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

HRID 251360

反応式

HRID 251360 の反応式
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]=COCC)[CH3:15].C(N(CC)CC)C>C(O)C>[CH2:14]([O:16][C:17]([C:18]1[CH:19]=[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]

参加物

5

反応物 3

HCID 8471Triethylamine2 回HCID 567775083-Hydrazino-4-methylbenzoic acid hydrochloride2 回HCID 86652221Ethyl(ethoxymethylene)cyanoacrylate

生成物 1

HCID 580890025-Amino-1-(5-carboxy-2-methyl-phenyl)-1H-pyrazole-4-carboxylic acid ethyl ester収率 68%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
65 °C

実験手順

To a stirred solution of 3-hydrazino-4-methylbenzoic acid hydrochloride (Example 3A, 478 mg, 2.36 mmol, 1.0 eq) in 20 mL of ethanol were added ethyl(ethoxymethylene)cyanoacrylate (399 mg, 2.36 mmol, 1.0 eq) and triethylamine (329 μL, 2.36 mmol, 1.0 eq) and the mixture was heated at 65° C. for 5 hrs. After standing at room temperature overnight, additional 3-hydrazino-4-methylbenzoic acid hydrochloride (159 mg, 0.78 mmol, 0.3 eq) and triethylamine (110 μL, 0.78 mmol, 0.3 eq) and heated for 2.5. The mixture was cooled to room temperature and concentrated. The crude residue was purified by flash chromatography on silica gel (gradient elution from 7/3 hexanes/EtOAc to 1/1 to elute byproducts followed by EtOAc and 9/1 EtOAc/MeOH to elute product) to provide the product as a brown solid (464 mg, 68%). HPLC (4 minute 10-95 gradient) tR 1.87 min; MS m/z 290.1 [M+H]+; 1H NMR (CD3OD), δ 8.08 (d, J=7.0 Hz, 1 H), 7.93 (s, 1 H), 7.76 (s, 1 H), 7.54 (d, J=8.0 Hz, 1 H), 4.29 (q, J=7.1 Hz, 2 H), 2.19 (s, 3 H), 1.35 (d, J=7.1 Hz, 3 H), ppm; 13C NMR (CD3OD), δ 166.5, 163.8, 150.4, 141.7, 139.9, 135.3, 130.8, 129.5, 128.6, 93.8, 58.8, 15.8, 12.9 ppm.

後処理

  1. temperatureThe mixture was cooled to room temperature
  2. concentrationconcentrated
  3. customThe crude residue was purified by flash chromatography on silica gel (gradient elution from 7/3 hexanes/EtOAc to 1/1 to elute byproducts followed by EtOAc and 9/1 EtOAc/MeOH to elute product)

出典と根拠

ORDレコード
ord-65718befb97e478fbdece0aa3ce7c5b2
出典データセット
uspto-grants-2011_01
特許番号
US07863314B2

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