Triphenylphosphine → 1-[7-(2-{[3-(1-Piperazinyl)-2-pyrazinyl]oxy}ethoxy)-1-benzofuran-2-yl]-1-ethanone, Hydrochloride

HRID 991639노트

반응식

HRID 991639 반응식
CCOC(/N=N/C(OCC)=O)=O.C(OC([N:20]1[CH2:25][CH2:24][N:23]([C:26]2[C:27]([O:32][CH2:33][CH2:34][OH:35])=[N:28][CH:29]=[CH:30][N:31]=2)[CH2:22][CH2:21]1)=O)(C)(C)C.[C:36]([C:39]1[O:40][C:41]2[C:47](O)=[CH:46][CH:45]=[CH:44][C:42]=2[CH:43]=1)(=[O:38])[CH3:37].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[ClH:68].[NH+]1C=CC=CC=1>C1COCC1.CO.O>[ClH:68].[N:23]1([C:26]2[C:27]([O:32][CH2:33][CH2:34][O:35][C:47]3[C:41]4[O:40][C:39]([C:36](=[O:38])[CH3:37])=[CH:43][C:42]=4[CH:44]=[CH:45][CH:46]=3)=[N:28][CH:29]=[CH:30][N:31]=2)[CH2:22][CH2:21][NH:20][CH2:25][CH2:24]1

참가 물질

9

반응물 5

HCID 11776TriphenylphosphineHCID 5953292-Acetyl-7-hydroxybenzofuranHCID 5462977Diethyl azodicarboxylateHCID 114160742-[3-(4-Tert-butoxycarbonyl-1-piperazinyl)-2-pyrazinyloxy]ethanolHCID 21584435Pyridinium hydrochloride

생성물 1

HCID 1317235481-[7-(2-{[3-(1-Piperazinyl)-2-pyrazinyl]oxy}ethoxy)-1-benzofuran-2-yl]-1-ethanone, Hydrochloride수율 99.2%

시약·촉매·용매 3

HCID 887Methanol용매HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

DEAD (0.787 mL, 5.00 mmol) was added to a stirred solution of 2-[3-(4-tert-butoxycarbonyl-1-piperazinyl)-2-pyrazinyloxy]ethanol (1.50 g, 4.63 mmol; prepared in Example 52, Step 2), 2-acetyl-7-hydroxybenzofuran (0.88 g, 5.0 mmol) and PPh3 (1.31 g, 5.0 mmol) in THF (3 mL) under gentle heating. After being stirred for 30 min at room temperature, the reaction mixture was poured into water, extracted with EtOAc, dried (MgSO4) and concentrated. The residue was purified by column chromatography on silica using toluene/EtOAc (7:3) as eluent. The pure fractions were combined and treated with CH2Cl2/TFA/H2O (50:45:5; 5 mL) for 30 min at room temperature. The mixture was poured into 0.5 M aqueous HCl and washed with EtOAc. The aqueous layer was alkalinized, by addition of NaOH, to pH 12 and extracted with EtOAc. The organic layer was dried (MgSO4), filtered and concentrated. The residue (0.250 g, 0.65 mmol) and pyridinium hydrochloride (0.075 g, 0.65 mmol) was dissolved in MeOH. The mixture was and concentrated and the residue was re-dissolved in EtOH and concentrated three more times to give 0.27 g (14%) of the title product. Pos-EI-MS shows M+ and 19 ions supporting the stated structure. HRMS m/z calcd for C20H22N4O4 (M)+ 382.1641, found 382.1631.

후처리

  1. extractionextracted with EtOAc
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customThe residue was purified by column chromatography on silica
  5. additiontreated with CH2Cl2/TFA/H2O (50:45:5; 5 mL) for 30 min at room temperature
  6. additionThe mixture was poured into 0.5 M aqueous HCl
  7. washwashed with EtOAc
  8. additionThe aqueous layer was alkalinized, by addition of NaOH, to pH 12
  9. extractionextracted with EtOAc
  10. dry with materialThe organic layer was dried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. concentrationconcentrated
  14. dissolutionthe residue was re-dissolved in EtOH
  15. concentrationconcentrated three more times

출처 및 근거

ORD 기록
ord-75692a84465c4ff684a4744d659a1a07
출처 데이터셋
uspto-grants-2002_10
특허 번호
US06465467B1

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