Trityl chloride → (S)-4-(1-benzyl-2-trityloxy-ethylamino)-3-[6-bromo-4-methyl-1H-benzimidazole-2-yl]-1H-pyridin-2-one

HRID 1793708노트

반응식

HRID 1793708 반응식
[CH2:1]([C@H:8]([NH:11][C:12]1[CH:17]=[CH:16][NH:15][C:14](=[O:18])[C:13]=1[C:19]1[NH:23][C:22]2[CH:24]=[C:25]([Br:29])[CH:26]=[C:27]([CH3:28])[C:21]=2[N:20]=1)[CH2:9][OH:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[C:36]1([C:42](Cl)([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>C1COCC1>[CH2:1]([C@H:8]([NH:11][C:12]1[CH:17]=[CH:16][NH:15][C:14](=[O:18])[C:13]=1[C:19]1[NH:23][C:22]2[CH:24]=[C:25]([Br:29])[CH:26]=[C:27]([CH3:28])[C:21]=2[N:20]=1)[CH2:9][O:10][C:42]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)([C:49]1[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=1)[C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

참가 물질

5

반응물 3

HCID 6456Trityl chlorideHCID 10796Cesium carbonateHCID 136118015(S)-3-(6-bromo-4-methyl-1H-benzo[d]imidazol-2-yl)-4-(1-hydroxy-3-phenylpropan-2-ylamino)pyridin-2(1H)-one

생성물 1

HCID 136365126(S)-4-(1-benzyl-2-trityloxy-ethylamino)-3-[6-bromo-4-methyl-1H-benzimidazole-2-yl]-1H-pyridin-2-one수율 73%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of (S)-4-(1-benzyl-2-hydroxy-ethylamino)-3-(6-bromo-4-methyl-1H-benzimidazol-2-yl)-1H-pyridin-2-one (0.9 g, 1.98 mmol) in THF (30 mL), was added Cs2CO3 (1.29 g, 3.96 mmol) followed by triphenylmethyl chloride (1.10 g, 3.96 mmol). The reaction mixture was heated to reflux for 14 h under nitrogen and then cooled to room temperature. After removal of the solvent, the residue was diluted with ethyl acetate and washed with water. The aqueous fraction was extracted with ethyl acetate and the combined organic layers were washed with water and brine, dried over Na2SO4. After concentration in vacuo, the residue was purified by flash column chromatography (30% EtOAc/hexane) to yield the title compound (1 g, 73%) as a white solid. 1N NMR (300 MHz, DMSO-d6) δ 11.77 (1H, broad s), 11.73 (1H, d, J=5.2 Hz), 11.46 (1H, broad s), 7.13–7.54 (23H, m), 5.87 (1H, d, J=4.5 Hz), 4.09–4.14 (1H, m), 3.07–3.42 (4H, m), 2.54 (3H, s). LCMS (M+H)+ m/z 695 (t=2.79 min.).

후처리

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 14 h under nitrogen
  3. customAfter removal of the solvent
  4. additionthe residue was diluted with ethyl acetate
  5. washwashed with water
  6. extractionThe aqueous fraction was extracted with ethyl acetate
  7. washthe combined organic layers were washed with water and brine
  8. dry with materialdried over Na2SO4
  9. concentrationAfter concentration in vacuo
  10. customthe residue was purified by flash column chromatography (30% EtOAc/hexane)

출처 및 근거

ORD 기록
ord-d27feae59ba64f999664ce3ebcec9fe0
출처 데이터셋
uspto-grants-2006_07
특허 번호
US07081454B2

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