Diisopropylethylamine → N-{(1S,2R)-1-(3,5-Difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-{[(2-hydroxyethyl)(propyl)amino]methyl}benzamide Dihydrochloride

HRID 348896Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 348896
[OH:1][CH2:2][CH2:3][N:4]([CH2:8][C:9]1[CH:10]=[C:11]([CH:16]=[CH:17][CH:18]=1)[C:12]([O:14]C)=O)[CH2:5][CH2:6][CH3:7].O.[OH-].[Li+].[ClH:22].Cl.[NH2:24][C@@H:25]([CH2:38][C:39]1[CH:44]=[C:43]([F:45])[CH:42]=[C:41]([F:46])[CH:40]=1)[C@H:26]([OH:37])[CH2:27][NH:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([I:36])[CH:31]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>O1CCCC1.CO.O>[ClH:22].[ClH:22].[F:45][C:43]1[CH:44]=[C:39]([CH:40]=[C:41]([F:46])[CH:42]=1)[CH2:38][C@H:25]([NH:24][C:12](=[O:14])[C:11]1[CH:16]=[CH:17][CH:18]=[C:9]([CH2:8][N:4]([CH2:3][CH2:2][OH:1])[CH2:5][CH2:6][CH3:7])[CH:10]=1)[C@H:26]([OH:37])[CH2:27][NH:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([I:36])[CH:31]=1

Komponenten

7

Edukt 5

HCID 81531DiisopropylethylamineHCID 168937Lithium hydroxide, monohydrateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21086147Methyl 3-{[(2-hydroxyethyl)(propyl)amino]methyl}benzoateHCID 57487297HCID 57487297, Verbindung

Produkt 1

HCID 68608663N-{(1S,2R)-1-(3,5-Difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-{[(2-hydroxyethyl)(propyl)amino]methyl}benzamide Dihydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 21892291Methanol tetrahydrofuran waterLösungsmittel

Versuchsvorschrift

Methyl 3-{[(2-hydroxyethyl)(propyl)amino]methyl}benzoate (500 mg, 2 mmol) and lithium hydroxide monohydrate (170 mg, 4 mmol) are stirred in 2:1:1 tetrahydrofuran/methanol/water (4 mL) at room temperature for 16 h. The reaction is concentrated under reduced pressure and redissolved in DMF (15 mL). To this solution is added (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-iodobenzyl)amino]butan-2-ol dihydrochloride (1 g, 2 mmol), diisopropylethylamine (1.4 mL, 8 mmol), then HATU (1.1 g, 3 mmol), and the reaction stirred 2 h. Purification by flash column chromatography (silica, 10% methanol/chloroform) provides the title compound as the free base. The residue is dissolved in diethyl ether (5 mL) and 1N hydrochloric acid in diethyl ether (3 mL) is added. The mixture is concentrated under reduced pressure to yield the title compound. ESI MS m/z 652.2 [M+H]+.

Aufarbeitung

  1. concentrationThe reaction is concentrated under reduced pressure
  2. dissolutionredissolved in DMF (15 mL)
  3. customPurification by flash column chromatography (silica, 10% methanol/chloroform)

Quellen und Nachweise

ORD-Eintrag
ord-53a61d60974346d4a5637e1106704198
Quelldatensatz
uspto-grants-2007_02
Patentnummer
US07176242B2

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