Diethyl (ethoxymethylene)malonate → diethyl ({[1-(4-methoxybenzyl)-1H-pyrazol-5-yl]amino}methylidene)propanedioate
Reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:16]=[CH:15][C:7]([CH2:8][N:9]2[C:13]([NH2:14])=[CH:12][CH:11]=[N:10]2)=[CH:6][CH:5]=1.C(=O)(O)[O-].[Na+].[CH2:22]([O:24][C:25](=[O:36])[C:26](=[CH:32]OCC)[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH3:23]>>[CH2:22]([O:24][C:25](=[O:36])[C:26](=[CH:32][NH:14][C:13]1[N:9]([CH2:8][C:7]2[CH:6]=[CH:5][C:4]([O:3][CH3:2])=[CH:16][CH:15]=2)[N:10]=[CH:11][CH:12]=1)[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH3:23]Participants
4
Conditions
- Temperature
- 120 °C
Procedure
2-(4-Methoxybenzyl)-2H-pyrazol-3-ylamine hydrochloride (5.582 g) was neutralized with a saturated sodium bicarbonate solution, and the resulting mixture was extracted with ethyl acetate. To the obtained yellow oil, 2-ethoxymethylenemalonic acid diethyl ester (3.89 mL, 0.7 equivalents) was added. The mixture was stirred at 120° C., and 2-ethoxymethylenemalonic acid diethyl ester (about 1 equivalent in total) was further added thereto while stirring at 120° C. to consume the raw material. The reaction solution was purified by silica-gel column chromatography (ethyl acetate/hexane=2/1 to 3/0) to give 2-{[2-(4-methoxybenzyl)-2H-pyrazol-3-ylamino]methylene}malonic acid diethyl ester (5.420 g, yield: 53%) as a yellow oil.
Workup
- extractionthe resulting mixture was extracted with ethyl acetate
- stirringwhile stirring at 120° C.
- customto consume the raw material
- customThe reaction solution was purified by silica-gel column chromatography (ethyl acetate/hexane=2/1 to 3/0)
Sources & evidence
- ORD record
- ord-d820942bc6304d68902614cfb06d1181
- Source dataset
- uspto-grants-2012_10
- Patent number
- US08299252B2
Reaction notes
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