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

HRID 409394Notes

Reaction equation

HRID 409394 reaction equation
[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]

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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).

Workup

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

Sources & evidence

ORD record
ord-1a7719ca49814051b45e468c4f69d5c0
Source dataset
uspto-grants-2014_06
Patent number
US08759386B2

Reaction notes

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