Hydrochloric Acid → (1-{4-[(5-Fluoro-3-methylbenzofuran-2-carbonyl)amino]benzyl}-3,5-dimethyl-1H-pyrazol-4-yl)acetic acid

HRID 409395ノート

反応式

HRID 409395 の反応式
C[O:2][C:3](=[O:33])[CH2:4][C:5]1[C:6]([CH3:32])=[N:7][N:8]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:19]([C:21]3[O:22][C:23]4[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:24]=4[C:25]=3[CH3:26])=[O:20])=[CH:14][CH:13]=2)[C:9]=1[CH3:10].[OH-].[Na+].Cl>O1CCOCC1.O.O>[F:31][C:28]1[CH:29]=[CH:30][C:23]2[O:22][C:21]([C:19]([NH:18][C:15]3[CH:16]=[CH:17][C:12]([CH2:11][N:8]4[C:9]([CH3:10])=[C:5]([CH2:4][C:3]([OH:33])=[O:2])[C:6]([CH3:32])=[N:7]4)=[CH:13][CH:14]=3)=[O:20])=[C:25]([CH3:26])[C:24]=2[CH:27]=1

参加物

6

反応物 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 68276309(1-[4-[(5-fluoro-3-methylbenzofuran-2-carbonyl)amino]benzyl]-3,5-dimethyl-1H-pyrazol-4-yl)acetic acid methyl ester

生成物 1

HCID 59054498(1-{4-[(5-Fluoro-3-methylbenzofuran-2-carbonyl)amino]benzyl}-3,5-dimethyl-1H-pyrazol-4-yl)acetic acid収率 85.3%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 218864351,4-Dioxane--water (1/1)溶媒

実験手順

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).

後処理

  1. filtrationThe precipitate is filtered
  2. washwashed with water
  3. customdried

出典と根拠

ORDレコード
ord-9bb543b326e04fa288dbbc25066006ea
出典データセット
uspto-grants-2014_06
特許番号
US08759386B2

反応ノート

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