Water → HCID 178456684, 화합물

HRID 1629524노트

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HRID 1629524 반응식
Cl.[CH2:2]([O:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]([NH2:16])=[NH:15])=[C:12]([F:19])[CH:11]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(=O)([O-])O.[K+].O.Cl[CH2:27][C:28]([C:30]1[N:31]([CH:35]([CH3:37])[CH3:36])[N:32]=[CH:33][N:34]=1)=O>C1COCC1.[Na+].[Cl-]>[CH2:2]([O:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]2[NH:16][CH:27]=[C:28]([C:30]3[N:31]([CH:35]([CH3:37])[CH3:36])[N:32]=[CH:33][N:34]=3)[N:15]=2)=[C:12]([F:19])[CH:11]=1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 516893Potassium BicarbonateHCID 197001614-Benzyloxy-2-fluoro-benzamidine hydrochlorideHCID 712991852-chloro-1-(1-isopropyl-1H-1,2,4-triazol-5-yl)ethanone

생성물 1

HCID 178456684HCID 178456684, 화합물수율 84%

시약·촉매·용매 2

HCID 5234Sodium Chloride용매HCID 8028Tetrahydrofuran용매

실험 절차

A solution of 4-benzyloxy-2-fluoro-benzamidine hydrochloride (74.5 g, 0.265 mol) in THF (705 mL) was treated with potassium hydrogen carbonate (106 g, 1.06 mol) and H2O (150 mL). The resultant mixture was heated to reflux to give a white suspension. Whilst maintaining gentle reflux and mechanical stirring (500 rpm) a solution of 2-chloro-1-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-ethanone (50 g, 0.265 mol) was added dropwise over 40 min. The resultant suspension gradually dissolved giving a dark red mixture that was refluxed for 18 h. The mixture was cooled to RT, diluted with saturated aqueous NaCl solution (500 mL) and extracted with EtOAc (500 mL). The organic extract was washed with saturated aqueous NaCl solution, dried over Na2SO4, filtered and concentrated in vacuo to give a pink solid The solid was triturated in a mixture of MTBE/pentane (1:1 by volume, 300 mL), collected by filtration, washed with a MTBE/pentane mixture and dried in vacuo to give 5-[2-(4-Benzyloxy-2-fluoro-phenyl)-1H-imidazol-4-yl]-1-isopropyl-1H-[1,2,4]triazole as a pale pink solid (84 g, 84%). 1H NMR (400 MHz, d6-DMSO): 7.95-7.93 (2 H, m), 7.76 (1 H, s), 7.44-7.42 (5 H, m), 7.12 (1 H, dd, J=13.10, 2.52 Hz), 7.03 (1 H, dd, J=8.74, 2.47 Hz), 5.90 (1 H, m), 5.21 (2 H, s), 1.46 (6 H, d, J=6.60 Hz).

후처리

  1. temperatureto reflux
  2. customto give a white suspension
  3. temperatureWhilst maintaining gentle
  4. temperaturereflux
  5. additionwas added dropwise over 40 min
  6. customgiving a dark red mixture that
  7. temperaturewas refluxed for 18 h
  8. extractionextracted with EtOAc (500 mL)
  9. extractionThe organic extract
  10. washwas washed with saturated aqueous NaCl solution
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customto give a pink solid The solid
  15. customwas triturated in a mixture of MTBE/pentane (1:1 by volume, 300 mL)
  16. filtrationcollected by filtration
  17. washwashed with a MTBE/pentane mixture
  18. customdried in vacuo

출처 및 근거

ORD 기록
ord-b3238293dfff4bc99a2fa49e413d9c6d
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785626B2

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