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CAS No. : | 618061-76-0 | MDL No. : | MFCD19440885 |
Formula : | C24H27ClFN4O6P | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | FNGRCLBEXKFSST-INIZCTEOSA-N |
M.W : | 552.92 | Pubchem ID : | 15606393 |
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 |
---|---|---|
69.8% | Stage #1: With 1,1'-carbonyldiimidazole In tetrahydrofuran at 40℃; for 0.5 h; Stage #2: at 30 - 40℃; for 2 h; |
Example 1 Diethyl [4-(3-Chloro-4-Fluoro-Phenylamino)-7-((S)-Tetrahydrofuran-3-Yloxy)-Quinazolin-6-Ylcarbamoyl]-Methyl}-Phosphonate 3.58 kg of 1,1-carbonyldiimidazole (22.16 mol) are placed in 12.8 litres of tetrahydrofuran and at 40° C. combined with 4.52 kg (22.16 mol) of diethylphosphonoacetic acid dissolved in 6.5 litres of tetrahydrofuran. The mixture is stirred for 30 minutes at 40° C. The resulting solution is referred to as solution A. 6.39 kg (17.05 mol) of N4-(3-chloro-4-fluoro-phenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diamine are placed in 26.5 litres of tetrahydrofuran and at 40° C. combined with solution A and stirred for 2 hours at 30° C. 64 litres of tert.-butylmethylether are added to the suspension and after cooling to 20° C. the precipitate is removed by centrifuging. It is washed with a mixture of 16 litres of tetrahydrofuran and 16 litres of tert. -butylmethylether and then with 32 litres of water and dried at 50° C. Yield: 6.58 kg (69.8percent) of white crystals, content: HPLC 99.1 Fl percent |
41.0 g | Stage #1: With 1,1'-carbonyldiimidazole In tetrahydrofuran at 40℃; for 1 h; Stage #2: at 30℃; for 2.4 h; |
To the suspension of 28.0 g of Ι, Γ-carbonyldiimidazole in 98.0 ml of THF at about 40 °C, a solution of 33.9 g of 2-(diethoxyphosphoryl)acetic acid in 50.6 ml of THF was added dropwise. The reaction mixture was stirred for 1 hour at about 40 °C and then added to the solution of 40.5 g of (5")-Λ^-(3-ΜθΓθ-4- fluorophenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diamine (prepared according to step b) in 168 ml of THF at about 40 °C dropwise. The reaction mixture was cooled down to about 30 °C and stirred for 2.4 h hours when 405.0 ml of MTBE was added dropwise. The reaction mixture was cooled down to about 20 °C and stirred for 1.5 hours. Crystals were filtered off, washed twice with 40.5 ml of THF/MTBE 1 : 1, once with 40.5 ml of water and dried at 50 °C/ 15 mbar for about 16 hours. 41.0 g of (5)-diethyl 2-(4-(3-chloro-4-fluorophenylamino)-7-(tetrahydrofuran- 3-yloxy)quinazolin-6-ylamino)-2-oxoethylphosphonate was obtained |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With 1,1'-carbonyldiimidazole In DMF (N,N-dimethyl-formamide) at 20℃; for 4 - 5 h; | 60.07 g of diethoxyphosphorylacetic acid are placed in 750 ml of N,N-dimethylformamide and at ambient temperature combined with 48.67 g of N,N'-carbonyldiimidazole. After the development of gas has ceased 90.00 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-6-amino-[(S)-(tetrahydrofuran-3-yl)oxy]-quinazoline are added and the reaction mixture is stirred for about 4-5 hours at ambient temperature until the reaction is complete. The reaction mixture is then heated gently in the water bath and 750 ml of water are added twice. The thick suspension is stirred overnight and the next morning another 350 ml of water are added. The suspension is cooled in the ice bath, stirred for one hour and suction filtered. The filter cake is washed again with 240 ml of N,N-dimethylformamide/water (1:2) and 240 ml of diisopropylether and dried at 40° C. in the circulating air dryer. Yield: 117.30 g of (88 percent of theory) Rf value: 0.37 (silica gel, methylene chloride/methanol=9:1) Mass spectrum (ESI+): m/z=553, 555 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66.2% | Stage #1: at 40℃; Stage #2: at 30 - 40℃; for 2 h; |
(1) To a three-necked reaction flask was added 350 mL of tetrahydrofuran, and the mixture was stirred and 54.3 g of 1,1-dicarbonylimidazole was added as a white suspension. The temperature was raised to 40 ° C, 57.1 g of diethylphosphonic acid was dissolved in tetrahydrofuran, and the mixture was added dropwise to the mixture at 40 ° C for 30 to 45 minutes. The above reaction mixture is solution A; (2) To a three-necked reaction flask was added 420 mL of tetrahydrofuran, stirred and stirred, and 84.0 g of compound 6, for the green solution. The temperature is raised to 40 ° C. The solution is B, and the solution A is added dropwise to the solution B, and the internal temperature is reduced to 30 ° C. (3) stirring for 2 hours, the reaction is complete. 420 mL of methyl tert-butyl ether was added and cooled to room temperature. After stirring for 30 minutes, the above white suspension was filtered. (4) was washed with 420 mL (tetrahydrofuran / methyl tert-butyl ether = 1: 1, by volume) The solid was washed with 1.7 L of water. Filter to dry. Dried to give 82.0 g of compound 8 in a yield of 66.2percent. |
[ 314771-88-5 ]
(S)-N-(3-Chloro-4-fluorophenyl)-6-nitro-7-((tetrahydrofuran-3-yl)oxy)quinazolin-4-amine
[ 162012-67-1 ]
N-(3-Chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine