Ethyl Acetate → (1-[4-[(5-fluoro-3-methylbenzofuran-2-carbonyl)amino]benzyl]-3,5-dimethyl-1H-pyrazol-4-yl)acetic acid methyl ester

HRID 409394노트

반응식

HRID 409394 반응식
[CH3:1][O:2][C:3](=[O:20])[CH2:4][C:5]1[C:6]([CH3:19])=[N:7][N:8]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[CH:14][CH:13]=2)[C:9]=1[CH3:10].C(N(C(C)C)CC)(C)C.[F:30][C:31]1[CH:32]=[CH:33][C:34]2[O:38][C:37]([C:39](O)=[O:40])=[C:36]([CH3:42])[C:35]=2[CH:43]=1.CCCP(O)(O)=O.C(OCC)(=O)C>ClCCl>[CH3:1][O:2][C:3](=[O:20])[CH2:4][C:5]1[C:6]([CH3:19])=[N:7][N:8]([CH2:11][C:12]2[CH:13]=[CH:14][C:15]([NH:18][C:39]([C:37]3[O:38][C:34]4[CH:33]=[CH:32][C:31]([F:30])=[CH:43][C:35]=4[C:36]=3[CH3:42])=[O:40])=[CH:16][CH:17]=2)[C:9]=1[CH3:10]

참가 물질

7

반응물 5

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 204484Propylphosphonic acidHCID 21447275-Fluoro-3-methylbenzofuran-2-carboxylic acidHCID 66707335[1-(4-aminobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl]acetic acid methyl ester

생성물 1

HCID 68276309(1-[4-[(5-fluoro-3-methylbenzofuran-2-carbonyl)amino]benzyl]-3,5-dimethyl-1H-pyrazol-4-yl)acetic acid methyl ester수율 62.5%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of [1-(4-aminobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl]acetic acid methyl ester (400 mg, 1.46 mmol) in 5 mL dichloromethane are added diisopropylethylamine (1.5 mL, 8.8 mmol) and 5-fluoro-3-methyl-1-benzofuran-2-carboxylic acid (369 mg, 1.9 mmol). After stiffing at room temperature for 10 minutes a 50% solution of 1-propylphosphonic acid cyclic anhydride in ethyl acetate (1.725 mL, 2.93 mmol) is added with cooling and the mixture is stirred at room temperature for 12 hours. The solvent is evaporated in vacuo and the residue is purified by MPLC (dichloromethane/methanol 98:2) to yield 410 mg of (1-{4-[(5-fluoro-3-methylbenzofuran-2-carbonyl)amino]benzyl}-3,5-dimethyl-1H-pyrazol-4-yl)acetic acid methyl ester (ESI mass spectrum: [M+H]+=450; TLC: Rf=0.56 (dichloromethane/methanol 95:5, silicagel 60 F254)). b) To a solution of (1-{4-[(5-fluoro-3-methylbenzofuran-2-carbonyl)amino]benzyl}-3,5-dimethyl-1H-pyrazol-4-yl)acetic acid methyl ester (410 mg, 0.91 mmol) in dioxane/water (10 mL/10 mL) is added 1 M NaOH (2.3 mL) and the mixture is stirred at room temperature for 24 hours. The mixture is diluted with water and acidified with hydrochloric acid (1 M, 3.25 mL). The precipitate is filtered, washed with water and dried to yield 338 mg of the title compound (ESI mass spectrum: [M+H]+=436; Retention time HPLC: 0.85 min (method D).

후처리

  1. temperaturewith cooling
  2. customThe solvent is evaporated in vacuo
  3. customthe residue is purified by MPLC (dichloromethane/methanol 98:2)

출처 및 근거

ORD 기록
ord-1a7719ca49814051b45e468c4f69d5c0
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759386B2

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