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CAS No. : | 277299-70-4 | MDL No. : | MFCD09795980 |
Formula : | C12H14N2O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | HBWBJCSXUJIDGN-UHFFFAOYSA-N |
M.W : | 202.25 | Pubchem ID : | 11735829 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With sodium bicarbonate; sodium acetate; In diethyl ether; acetic acid; | f 1-(3,4-Dimethylphenyl)-3-methyl-3-pyrazolin-5-one A solution of <strong>[60481-51-8]3,4-dimethylphenylhydrazine hydrochloride</strong> (17.7 g; 0.1 mol.), ethyl acetoacetate (13.0 g; 0.1 mol.) and sodium acetate (8.2 g; 0.1 mol.) in glacial acetic acid (250 mL) was stirred and heated under reflux for 24 h. The mixture was cooled and evaporated and the residue dissolved in diethyl ether (IL) and carefully washed with sat. aqu. sodium hydrogen carbonate (5*200 mL). The ethereal layer was evaporated to afford the title compound (15.4 g; 76percent). 1H NMR (300 MHz, d6-DMSO) delta11.30 (br s, 1H), 7.49 (d, J=1.4 Hz, 1H), 7.43 (dd, J=8.2 Hz, 1H), 7.14 (d, J=8.2 Hz, 1H), 5.31 (s, 1H), 2.20 (s, 3H), 2.22 (s, 3H), 2.08 (s, 3H); MS(ES) m/z 203 [M+H]. |
76% | With sodium acetate; In acetic acid; for 24h;Heating / reflux; | A solution of <strong>[60481-51-8]3,4-dimethylphenylhydrazine hydrochloride</strong> (17.7 g; 0.1 mol.), ethyl acetoacetate (13.0 g; 0.1 mol.) and sodium acetate (8.2 g; 0.1 mol.) in glacial acetic acid; (250 mL) was stirred and heated under reflux for 24 h. [0378] The mixture was cooled and evaporated and the residue dissolved in diethyl ether (1L) and carefully washed with sat. aqu. sodium hydrogen carbonate (5.x.200 mL). The ethereal layer was evaporated to afford the title compound (15.4 g; 76percent). 1H NMR (300 MHz, d6-DMSO) delta 11.30 (br s, 1H), 7.49 (d, J=1.4 Hz, 1H), 7.43 (dd, J=8.2 Hz, 1H), 7.14 (d, J=8.2 Hz, 1H), 5.31 (s, 1H), 2.20 (s, 3H), 2.22 (s, 3H), 2.08 (s, 3H); MS(ES) m/z 203 [M+H]. |
76% | With sodium acetate; acetic acid; for 24h;Reflux; | A solution of <strong>[60481-51-8]3,4-dimethylphenylhydrazine hydrochloride</strong> (17.7 g; 0.1 mol.), ethyl acetoacetate (13.0 g; 0.1 mol.) and sodium acetate (8.2 g; 0.1 mol.) in glacial acetic acid; (250 mL) was stirred and heated under reflux for 24h. The mixture was cooled and evaporated and the residue dissolved in diethyl ether (1L) and carefully washed with saturated aqueous sodium hydrogen carbonate (5 x 200 mL). The ethereal layer was evaporated to afford the title compound (15.4 g; 76percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | To a cooled at 0 to 10C mixture of 3'-Amino-2'-hydroxy-biphenyl-3-carboxylic acid (100 g) in methanol (2000 ml) was added aq. hydrochloric acid solution (150ml cone, hydrochloric acid in 150 ml water). Aq. sodium nitrite solution (31.87 g sodium nitrite in 100 ml water) was added to the reaction mixture at 0C to 10C within 15min and stirred further for lh. Triethylamine (200 ml) was added to the reaction mixture at 0C to 10C till pH 6 to 8 was obtained. 2-(3,4-dimethyl-phenyl)-5-methyl-l,2-dihydro-pyrazol-3-one (88.24 g) was added to the reaction mixture and stirred for 2h at 25C to 35C. After completion of the reaction on TLC, triethylamine (176.57g) was added to the reaction mixture and heated at 50C to 60C for 2h. The reaction mixture is distilled out under vacuum to get residue. Methanol (1000 ml) was added to the residue and heated at 50C to 60C for 30min. The reaction mixture was cooled to 25C to 35C for 2h. The suspension was filtered and obtained solid was washed with methanol (2 X 50 ml) to give wet cake. Water (1000 ml) was added to this wet cake and heated at 50C to 60C for lh. The reaction mixture is filtered, obtained solid was washed with water (2 X 50 ml) and suck dried to give wet cake. Water (1000 ml) was added to this wet cake and heated at 50C to 60C for lh. The reaction mixture was filtered, obtained solid was washed with water (2 X 50 ml) and suck dried. The solid was dried at 60C to 70C for 12- 15h to give eltrombopag triethylamine salt (180.0 g). Yield: 76.0%.Purity by HPLC: 99.6%. Eta NMR (DMSO) delta: 1.08-1.11 (9H, t), 2.19-2.33 (6H, m), 2.38 (3H,s), 2.87-2.92 (6H, q), 7.06- 7.13 (3H, t), 7.55-7.65 (2H, d), 7.74-7.89 (4H, d), 8.16-8.23(1H, d).Triethylamine content by titration: 18.5%.The XRPD of above obtained Eltrombopag triethylamine salt is given in fig 1 |
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