Ethyl Bromide → N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethylacetamide

HRID 1484590Notes

Reaction equation

HRID 1484590 reaction equation
[Cl:1][C:2]1[C:6]([NH:7][C:8](=[O:10])[CH3:9])=[CH:5][N:4]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[N:3]=1.[CH2:17](Br)[CH3:18].[H-].[Na+].CC(C)([O-])C.[Na+]>O1CCCC1>[Cl:1][C:2]1[C:6]([N:7]([CH2:17][CH3:18])[C:8](=[O:10])[CH3:9])=[CH:5][N:4]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[N:3]=1

Participants

6

Reactant 4

HCID 6332Ethyl BromideHCID 24758Sodium hydrideHCID 23676156Sodium t-butoxideHCID 118023019N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)acetamide

Product 1

HCID 72194633N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethylacetamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In step 2d, N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)acetamide (2-8) is alkylated with ethyl bromide (EtBr) in the presence of a base, such as sodium hydride (NaH) or sodium tert-butoxide (NaOt-Bu), in a polar aprotic solvent, such as tetrahydrofuran, at temperatures from about 20° C. to about 40° C., over a period of time of about 60 hours to about 168 hours, to yield N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethylacetamide (2-9). It has been discovered that use of an iodide additive, such as potassium iodide (KI) or tetrabutylammonium iodide (TBAI) can decrease the time necessary for the reaction to occur to about 24 hours. It has also been discovered that heating the reaction at about 50° C. to about 70° C. in a sealed reactor (to prevent loss of ethyl bromide) also decreases the reaction time to about 24 hours.

Sources & evidence

ORD record
ord-ad13099dac8f4cf9b3e5f4ccd5150e3c
Source dataset
uspto-grants-2016_08
Patent number
US09422265B2

Reaction notes

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