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

HRID 39273

反応式

HRID 39273 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-b88715a941f946c08de545f661a27637
出典データセット
uspto-grants-2013_09
特許番号
US08524691B2

関連ノート

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