P-Cresol → 6-Chloro-5-(4-methoxyphenyl)-1H-indazole-3-carboxylic acid p-tolyl ester

HRID 338480Notes

Reaction equation

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

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 6-chloro-5-(4-methoxyphenyl)-1H-indazole-3-carboxylic acid (547 mg, 1.81 mmol) in thionyl chloride (10 mL) was heated to 60° C. for 4 hours, cooled to room temperature and concentrated in vacuo. The residue was dissolved in CH2Cl2 (20 mL) and treated with p-cresol (399 mg, 3.61 mmol) followed by triethylamine (369 mg, 3.61 mmol). The reaction mixture was stirred for 16 hours and quenched with water (20 mL). The layers were separated and the organic phase was concentrated in vacuo. The residue was purified by flash chromatography (25-50% EtOAc/heptane) to give the title compound (192 mg, 27% yield).

Workup

temperaturecooled to room temperature
concentrationconcentrated in vacuo
dissolutionThe residue was dissolved in CH2Cl2 (20 mL)
customquenched with water (20 mL)
customThe layers were separated
concentrationthe organic phase was concentrated in vacuo
customThe residue was purified by flash chromatography (25-50% EtOAc/heptane)

Sources & evidence

ORD record: ord-61649f6597364da7970a7b1158d31365
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889730B2

Reaction notes

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