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 1055314ノート

反応式

HRID 1055314 の反応式
[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]

参加物

6

反応物 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

生成物 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 Ester収率 24%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-9fc29bc79c0a4d87be9c04975d90f8bd
出典データセット
uspto-grants-2016_07
特許番号
US09394275B2

反応ノート

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