.0, 41.2, 40.1, 32.5, 32.1, 28.5, 22.2, 14.3.

후처리

  1. concentrationThe reaction was concentrated
  2. washAfter washing with several volumes of methanol
  3. washthe product was eluted with 2M ammonia in methanol
  4. concentrationConcentration
  5. customgave the crude piperidine
  6. waitAfter 1 h
  7. customthe reaction was quenched by addition of 2M ammonia in methanol
  8. concentrationconcentrated
  9. extractionextracted with diethyl ether
  10. washThe ethereal was washed with water
  11. dry with materialbrine, dried over magnesium sulfate
  12. concentrationconcentrated
  13. customColumn chromatography (EtOAc/Hex) gave 420 mg (96%)

출처 및 근거

ORD 기록
ord-9850382c78b94810a560608fc5918e6e
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08026257B2

연결된 노트

불러오는 중…