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

HRID 2041057노트

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HRID 2041057 반응식
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]

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 46635Ethyl 2-cyano-3-ethoxy-2-butenoateHCID 567775083-Hydrazino-4-methylbenzoic acid hydrochloride

생성물 1

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

시약·촉매·용매 1

HCID 702Ethanol용매

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온도
65 °C

실험 절차

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]+

후처리

  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)

출처 및 근거

ORD 기록
ord-738b3a9cd4ad49f9b24a8a5f7265d3de
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08580838B2

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