Diisopropylethylamine → Biphenyl-2-ylcarbamic Acid 1-[2-({3-[2-(3-{(S)-2-[(R)-2-(tert-Butyldimethylsilanyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]propyl}phenyl)acetylamino]propyl}methylcarbamoyl)ethyl]piperidin-4-yl Ester

HRID 1097037노트

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HRID 1097037 반응식
[Si:1]([O:8][C@H:9]([C:25]1[CH:34]=[CH:33][C:32]([OH:35])=[C:31]2[C:26]=1[CH:27]=[CH:28][C:29](=[O:36])[NH:30]2)[CH2:10][NH:11][C@@H:12]([CH3:24])[CH2:13][C:14]1[CH:15]=[C:16]([CH2:20][C:21](O)=[O:22])[CH:17]=[CH:18][CH:19]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[O-]S(C(F)(F)F)(=O)=O.C(N(CC)C(C)C)(C)C.[NH2:54][CH2:55][CH2:56][CH2:57][N:58]([CH3:85])[C:59]([CH2:61][CH2:62][N:63]1[CH2:68][CH2:67][CH:66]([O:69][C:70](=[O:84])[NH:71][C:72]2[CH:77]=[CH:76][CH:75]=[CH:74][C:73]=2[C:78]2[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=2)[CH2:65][CH2:64]1)=[O:60]>CN(C=O)C>[Si:1]([O:8][C@H:9]([C:25]1[CH:34]=[CH:33][C:32]([OH:35])=[C:31]2[C:26]=1[CH:27]=[CH:28][C:29](=[O:36])[NH:30]2)[CH2:10][NH:11][C@@H:12]([CH3:24])[CH2:13][C:14]1[CH:15]=[C:16]([CH2:20][C:21]([NH:54][CH2:55][CH2:56][CH2:57][N:58]([CH3:85])[C:59]([CH2:61][CH2:62][N:63]2[CH2:64][CH2:65][CH:66]([O:69][C:70](=[O:84])[NH:71][C:72]3[CH:77]=[CH:76][CH:75]=[CH:74][C:73]=3[C:78]3[CH:79]=[CH:80][CH:81]=[CH:82][CH:83]=3)[CH2:67][CH2:68]2)=[O:60])=[O:22])[CH:17]=[CH:18][CH:19]=1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 2758875TrifluoromethanesulfonateHCID 66770193(3-{(S)-2-[(R)-2-(tert-butyldimethylsilanyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]propyl}phenyl)acetic acidHCID 66770333Biphenyl-2-ylcarbamic acid 1-{2-[(3-aminopropyl)methylcarbamoyl]ethyl}piperidin-4-yl ester

생성물 1

HCID 86646964Biphenyl-2-ylcarbamic Acid 1-[2-({3-[2-(3-{(S)-2-[(R)-2-(tert-Butyldimethylsilanyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]propyl}phenyl)acetylamino]propyl}methylcarbamoyl)ethyl]piperidin-4-yl Ester수율 24%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A mixture of (3-{(S)-2-[(R)-2-(tert-butyldimethylsilanyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]propyl}phenyl)acetic acid (135 mg, 0.264 mmol); 2-chloropyridium triflate on Wang resin (polymer-supported Mukaiyama reagent) (1.19 mmol/g loading; 635 mg, 0.775 mmol) and N,N-diisopropylethylamine (132 μL, 0.755 mmol) in DMF (4.78 mL) was stirred at room temperature for 30 min. Biphenyl-2-ylcarbamic acid 1-{2-[(3-aminopropyl)methylcarbamoyl]ethyl}piperidin-4-yl ester (122 mg, 0.278 mmol) was added and this mixture was stirred at room temperature overnight. The mixture was filtered and the resin was washed with DCM (4 mL), MeOH (4 mL) and THF (4 mL). The filtrate was concentrated under reduced pressure and the residue was dissolved in DCM. This solution was washed with water (2×10 mL), saturated aqueous sodium bicarbonate (2×10 mL) and brine (1×10 mL); and then dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-20% MeOH in DCM) to give the title compound (59 mg, 24% yield) as a white solid.

후처리

  1. filtrationThe mixture was filtered
  2. washthe resin was washed with DCM (4 mL), MeOH (4 mL) and THF (4 mL)
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. dissolutionthe residue was dissolved in DCM
  5. washThis solution was washed with water (2×10 mL), saturated aqueous sodium bicarbonate (2×10 mL) and brine (1×10 mL)
  6. dry with materialand then dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel flash chromatography (0-20% MeOH in DCM)

출처 및 근거

ORD 기록
ord-1346c8d0512447ad966175ccd3274b09
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08138345B2

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