Thionyl Chloride → 4-Chloro-2-methyl-2H-pyrazole-3-carboxylic acid [3-(2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amide

HRID 2352885Notes

Reaction equation

[Cl:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]([OH:10])=O.S(Cl)(Cl)=O.[NH2:15][C:16]1[CH:17]=[C:18]([CH:31]=[CH:32][CH:33]=1)[C:19]([C:21]1[CH:29]=[C:28]2[C:24]([CH2:25][C:26](=[O:30])[NH:27]2)=[CH:23][CH:22]=1)=[O:20]>C1COCC1>[O:30]=[C:26]1[CH2:25][C:24]2[C:28](=[CH:29][C:21]([C:19]([C:18]3[CH:17]=[C:16]([NH:15][C:8]([C:3]4[N:4]([CH3:7])[N:5]=[CH:6][C:2]=4[Cl:1])=[O:10])[CH:33]=[CH:32][CH:31]=3)=[O:20])=[CH:22][CH:23]=2)[NH:27]1

Participants

Conditions

Temperature: 79 °C

Procedure

A dry 25 mL flask was charged with 4-Chloro-2-methyl-2H-pyrazole-3-carboxylic acid (0.139 g, 0.873 mmol) and thionyl chloride (5 mL) and allowed to stir at 79° C. for 2 h. The thionyl chloride was then removed by concentration in vacuo. The crude acid chloride was cooled to room temperature, and then dissolved in THF (5 mL). 6-(3-Amino-benzoyl)-1,3-dihydro-indol-2-one (as prepared in Example 40, 0.200 g, 0.794 mmol) was added to the THF solution of the acid chloride, and the mixture was allowed to reflux for 2 h. The reaction mixture was then allowed to cool to room temperature. The tan solids were filtered and washed with ˜3 mL of THF to afford the pure 4-Chloro-2-methyl-2H-pyrazole-3-carboxylic acid [3-(2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amide (0.264 g, 0.667 mmol, 84%).

Workup

customThe thionyl chloride was then removed by concentration in vacuo
temperatureThe crude acid chloride was cooled to room temperature
dissolutiondissolved in THF (5 mL)
temperatureto reflux for 2 h
temperatureto cool to room temperature
filtrationThe tan solids were filtered
washwashed with ˜3 mL of THF

Sources & evidence

ORD record: ord-debce0688290429495024d253bd1ac6f
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07749530B2

Reaction notes

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