N,N'-Dimethylethylenediamine → N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)acetamide

HRID 705482Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 705482
[Cl:1][C:2]1[C:6]([NH:7][C:8](=[O:10])[CH3:9])=[CH:5][NH:4][N:3]=1.Br[C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1.IC1C=NC=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CNCCNC>[Cu]>[Cl:1][C:2]1[C:6]([NH:7][C:8](=[O:10])[CH3:9])=[CH:5][N:4]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[N:3]=1

Komponenten

7

Edukt 5

HCID 8070N,N'-DimethylethylenediamineHCID 122863-BromopyridineHCID 62657Potassium Phosphate, TribasicHCID 707143-IodopyridineHCID 178474372N-(3-chloro-1H-pyrazol-4-yl)acetamide

Produkt 1

HCID 118023019N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)acetamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 23978CopperKatalysator

Versuchsvorschrift

In step c of Scheme 1, N-(3-chloro-1H-pyrazol-4-yl)acetamide (1b) is reacted with a halopyridine such as 3-bromopyridine or 3-iodopyridine in the presence of a copper salt (such as copper(I) chloride (CuCl), copper(II) chloride (CuCl2), or copper(I) iodide (CuI)), potassium phosphate (K3PO4), and N,N′-dimethylethane-1,2-diamine to yield N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)acetamide (1c). It has been discovered that when copper(I) iodide is used that the yield of the reaction is greatly affected by the quality of the copper(I) iodide. The process may be conducted in a polar solvent, such as, acetonitrile (MeCN), dioxane, or N,N-dimethylformamide at a temperature between about 50° C. and about 110° C. It was surprisingly discovered that the addition of water during the work-up of this step maximizes the yield. Further, this synthetic method is simpler and reduces the costs of starting materials over known heteroarylation methods.

Quellen und Nachweise

ORD-Eintrag
ord-9a5e215d9d4740979c063d9f1c47c95b
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09174962B2

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