* 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.
General procedure: Into a 1L open reactor was added 500g of carboxylic acid raw material (chemically pure) and stirring was turned on (600 r/min) from the reactorThe bottom is continuously fed with ammonia gas (chemical purity, water content of 5.1percent by weight, flow rate of 100 g/min) to the carboxylic acid feed. After the reaction was allowed to proceed for TC hours at the reaction temperature TA, ammonia gas flow was stopped. The contents of the reactor were sampled and subjected to nuclear magnetic proton and elemental analysis to characterize the amide intermediate. Specific reaction conditions and characterization results are shown in Table A-1, Table A-2, Table A-3, Table A-4, Table A-5 and Table A-6. These characterization results show that the amide intermediates obtained have an extremely high purity (above 99percent).In this embodiment, the ammonia gas can be directly replaced with waste ammonia gas (from Yangzi Petrochemical Plant, containing approximately50wtpercent of ammonia gas, the rest were toluene, oxygen, nitrogen, steam, carbon monoxide, and carbon dioxide, and the flow rate of this waste ammonia was 130g/min).
7.6 g
With triethylamine; trifluoroacetic anhydride In tetrahydrofuran at 0 - 20℃; for 18 h;
To a solution of thiazole-4-carboxamide (10. Og, 67.1 mmol) in THF (150 mL) were slowly added triethylamine ( 42.1 mL, 302 mmol) and TFAA (19 mL, 134 mmol) at 0 °C successively. After being slowly warmed to rt and stirred for 18 hrs, the reaction mixture was diluted with H20 (100 mL) and extracted in DCM (50 mL) for three times. The combined organic phase was concentrated in vacuo and the residue was purified by column chromatography (eluting with PE/EA=5/1, v:v) to give thiazole-4-carbonitrile (7.6 g) as yellow oil.
Reference:
[1] Patent: CN104557357, 2018, B, . Location in patent: Paragraph 0150; 0151; 0152; 0162
[2] ACS Medicinal Chemistry Letters, 2014, vol. 5, # 6, p. 628 - 633
[3] Helvetica Chimica Acta, 1957, vol. 40, p. 554,558
[4] Bulletin de la Societe Chimique de France, 1969, p. 4026 - 4031
[5] Journal of the Chemical Society, 1960, p. 916 - 925
[6] Patent: WO2018/83081, 2018, A1, . Location in patent: Page/Page column 42; 43
[7] Patent: WO2007/138343, 2007, A1, . Location in patent: Page/Page column 7; 8
General procedure: Into a 1L open reactor was added 500g of carboxylic acid raw material (chemically pure) and stirring was turned on (600 r/min) from the reactorThe bottom is continuously fed with ammonia gas (chemical purity, water content of 5.1% by weight, flow rate of 100 g/min) to the carboxylic acid feed. After the reaction was allowed to proceed for TC hours at the reaction temperature TA, ammonia gas flow was stopped. The contents of the reactor were sampled and subjected to nuclear magnetic proton and elemental analysis to characterize the amide intermediate. Specific reaction conditions and characterization results are shown in Table A-1, Table A-2, Table A-3, Table A-4, Table A-5 and Table A-6. These characterization results show that the amide intermediates obtained have an extremely high purity (above 99%).In this embodiment, the ammonia gas can be directly replaced with waste ammonia gas (from Yangzi Petrochemical Plant, containing approximately50wt% of ammonia gas, the rest were toluene, oxygen, nitrogen, steam, carbon monoxide, and carbon dioxide, and the flow rate of this waste ammonia was 130g/min).
7.6 g
With triethylamine; trifluoroacetic anhydride; In tetrahydrofuran; at 0 - 20℃; for 18h;
To a solution of thiazole-4-carboxamide (10. Og, 67.1 mmol) in THF (150 mL) were slowly added triethylamine ( 42.1 mL, 302 mmol) and TFAA (19 mL, 134 mmol) at 0 C successively. After being slowly warmed to rt and stirred for 18 hrs, the reaction mixture was diluted with H20 (100 mL) and extracted in DCM (50 mL) for three times. The combined organic phase was concentrated in vacuo and the residue was purified by column chromatography (eluting with PE/EA=5/1, v:v) to give thiazole-4-carbonitrile (7.6 g) as yellow oil.
With triethylamine; trifluoroacetic anhydride; at -78 - 20℃;
Preparation of nitrile intermediates (Method A); The desired carboxylic acid (1 g) was refluxed in 10 ml of SOCI2 for 2h. SOCI2 was removed under reduced pressure. Dry toluene was added. The solution was cooled to O0C with ice bath. Ammonia was bubbled in toluene for 30 min. Solid was filtered and the filtrate was concentrated to obtain the crude amide which was used to next step without further purification.To a stirred mixture of amide (1.0 eq) and Et3N (4.5eq) was added dropwise (CF3CO)2theta (TFFA, 2 eq) at - 780C under N2. The mixture was stirred overnight at room temperature. Ice water was added to destroy TFAA. The mixture was extracted with CH2Cl2. The organic phases were combined, dried over Na2Stheta4 and concentrated to afford the product.
General procedure: Into a 1L open reactor was added 500g of carboxylic acid raw material (chemically pure) and stirring was turned on (600 r/min) from the reactorThe bottom is continuously fed with ammonia gas (chemical purity, water content of 5.1percent by weight, flow rate of 100 g/min) to the carboxylic acid feed. After the reaction was allowed to proceed for TC hours at the reaction temperature TA, ammonia gas flow was stopped. The contents of the reactor were sampled and subjected to nuclear magnetic proton and elemental analysis to characterize the amide intermediate. Specific reaction conditions and characterization results are shown in Table A-1, Table A-2, Table A-3, Table A-4, Table A-5 and Table A-6. These characterization results show that the amide intermediates obtained have an extremely high purity (above 99percent).In this embodiment, the ammonia gas can be directly replaced with waste ammonia gas (from Yangzi Petrochemical Plant, containing approximately50wtpercent of ammonia gas, the rest were toluene, oxygen, nitrogen, steam, carbon monoxide, and carbon dioxide, and the flow rate of this waste ammonia was 130g/min).
A mixture of thiazole-4-carboxylic acid (10.0 g, 77.4 mmol) and SOCl2 (100 mL) was stirred for 5 hrs at 60 °C. The resulting reaction mixture was then cooled and concentrated in vacuo and the residue was dissolved in THF (100 mL). To the solution was added ammonium hydroxide (18.1 mL, 465 mmol) slowly at 0 °C. The resulting mixture was stirred for one hour at rt, then diluted with water (100 mL) and extracted in DCM (50 mL) for three times. The combined organic layer was dried over anhydrous Na2S04 and concentrated in vacuo to give crude thiazole-4-carboxamide (10.3g) as yellow solid, which was used in the next step.