Diisopropylethylamine → N2-(9-fluorenylmethoxycarbonyl)-N5-(4-(2,2-bis(diallylphosphoryl)ethyl)phenyl)-L-glutamine

HRID 39273노트

반응식

HRID 39273 반응식
[NH:1]([C:15]([O:17][CH2:18][CH:19]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:25]2[C:20]1=[CH:21][CH:22]=[CH:23][CH:24]=2)=[O:16])[C@H:2]([C:8]([O:10]C(C)(C)C)=[O:9])[CH2:3][CH2:4][C:5](=[O:7])O.CCN([CH:38]([CH3:40])[CH3:39])C(C)C.CN(C(ON1N=NC2C=C[CH:54]=[CH:55][C:50]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:65][C:66]1[CH:81]=[CH:80][C:69]([CH2:70][CH:71]([P:76](=[O:79])([O-])[O-])[P:72](=[O:75])([O-])[O-])=[CH:68][CH:67]=1>CN(C=O)C.C(Cl)Cl>[CH:30]1[C:31]2[CH:19]([CH2:18][O:17][C:15]([NH:1][C@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][C:5](=[O:7])[NH:65][C:66]3[CH:67]=[CH:68][C:69]([CH2:70][CH:71]([P:72]([CH2:40][CH:38]=[CH2:39])([CH2:50][CH:55]=[CH2:54])=[O:75])[P:76]([CH2:20][CH:19]=[CH2:18])([CH2:8][CH:2]=[CH2:3])=[O:79])=[CH:80][CH:81]=3)=[O:16])[C:20]3[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:26]=2[CH:27]=[CH:28][CH:29]=1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 7017912(4S)-5-(tert-Butoxy)-4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-oxopentanoic acidHCID 200590851-(4-Aminobenzyl)methylenebisphosphonate

생성물 1

HCID 86762032N2-(9-fluorenylmethoxycarbonyl)-N5-(4-(2,2-bis(diallylphosphoryl)ethyl)phenyl)-L-glutamine

시약·촉매·용매 2

HCID 6228Dimethylformamide용매2회HCID 6344Dichloromethane용매

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온도
0 °C

실험 절차

To a solution of Fmoc-Glu-Ot-Bu (253 mg, 0.59 mmol) in DMF (3 mL) at 0° C. was added DIEA (207 μL, 1.19 mmol) and HBTU (225 mg, 0.59 mmol). After stirring for 10 min at 0° C., aminobenzyl bisphosphonate 104 (262 mg, 0.59 mmol) in DMF (2 mL) was added and stirring was pursued for 2 h at 0° C. The reaction mixture was diluted with CH2Cl2, washed with H2O, 0.5N HCl solution, saturated NaHCO3 solution and saturated NaCl solution. The organic layer was dried over MgSO4, filtered and concentrated to dryness. The crude product was purified by silica gel chromatography on a Biotage™ flash chromatography system using 1-10% methanol in CH2Cl2. Compound 105 was obtained as a yellow gum (431 mg, 86%). 1H NMR (400 MHz, CDCl3) δ 1.46 (s, 9H), 1.86-1.92 (m, 1H), 2.26-2.38 (m, 3H), 2.70 (tt, J=24.0, 6.3 Hz, 1H), 3.24 (dt, J=16.8, 6.3 Hz, 2H), 4.19-4.29 (m, 2H), 4.40-4.60 (m, 10H), 5.19-5.22 (m, 4H), 5.28-5.34 (m, 4H), 5.58 (d, J=8.0 Hz, 1H), 5.83-5.93 (m, 4H), 7.21 (d, J=8.3, 2H), 7.27-7.34 (m, 2H), 7.38-7.43 (m, 2H), 7.50 (d, J=8.2 Hz, 2H), 7.60 (d, J=7.4 Hz, 2H), 7.77 (d, J=7.5 Hz, 2H), 8.28 (s, 1H).

후처리

  1. stirringstirring
  2. waitwas pursued for 2 h at 0° C
  3. washwashed with H2O, 0.5N HCl solution, saturated NaHCO3 solution and saturated NaCl solution
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe crude product was purified by silica gel chromatography on a Biotage™ flash chromatography system

출처 및 근거

ORD 기록
ord-b88715a941f946c08de545f661a27637
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524691B2

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