Tert-butyl 2-acetyl-3-(dimethylamino)acrylate → tert-butyl 1-(4-chloropyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylate

HRID 1508337Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([N:8]2[C:12]([CH3:13])=[C:11]([C:14]([OH:16])=[O:15])[CH:10]=[N:9]2)[CH:3]=1.CN([CH:20]=[C:21]([C:29](=O)C)[C:22](OC(C)(C)C)=O)C>C(#N)C>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([N:8]2[C:12]([CH3:13])=[C:11]([C:14]([O:16][C:21]([CH3:29])([CH3:22])[CH3:20])=[O:15])[CH:10]=[N:9]2)[CH:3]=1

Participants

Conditions

Temperature: 85 °C

Procedure

1-(4-Chloropyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid: To a solution of tert-butyl 2-((dimethylamino)methylene)-3-oxobutanoate (0.032 g, 0.148 mmol) in acetonitrile (2 mL) was added TEA (0.021 mL, 0.148 mmol) and Intermediate 42A (0.024 g, 0.133 mmol). The dark brown solution was heated to 85° C. for 1 h. The reaction mixture was concentrated, and water (1 mL) and CH2Cl2 (1 mL) were added. The organic layer was concentrated and purified by silica gel chromatography to give tert-butyl 1-(4-chloropyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylate (12 mg, 27%) as yellow oil. MS(ESI) m/z: 294.2 (M+H)+. To the oil was added 4 N HCl in dioxane (2 mL). The reaction was stirred at rt for 4 h, and the clear orange solution was evaporated to dryness followed by coevaporation with toluene (2×) to give the desired product as sticky pink solid. MS(ESI) m/z: 238.2 (M+H)+.

Workup

concentrationThe reaction mixture was concentrated
additionwater (1 mL) and CH2Cl2 (1 mL) were added
concentrationThe organic layer was concentrated
custompurified by silica gel chromatography

Sources & evidence

ORD record: ord-f9d11d7ca0c34f2ba243cc1ad032999e
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09221818B2

Reaction notes

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