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Sodium hydride → Diethyl {2-[4-({[2-[(tert-butoxycarbonyl)amino]-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]-1-cyanoethyl}phosphonate

HRID 1013467
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HRID 1013467 반응식
[C:1]([CH2:3][P:4](=[O:11])([O:8][CH2:9][CH3:10])[O:5][CH2:6][CH3:7])#[N:2].[H-].[Na+].Br[CH2:15][C:16]1[CH:43]=[CH:42][C:19]([C:20]([NH:22][C:23]2[CH:28]=[C:27]([C:29]3[S:30][CH:31]=[CH:32][CH:33]=3)[CH:26]=[CH:25][C:24]=2[NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:21])=[CH:18][CH:17]=1>C1COCC1.C(OCC)(=O)C>[C:37]([O:36][C:35]([NH:34][C:24]1[CH:25]=[CH:26][C:27]([C:29]2[S:30][CH:31]=[CH:32][CH:33]=2)=[CH:28][C:23]=1[NH:22][C:20]([C:19]1[CH:42]=[CH:43][C:16]([CH2:15][CH:3]([P:4](=[O:11])([O:8][CH2:9][CH3:10])[O:5][CH2:6][CH3:7])[C:1]#[N:2])=[CH:17][CH:18]=1)=[O:21])=[O:41])([CH3:40])([CH3:39])[CH3:38]
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6

반응물 3

HCID 24758Sodium hydrideHCID 75676Diethyl (cyanomethyl)phosphonateHCID 57925962Tert-butyl [2-{[4-(bromomethyl)benzoyl]amino}-4-(2-thienyl)phenyl]carbamate

생성물 1

HCID 57925835Diethyl {2-[4-({[2-[(tert-butoxycarbonyl)amino]-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]-1-cyanoethyl}phosphonate

시약·촉매·용매 2

HCID 8028Tetrahydrofuran
용매
2회
HCID 8857Ethyl Acetate용매

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온도
0 °C

실험 절차

Diethyl cyanomethylphosphonate (0.19 ml, 1.175 mmol) was dissolved in THF (7 ml). The solution was cooled to 0° C. Sodium hydride (0.0818 g, 2.045 mmol) was added to the reaction. The reaction was allowed to stir for several minutes. Tert-butyl [2-{[4-(bromomethyl)benzoyl]amino}-4-(2-thienyl)phenyl]carbamate (0.5047 g, 1.035 mmol) was added in a solution of THF. The reaction was allowed to slowly warm to room temperature and stir overnight. The reaction was diluted with ethyl acetate and quenched with saturated aqueous ammonium chloride. The aqueous layer was extracted with ethyl acetate three times. The combined organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting residue was partially purified by column chromatography on silica gel. MS: cal'd 484 (MH+-Boc), exp 484 (MH+-Boc).

후처리

  1. temperatureto slowly warm to room temperature
  2. stirringstir overnight
  3. customquenched with saturated aqueous ammonium chloride
  4. extractionThe aqueous layer was extracted with ethyl acetate three times
  5. dry with materialThe combined organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was partially purified by column chromatography on silica gel

출처 및 근거

ORD 기록
ord-110ee8e2c6ce496f9a8df98e24943375
출처 데이터셋
uspto-grants-2011_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07981874B2

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