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Diphosgene → (2S,3S)-2-{2,5-dioxo-4-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-imidazolidin-1-yl}-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide

HRID 32820
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HRID 32820 반응식
[NH2:1][C@H:2]([C:27]1[CH:32]=[CH:31][C:30]([O:33][CH2:34][CH2:35][N:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)=[CH:29][CH:28]=1)[C:3]([NH:5][C@@H:6]([C@H:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH3:20])[C:7]([NH:9][C:10]1[S:11][CH:12]=[C:13]([C:15](=[O:18])[CH2:16][CH3:17])[N:14]=1)=[O:8])=[O:4].C(N(C(C)C)CC)(C)C.[O:51]=[C:52](Cl)OC(Cl)(Cl)Cl>O1CCCC1>[O:51]=[C:52]1[NH:1][CH:2]([C:27]2[CH:28]=[CH:29][C:30]([O:33][CH2:34][CH2:35][N:36]3[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41]3)=[CH:31][CH:32]=2)[C:3](=[O:4])[N:5]1[C@@H:6]([C@H:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH3:20])[C:7]([NH:9][C:10]1[S:11][CH:12]=[C:13]([C:15](=[O:18])[CH2:16][CH3:17])[N:14]=1)=[O:8]
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참가 물질

5

반응물 3

HCID 10426DiphosgeneHCID 81531DiisopropylethylamineHCID 86603385(2S,3S)-2-{(R)-2-amino-2-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-acetylamino}-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide

생성물 1

HCID 11527277(2S,3S)-2-{2,5-dioxo-4-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-imidazolidin-1-yl}-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide수율 35.9%

시약·촉매·용매 1

HCID 8028
Tetrahydrofuran
용매
2회

실험 절차

Crude (2S,3S)-2-{(R)-2-amino-2-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-acetylamino}-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide (≈0.16 mmol) was dissolved in tetrahydrofuran (10 mL) that contained diisopropylethylamine (142 μL, 105 mg, 0.81 mmol) and was transferred via cannula to a solution of diphosgene (14 μL, 23 mg, 0.12 mmol) in tetrahydrofuran (15 mL) at 0° C. The reaction mixture was stirred for 20 minutes and then partitioned between ethyl acetate and water. The organic layer was separated and dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography over silica gel eluted first with ethyl acetate and then gradient eluted with dichloromethane containing from 0 to 10% methanol. Precipitation of the isolated product from dichloromethane with an excess of hexanes gave (2S,3S)-2-{2,5-dioxo-4-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-imidazolidin-1-yl}-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide as a white solid (26 mg, 27%).

후처리

  1. custompartitioned between ethyl acetate and water
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by chromatography over silica gel
  7. washeluted first with ethyl acetate
  8. washgradient eluted with dichloromethane containing from 0 to 10% methanol
  9. customPrecipitation of the isolated product from dichloromethane with an excess of hexanes

출처 및 근거

ORD 기록
ord-aaed209479704dfface6349d9138a5dc
출처 데이터셋
uspto-grants-2008_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07427635B2

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