Triethylamine → 5-Amino-1-(5-carboxy-2-methyl-phenyl)-3-methyl-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 884798

Reaction equation

Cl.[NH:2]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]=1[CH3:13])[C:7]([OH:9])=[O:8])[NH2:3].[CH2:14]([O:16][C:17](=[O:26])[C:18]([C:24]#[N:25])=[C:19](OCC)[CH3:20])[CH3:15].C(N(CC)CC)C>C(O)C>[CH2:14]([O:16][C:17]([C:18]1[C:19]([CH3:20])=[N:3][N:2]([C:4]2[CH:5]=[C:6]([C:7]([OH:9])=[O:8])[CH:10]=[CH:11][C:12]=2[CH3:13])[C:24]=1[NH2:25])=[O:26])[CH3:15]

Participants

Conditions

Temperature: 65 °C

Procedure

To a stirred solution of 3-hydrazino-4-methylbenzoic acid hydrochloride (Example 3A, 353 mg, 1.74 mmol, 1.0 eq) in 15 mL of ethanol were added 2-cyano-3-ethoxy-but-2-enoic acid ethyl ester (prepared as described by Xia et al., J. Med. Chem., 1997, 40, 4372) (319 mg, 1.746 mmol, 1.0 eq) and triethylamine (242 μL, 1.74 mmol, 1.0 eq) and the mixture was heated at 65° C. overnight. The mixture was cooled to room temperature and concentrated. The crude residue was purified by flash chromatography on silica gel (loaded with CH2Cl2, and packed and eluted with gradient from 6/4 hexanes/EtOAc to elute byproducts followed by 8/2 EtOAc/hexanes and 8/2 EtOAc/MeOH to elute product) to provide the product as a brown solid (464 mg, 68%). HPLC (4 minute 10-95 gradient) tR 1.97 min; MS m/z 304.1 [M+H]+

Workup

temperatureThe mixture was cooled to room temperature
concentrationconcentrated
customThe crude residue was purified by flash chromatography on silica gel (loaded with CH2Cl2, and packed and eluted with gradient from 6/4 hexanes/EtOAc to elute byproducts followed by 8/2 EtOAc/hexanes and 8/2 EtOAc/MeOH to elute product)

Sources & evidence

ORD record: ord-5adbb5607bb14ab3aa30c214ba78db5f
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08242117B2

Linked notes

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