Hydrochloric Acid → HCID 136176942, compound

HRID 242213Notes

Reaction equation

[CH3:1][C:2]1[C:6]([C:7]2[C:8]([C:15]3[CH:20]=[CH:19][C:18]([O:21]C)=[CH:17][CH:16]=3)=[N:9][N:10]([CH3:14])[C:11]=2[CH:12]=[O:13])=[C:5]([CH3:23])[O:4][N:3]=1.Cl.NO.N1C=CC=CC=1.Cl>C(O)C.C(Cl)Cl>[CH3:1][C:2]1[C:6]([C:7]2[C:8]([C:15]3[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=3)=[N:9][N:10]([CH3:14])[C:11]=2[CH2:12][OH:13])=[C:5]([CH3:23])[O:4][N:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-(3,5-dimethylisoxazol-4-yl)-3-(4-methoxyphenyl)-1-methyl-1H-pyrazole-5-carbaldehyde (45.0 mg, 0.14 mmol), hydroxylamine hydrochloride (100 mg, 1.45 mmol) and pyridine (129 μL, 1.59 mmol) in ethanol (1 mL) was heated at 100° C. for 3 minutes in the microwave. 1 mL 2 M HCl and 5 mL DCM were added. A precipitate was formed, which was found to be the desired product. The remaining solution was extracted with DCM (5×3 mL). The DCM layer was filtered through a phase separator and concentrated together with the precipitate to give the raw product. To this was added thionyl chloride (3 mL) and the mixture was stirred at room temperature for 2 h and concentrated. Dry DCM (1 mL) and BF3.Me2S (1 M solution in DCM, 0.5 mL, 0.5 mmol) were added and stirred at room temperature over night. The mixture was concentrated and MeOH was added to quench the reaction The crude product was purified on silica gel to give 4-(3,5-dimethylisoxazol-4-yl)-3-(4-hydroxyphenyl)-1-methyl-1H-pyrazole-5-carbonitrile (30.5 mg, 0.01 mmol, 68%), and 3-(3-chloro-4-hydroxyphenyl)-4-(3,5-dimethylisoxazol-4-yl)-1-methyl-1H-pyrazole-5-carbonitrile (6.0 mg, 0.018 mmol, 13%).

Workup

customA precipitate was formed

Sources & evidence

ORD record: ord-8061cec413ab450b92828b14687a72f7
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653112B2

Reaction notes

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