N-(-1-hydrogen-inden-1-yl)sulfonamide compounds and their preparation methods and uses
A compound, C1-C12 technology, applied in the field of medicine to achieve the effect of avoiding poor selectivity, strong targeting, and good therapeutic potential
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Embodiment 1
[0142] Example 1: 2-(1-(4-fluorobenzenesulfonamido)-1-hydrogen-inden-4-yl)acetic acid (A001) (prepared according to Reaction Scheme 1)
[0143] 1.1 Preparation of 3-(2-(bromomethyl)phenyl)methyl acrylate
[0144] Add 2.97g of iodobenzyl bromide, 1.72g of methyl acrylate, 225mg of palladium acetate, 2.78g of tetrabutylammonium chloride, 4.14g of potassium carbonate and 50mL of anhydrous DMF into a 250mL reaction flask, nitrogen replacement 3 times, and stir at room temperature overnight. The reaction solution was poured into water, extracted 3 times with ethyl acetate, combined the organic phases, washed 2 times with 0.1N HCl and 2 times with saturated brine, dried, filtered, spin-dried the solvent, and purified by column chromatography to obtain 2.1 g of Yellow oil.
[0145] 1 HNMR (CDCl 3 ,400MHz):δ8.07(d,J=16.0Hz,1H),7.67-7.56(m,1H),7.42-7.31(m,3H),6.45(d,J=16.0Hz,1H),4.60( s,2H),3.84(s,3H).ESI-MSm / z:256[M+H] + .
[0146] 1. Preparation of 24-bromomethyl-1-hydrogen-1-...
Embodiment 2
[0158] Example 2: 2-(1-(4-fluorobenzenesulfonamido)-1-hydrogen-inden-4-yl)-3-oxobutanoic acid (A015) (prepared according to the reaction scheme 2)
[0159] Dissolve 3.6g of compound A001 in THF, add EDCI to react for 2 hours, then add 1.1 equivalent of methyl malonate monopotassium salt, after reacting for 10 hours, add 2N NaOH aqueous solution, after reacting at room temperature for 2 hours, the reaction solution Adjusted to neutral, extracted with ethyl acetate, washed with saturated brine, dried, spin-dried, and purified by column chromatography to obtain an off-white solid.
[0160] 1 HNMR(d 6 -DMSO,400MHz):δ12.34(br,1H),7.96-7.87(m,2H),7.42-7.10(m,6H),6.53(d,J=2.4Hz,1H),6.33(d,J =2.4Hz,1H),4.69(s,2H),3.45-3.37(m,4H).ESI-MSm / z:412[M+Na] + .
Embodiment 3
[0161] Example 3: 2-(2-(1-(4-fluorobenzenesulfonyl)-hydrogen-inden-4-yl)acetamido)acetic acid (A029) (prepared according to Reaction Scheme 3)
[0162] 3.1 Preparation of ethyl 2-(2-(1-(4-fluorobenzenesulfonyl)-hydrogen-inden-4-yl)acetamido)acetate
[0163] Add 3.6g of compound A001, 1.37g of glycine methyl ester hydrochloride, 1.1 equivalents of TBTU, 1.1 equivalents of triethylamine and 40mL of DCM into the reaction flask, react at room temperature for 2 hours, wash 3 times with 0.1N HCl, and wash 2 times with saturated saline , dried, filtered, and spin-dried to obtain a crude product. used directly in the next step.
[0164] ESI-MSm / z:455[M+Na] + .
[0165] 3.2 Preparation of 2-(2-(1-(4-fluorobenzenesulfonyl)-hydrogen-inden-4-yl)acetamido)acetic acid
[0166] The product from the previous step was dissolved in 40 mL THF, 40 mL 2N NaOH aqueous solution was added, and vigorously stirred for 2 hours. The reaction solution was adjusted to neutrality, extracted, dried, and...
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