三乙胺 → 5-Amino-1-(5-carboxy-2-methyl-phenyl)-3-methyl-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 251362

反应方程式

HRID 251362 反应方程式
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]

参与物

5

反应物 3

HCID 8471三乙胺HCID 46635Ethyl 2-cyano-3-ethoxy-2-butenoateHCID 567775083-肼基-4-甲基苯甲酸盐酸盐

产物 1

HCID 670242365-Amino-1-(5-carboxy-2-methyl-phenyl)-3-methyl-1H-pyrazole-4-carboxylic acid ethyl ester收率 87.9%

试剂、催化剂与溶剂 1

HCID 702乙醇溶剂

反应条件

温度
65 °C

实验过程

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]+

后处理

  1. temperatureThe mixture was cooled to room temperature
  2. concentrationconcentrated
  3. 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)

来源与证据

ORD记录
ord-350dac818c464c3aab80db5292781355
来源数据集
uspto-grants-2011_01
专利号
US07863314B2

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