Hydrochloric Acid → 5-ethyl-N-[3-[3-(hydroxymethylidene)-2-oxo-1H-indole-6-carbonyl]phenyl]-1-methylpyrazole-3-carboxamide

HRID 641016Notes

Reaction equation

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

Participants

Conditions

Temperature: 78 °C

Procedure

5-Ethyl-1-methyl-1H-pyrazole-3-carboxylic acid [3-(2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amide (0.240 g, 0.6179 mmol) and ethyl formate (0.148 mL, 1.84 mmol) were dissolved in anhydrous ethanol (6 mL). The resulting solution was treated in dropwise fashion with a 21 wt % solution of sodium ethoxide in ethanol (1.2 mL, 3.21 mmol). This reaction mixture was heated at 78° C. for 0.5 h, producing a black oil. Subsequently, the reaction mixture was cooled to room temperature, and then the reaction pH was adjusted to pH 1 with dropwise addition of 1M HCl(aq) causing the formation of a tan precipitate. The suspension was filtered and the solids were washed with 0° C. EtOH to afford the pure 5-Ethyl-1-methyl-1H-pyrazole-3-carboxylic acid [3-(3-hydroxymethylene-2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amide (0.2187 g, 0.525 mmol, 85%).

Workup

customproducing a black oil
temperatureSubsequently, the reaction mixture was cooled to room temperature
filtrationThe suspension was filtered
washthe solids were washed with 0° C

Sources & evidence

ORD record: ord-3724ef6df0fd475a8c4fdd2c46cdfe1f
Source dataset: uspto-grants-2010_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07692005B2

Reaction notes

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