ChemicalBook CAS DataBase List tasquinimod

tasquinimod synthesis

8synthesis methods

Product Name:tasquinimod
CAS Number:254964-60-8
Molecular formula:C20H17F3N2O4
Molecular Weight:406.36

22864-65-9

3-Quinolinecarboxylic acid, 1,2-dihydro-4-hydroxy-5-Methoxy-1-Methyl-2-oxo-

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254964-60-8

General procedure for Example 8 N-methyl-N-(4-trifluoromethylphenyl)-1,2-dihydro-4-hydroxy-5-methoxy-1-methyl-2-oxoquinoline-3-carboxamide (Method B): 1,2-dihydro-4-hydroxy-5-methoxy-1-methyl-2-oxoquinoline-3-carboxylic acid (8 g, 0.032 mol) and triethylamine ( 15.5 ml, 0.11 mol) were dissolved in 10 ml of dichloromethane and cooled to 0°C. Within 0.5 h, 150 ml of a dichloromethane solution of thionyl chloride (3.0 ml, 0.042 mol) was added dropwise to this solution while maintaining the temperature at 4°C. After the dropwise addition, stirring was continued at 4°C for 4 hours. After completion of the reaction, the reaction mixture was diluted with 10 ml of dichloromethane and washed sequentially with cold 1 M sulfuric acid and 1 M sodium hydroxide solution. The pH of the aqueous phase was adjusted to 8-8.5, clarified by filtration and acidified with hydrochloric acid to pH 4. Upon standing, a crystalline precipitate was formed, the precipitate was collected by filtration, washed with water and dried to afford the target product 4-hydroxy-5-methoxy-N,1-dimethyl-2-oxo-N-(4-(trifluoromethyl)phenyl)-1,2-dihydroquinoline-3-carboxamide (8.5 g, 65% yield). The product was structurally confirmed by 1H NMR and 13C NMR and analyzed by ESI MS/MS.

Methyl 4-hydroxy-5-Methoxy-1-Methyl-2-oxo-1,2-dihydroquinoline-3-carboxylate

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22864-65-9 Synthesis

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Yield: 99%

Reaction Conditions:

in octane for 2 h;Product distribution / selectivity;Reflux;Molecular sieve;

Steps:

4
A mixture of 11 (5.00 g, 18.9 mmol), N-methyl-p-trifluoromethylaniline (5.13 g, 28.4 mmol) and n-octane (200 mL) were refluxed in a Soxhlet extraction apparatus containing 4A molecular sieves (22.9 g) for 2 hours. After cooling the mixture the product was isolated as above to furnish 7.6 g (99 %) of 4-hydroxy-5-methoxy-N,l-dimethyl-2-oxo-N-[(4- trifluoromethyl)phenyl] - 1 ,2-dihydroquino line-3 -carboxamide (C) . ¹ H-NMR analysis on the isolated product revealed no impurities other than 1 mol% remaining ester 11. 1 H-NMR (CDCI3) 9.9 (s, 1H), 7.50 (bs, 4H), 7.46 (t, 1H), 6.94 (d, 1H), 6.70 (d, 1H), 4.06 (s, 3H), 3.54 (s, 3H), 3.48 (s, 3H). When the same reaction was performed by the traditional distillation from n-octane (Entry 26) during 2 hours according to prior art US patent No. 6,875,869 the product was isolated in 94 % yield and determined by 1H-NMR analysis to consist of a mixture of compound C (96 mol%) and the starting material 11 (4 mol%).

References:

ACTIVE BIOTECH AB;BOCK, Lillemor Maria;HOLMBERG, P?r Henning;JANSSON, Karl-Erik WO2012/4338, 2012, A1 Location in patent:Page/Page column 13; 16

22864-65-9 Synthesis

22864-65-9
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254964-60-8
117 suppliers
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References