Dimethyl Sulfoxide → (1-benzylcyclohexyl)methyl(1S)-5-[(4-morpholinylcarbonyl)amino]-1-(oxo{[(1R)-1-phenylethyl]amino}acetyl)pentylcarbamate

HRID 1180749Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1180749
C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][CH:12]([C@@H:24]([NH:38][C:39](=[O:55])[O:40][CH2:41][C:42]1([CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]1)[CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30]([N:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1)=[O:31])[C:13](=[O:23])[NH:14][C@@H:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH3:16].C(N(CC)CC)C>ClCCl>[N:32]1([C:30]([NH:29][CH2:28][CH2:27][CH2:26][CH2:25][C@H:24]([NH:38][C:39](=[O:55])[O:40][CH2:41][C:42]2([CH2:48][C:49]3[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=3)[CH2:43][CH2:44][CH2:45][CH2:46][CH2:47]2)[C:12](=[O:11])[C:13](=[O:23])[NH:14][C@@H:15]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH3:16])=[O:31])[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1

Komponenten

6

Edukt 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 58979648(1-benzylcyclohexyl)methyl(1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)-5-[(4-morpholinylcarbonyl)amino]pentylcarbamate

Produkt 1

HCID 58979677(1-benzylcyclohexyl)methyl(1S)-5-[(4-morpholinylcarbonyl)amino]-1-(oxo{[(1R)-1-phenylethyl]amino}acetyl)pentylcarbamateAusbeute 82 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a −60° C. solution of 0.034 mL (0.39 mmol) of oxalyl chloride in 1 mL of dichloromethane was added 0.055 mL (0.78 mmol) of dimethylsulfoxide, dropwise. A solution of 110 mg (0.177 mmol) of (1-benzylcyclohexyl)methyl(1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)-5-[(4-morpholinylcarbonyl)amino]pentylcarbamate in 1 mL of dichloromethane was added dropwise and the reaction stirred for 10 min before 0.12 mL (0.89 mmol) of triethylamine was added dropwise. The reaction was let warm to room temperature and stirred for 15 min before being applied directly to a silica gel column eluting with 3:7 acetone:dichloromethane to afford 90 mg (82%) of (1-benzylcyclohexyl)methyl(1S)-5-[(4-morpholinylcarbonyl)amino]-1-(oxo{[(1R)-1-phenylethyl]amino}acetyl)pentylcarbamate. 1H NMR (300 MHz, 80° C., DMSO-d6) δ 8.91 (m, 1H), 7.15-7.38 (m, 11H), 6.30 (m, 1H) 5.01 (qnt, J=7 Hz, 1H), 4.85 (m, 1H), 3.63-3.72 (m, 2H), 3.54 (t, J=5 Hz, 4H), 3.26 (t, J=5 Hz, 4H), 3.04 (m, 2H), 2.66 (s, 2H), 1.316-1.714 (m, 19H). ES-LCMS m/z 643 (M+Na). HRMS C35H48N4O6 m/z 621.3652 (M+H)Cal; 621.3641 (M+Na)Obs.

Aufarbeitung

  1. additionwas added dropwise
  2. washeluting with 3:7 acetone

Quellen und Nachweise

ORD-Eintrag
ord-c795cbeec69e4316a0a1f715aad50b9b
Quelldatensatz
uspto-grants-2007_10
Patentnummer
US07282512B2

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