Phenylacetyl chloride → N-{(3R*,4S*)-1-Benzyl4-[(isopropyl-phenylacetyl-amino)-methyl]-pyrrolidin-3-ylmethyl}-N-isopropyl-4-methoxy-3-(3-methoxy-propoxy)-benzamide

HRID 1158486Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1158486
[CH2:1]([N:8]1[CH2:12][C@@H:11]([CH2:13][NH:14][CH:15]([CH3:17])[CH3:16])[C@@H:10]([CH2:18][N:19]([CH:36]([CH3:38])[CH3:37])[C:20](=[O:35])[C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[C:23]([O:29][CH2:30][CH2:31][CH2:32][O:33][CH3:34])[CH:22]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:46]1([CH2:52][C:53](Cl)=[O:54])[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.[OH-].[Na+]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH2:1]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:15]([CH3:17])[CH3:16])[C:53](=[O:54])[CH2:52][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C@@H:10]([CH2:18][N:19]([CH:36]([CH3:38])[CH3:37])[C:20](=[O:35])[C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[C:23]([O:29][CH2:30][CH2:31][CH2:32][O:33][CH3:34])[CH:22]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

7

Edukt 4

HCID 7679Phenylacetyl chlorideHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 59512319N-[(3R*,4R*)-1-Benzyl-4-(isopropylamino-methyl)-pyrrolidin-3-ylmethyl]-N-isopropyl-4-methoxy-3-(3-methoxy-propoxy)-benzamide

Produkt 1

HCID 59512431N-{(3R*,4S*)-1-Benzyl4-[(isopropyl-phenylacetyl-amino)-methyl]-pyrrolidin-3-ylmethyl}-N-isopropyl-4-methoxy-3-(3-methoxy-propoxy)-benzamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a solution of N-[(3R*,4R*)-1-benzyl-4-(isopropylamino-methyl)-pyrrolidin-3-ylmethyl]-N-isopropyl-4-methoxy-3-(3-methoxy-propoxy)-benzamide (0.19 g, 0.36 mmol), triethyl-amine (0.15 mL, 1.09 mmol), and DMAP (0.013 g, 0.11 mmol) in CH2Cl2, is added dropwise phenyl-acetyl chloride (0.058 mL, 0.44 mmol) at 0° C. under a nitrogen atmosphere. The solution is stirred overnight at room temperature. The mixture is added an aqueous solution of NaOH 0.1N (50 mL) and CH2Cl2 (50 mL). The organic layer is separated and the aqueous phase extracted twice with CH2Cl2, dried over MgSO4, filtered, and concentrated in vacuo. The crude product is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 90:10) to give the title product. TLC, Rf (CH2Cl2/MeOH 9:1)=0.23. MS (LC-MS): [M+H]+; 644.4 tR (HPLC, C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/2.5 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 mL/min): 5.95 min.

Aufarbeitung

  1. customThe organic layer is separated
  2. extractionthe aqueous phase extracted twice with CH2Cl2
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 90:10)

Quellen und Nachweise

ORD-Eintrag
ord-a3a44da3faab43cdba812024fbb28899
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07807709B2

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