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CAS No. : | 247037-82-7 | MDL No. : | MFCD18651714 |
Formula : | C4H6ClN3S | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | MOIIOZOJYWYXEP-UHFFFAOYSA-N |
M.W : | 163.63 | Pubchem ID : | 18679584 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | |
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 |
---|---|---|
66% | With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 60℃; for 4h;Inert atmosphere; | Step 1 (Synthesis of 177-4) (0846) Compound 177-1 (3.86 g, 26.36 mmol, 1.0 eq.), 177-2 (10.0 g, 26.36 mmol, 1.0 eq.), 177-3 (4.31 g, 26.36 mmol, 1.0 eq.) were dissolved in anhydrous DMF (100 mL), and at 20 C. was added NaHCO3 (8.86 g, 105.44 mmol, 4.00 eq). After the addition, the reaction mixture was swept with nitrogen for 3 times, the mixture was warmed to 60 C., and stirred for 4 hours. The reaction mixture was cooled to room temperature, and filtered. The filtrate was concentrated under reduced pressure. The residue was dissolved in EtOAc, washed with water (100 mL), and then extracted with EtOAc (100 mL) for 3 times. (0847) The organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatograph with an eluent system of DCM/MeOH=20/1, 10/1, to obtain 11 g product as yellow oil, yield: 66%. (0848) LCMS (ESI) m/z: 527.1 [M+H+]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 4-methyl-morpholine; In tetrahydrofuran; at 60℃; for 20h;Large scale; | Compound 4 (1140 g, 3 mol) and anhydrous THF(7.5 L) were added to a 30 L jacketed reaction flask and stirred. Compound 6 (566 g, 3.45 mol), Compound 7 (502 g,1.1 mol) and NMM (760 g, 7.5 mol) were added. The reaction was refluxed (60 C.) for 20 h. The content of the intermediate carboxylic acid was monitored by HPLC and the temperature was cooled to 5-10 C. The isobutyl chloroformate (492 g, 3.6 mol, dissolved in 500 mE THF) was added dropwise and reacted at 5-10 C. for 1 h. TEC and HPEC showed that the intermediate carboxylic acid of the reaction was reacted completely. The reaction was quenched by the addition of H20 (3 E), and extracted with EtOAc (9 E), and the organic solvent was washed once with H20 (3 E) and concentrated to give 2.2 kg of mother liquor. The mother liquor was dissolved in EtOAc (3 E), THF (500 mE) was added, n-heptane (about 9 E) was slowly added dropwise and the mixture was stirred at 15 C. overnight with a solid precipitated, and filtered to give a crude solid with a purity of 95%, De=85%. Recrystallization of the crude product:The solid was dissolved in THF/EtOAc (100 g in 500/500 mE) at 50 C., added dropwise with n-heptane (1 E) and stirred for 1 h, then gradually cooled to 25 C. and stirred overnight, filtered to give Compound 9A as a white solid (500 g, purity: 96%, De>96%, yield: 27%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27.1% | Compound 4 (1140 g, 3 mol) and anhydrous THF (7.5 L) were added to a 30 L reaction flask and stirred. Compound 5 (566 g, 3.45 mol), compound 6 (502 g, 1.1 mol) and N-methylmorpholine (760 g, 7.5 mol) were added. The reaction solution was refluxed (60 C.) for 20 hours, cooled to 5 C. to 10 C., added with isobutyl chloroformate (492 g, 3.6 mol, dissolved in 500 mL THF) dropwise, and reacted at 5 C. to 10 C. for 1 hour. After the intermediate carboxylic acid was completely reacted, the reaction was quenched by the addition of water (3 L). Ethyl acetate (9 L) was added for extraction and the organic phase was washed with water (3 L) once, concentrated to give a mother liquor of 2.2 kg. The mother liquid was dissolved in ethyl acetate (3 L), added with tetrahydrofuran (500 mL), slowly added dropwise within-heptane (about 9 L), and stirred at 15 C. overnight to precipitate a solid. The solid was recrystallized from tetrahydrofuran/ethyl acetate/n-heptane solvent system (5 mL/5 mL/10 mL/g) to obtain 500 g compound 8A, of which the purity reached 96%, ee value>96% and yield was 27.1%. |
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