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

HRID 705482Notes

Reaction equation

HRID 705482 reaction equation
[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

Participants

7

Reactant 5

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 23978CopperCatalyst

Procedure

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.

Sources & evidence

ORD record
ord-9a5e215d9d4740979c063d9f1c47c95b
Source dataset
uspto-grants-2015_11
Patent number
US09174962B2

Reaction notes

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