1,1'-Carbonyldiimidazole → methyl 2-((R)-(3-fluorophenyl)((3R)-1-((S)-1-(N-Methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-(tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamate

HRID 452017Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 452017
[NH2:1][C@@H:2]([CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][O:18][CH2:17]1)[CH2:3][N:4]([CH3:14])[C:5](=[O:13])[O:6][CH2:7][CH2:8][Si:9]([CH3:12])([CH3:11])[CH3:10].C1N=CN([C:27]([N:29]2[CH:33]=N[CH:31]=[CH:30]2)=[O:28])C=1.CCN(C(C)C)C(C)C.[CH3:43][O:44][C:45](=[O:64])[NH:46][CH2:47][CH2:48][O:49][CH:50]([C:57]1[CH:62]=[CH:61][CH:60]=[C:59]([F:63])[CH:58]=1)[CH:51]1CCCN[CH2:52]1>C(Cl)Cl>[F:63][C:59]1[CH:58]=[C:57]([C@@H:50]([C@@H:51]2[CH2:52][CH2:31][CH2:30][N:29]([C:27](=[O:28])[NH:1][C@@H:2]([CH2:15][CH:16]3[CH2:21][CH2:20][CH2:19][O:18][CH2:17]3)[CH2:3][N:4]([C:5]([O:6][CH2:7][CH2:8][Si:9]([CH3:12])([CH3:11])[CH3:10])=[O:13])[CH3:14])[CH2:33]2)[O:49][CH2:48][CH2:47][NH:46][C:45](=[O:64])[O:44][CH3:43])[CH:62]=[CH:61][CH:60]=1

Komponenten

6

Edukt 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 67365379{2-[(3-Fluoro-phenyl)-piperidin-3-yl-methoxy]-ethyl}-carbamic acid methyl esterHCID 673661002-(trimethylsilyl)ethyl (S)-2-amino-3-(tetrahydro-2H-pyran-3-yl)propyl(methyl)carbamate

Produkt 1

HCID 67365837methyl 2-((R)-(3-fluorophenyl)((3R)-1-((S)-1-(N-Methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-(tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamateAusbeute 50 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 2-(trimethylsilyl)ethyl (S)-2-amino-3-(tetrahydro-2H-pyran-3-yl)propyl(methyl)carbamate (300 mg, 0.95 mmol) and CDI (154 mg, 0.95 mmol) in anhydrous CH2Cl2 (20 mL), DIEA (612 mg, 4.7 mmol) was added with ice bath. After addition, the mixture was stirred for 1 h at 0° C., then was added to a solution of {2-[(3-fluoro-phenyl)-piperidin-3-yl-methoxy]-ethyl}-carbamic acid methyl ester (245 mg, 0.79 mmol) in anhydrous CH2Cl2 (25 mL). The reaction mixture was allowed to warm to rt and stirred overnight. After the reaction was completed, the solvent was removed in vacuo. The product was purified by preparative TLC to afford methyl 2-((R)-(3-fluorophenyl)((3R)-1-((S)-1-(N-Methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-(tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamate (258 mg, 50% yield).

Aufarbeitung

  1. additionAfter addition
  2. temperatureto warm to rt
  3. stirringstirred overnight
  4. customthe solvent was removed in vacuo
  5. customThe product was purified by preparative TLC

Quellen und Nachweise

ORD-Eintrag
ord-d56fe6c0cd0842a4bb343eaf5e3fe4d3
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08487108B2

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