Category: 1174321-06-2

Synthetic Route of 1174321-06-2, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 1174321-06-2, name is 5-(Difluoromethyl)pyrazine-2-carboxylic acid belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

5-(Difluoromethyl)pyrazine2carboxylic acid (30.0 g, 1.05 equiv) and (4aS,5S,7aS)-7a-(5-amino-2-fluorophenyl)-5-fluoromethyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine (49.2 g, 1.00 equiv.) were charged to a reactor and EtOAc (443 mL) was added to the mixture to give a suspension. A solution of T3P (105 g 1.10 equiv, 50 wt% in EtOAc) (Archimica, Germany) was added at ambient temperature while controlling the internal temperature below 30 C. The reaction mixture was stirred at 4045 C >3 hours and monitored by HPLC. The reaction mixture was cooled to ambient temperature and water (98 mL) was charged. After 1015 minutes charged 28% ammonium hydroxide (137 mL) while controlling the temperature below 30 C. Additional EtOAc (172 mL) was added and the reaction mixture was stirred for 30 minutes at ambient temperature. The aqueous phase was separated and backextracted with EtOAc (246 mL). The organic phases were combined and washed with 15% aq. NaCl (98 mL) and water (98mL). The organic layer was filtered over Celite (0.5 Wt) and concentrated under vacuum to obtain a beige solid (quantitative crude yield) which was recrystallized from 1propanol to afford N-(3-((4aS,5S,7aS)-2-amino-5-(fluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-7a-yl)-4-fluorophenyl)-5-(difluoromethyl)pyrazine-2-carboxamide as a tan solid (54.2g).

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, 5-(Difluoromethyl)pyrazine-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ???????????????????????????; ? Buranko; Kimu ?; Chan ?; ?; Yoshizawa Kazuhiro; (94 pag.)JP2016/121177; (2016); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 1174321-06-2, name is 5-(Difluoromethyl)pyrazine-2-carboxylic acid, molecular formula is C6H4F2N2O2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. category: Pyrazines

5-(Difluoromethyl)pyrazine-2-carboxylic acid 42 (0.68 wt, 1.1 eq) was charged into a reactor and if needed, dried by azeotropic distillation with toluene. DMI (2.0V) was added and the mixture was cooled down to 0-5 C. Thionyl chloride (0.337 V, 1.30 eq) was added while keeping the internal T below 10 C. The resulting solution was stirred at 4-10 C until the conversion was >95.0 % by HPLC. The mixture was cooled down to 0 C and a solution of 39 (1.0 Wt, 1.0 eq) in DMI (2.5V) was charged while keeping the internal temperature below 5 C. The vessel was rinsed with DMI (0.50V) and the reaction mixture was stirred until the conversion is >99%. Water (12V) was charged and the resulting mixture is stirred at 15-20 C for 0.5h. EtOAc (15V) and then 50% aq. NaOH (1.5 Wt, 5.3 eq) were added while keeping T below 30 C. pH was monitored to make sure that it is above 10. The aqueous phase was separated and extracted with EtOAc (5.0V). Theorganic layers were combined and washed with brine (5.0V) and water twice (5.0V each). The mixture was filtered through a Celite pad (0.50 Wt) rinsing with EtOAc (3.0V). The filtrate was concentrated under reduced pressure at 40-50 C. 1-Propanol (15V) was charged and the mixture was warmed up to 90-100 C while stirring until a clear solution was obtained. The mixture was cooled down to 0-5 C over 2h and stired over lh. The mixture was filtered, rinsing with cold 1-propanol twice (2.5V each). Drying in an oven vacuum at 45 C overnight provided the title compound 43 as an off-white solid in 81% isolated yield.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1174321-06-2, its application will become more common.

Reference:
Patent; ???????????????????????????; ? Buranko; Kimu ?; Chan ?; ?; Yoshizawa Kazuhiro; (94 pag.)JP2016/121177; (2016); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 1174321-06-2, A common heterocyclic compound, 1174321-06-2, name is 5-(Difluoromethyl)pyrazine-2-carboxylic acid, molecular formula is C6H4F2N2O2, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

Example 140 N-(3-((6S,7R)-9-amino-6-fluoro-7-methyl-5,5-dioxido-5-thia-8-azaspiro[3.5]non-8-en-7-yl)-4-fluorophenyl)-5-(difluoromethyl)pyrazine-2-carboxamide As described in the HATU coupling procedure, tert-butyl ((6S,7R)-7-(5-amino-2-fluorophenyl)-6-fluoro-7-methyl-5,5-dioxido-5-thia-8-azaspiro[3.5]non-8-en-9-yl)carbamate (127 mg, 0.296 mmol) and 5-(difluoromethyl)pyrazine-2-carboxylic acid (61.8 mg, 0.355 mmol) were combined to provide the title compound (120 mg, 0.205 mmol, 69.3% yield) as an off-white solid. LC/MS (ESI+) m/z=486 (M+H). 1H NMR (400 MHz, DMSO-d6) ppm 10.91 (s, 1H) 9.37-9.39 (m, 1H) 9.08-9.10 (m, 1H) 7.81-7.89 (m, 2H) 7.11-7.42 (m, 2H) 6.59 (br. s., 2H) 5.92 (d, J=1.00 Hz, 1H) 2.58-2.82 (m, 4H) 1.94-2.27 (m, 2H) 1.62 (d, J=3.52 Hz, 3H)

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; LEWIS, Richard T.; ALLEN, Jennifer R.; CHENG, Yuan; CHOQUETTE, Deborah; EPSTEIN, Oleg; GUZMAN-PEREZ, Angel; HARRINGTON, Paul E.; HUA, Zihao; HUNGATE, Randall W.; HUMAN, Jason Brooks; JUDD, Ted; LIU, Qingyian; LOPEZ, Patricia; MINATTI, Ana Elena; OLIVIERI, Philip; ROMERO, Karina; RUMFELT, Shannon; RZASA, Robert M.; SCHENKEL, Laurie; STELLWAGEN, John; WHITE, Ryan; XUE, Qiufen; ZHENG, Xiao; ZHONG, Wenge; US2014/107109; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 1174321-06-2, name is 5-(Difluoromethyl)pyrazine-2-carboxylic acid, belongs to pyrazines compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 1174321-06-2, Safety of 5-(Difluoromethyl)pyrazine-2-carboxylic acid

Step 9: tert- Butyl ((4aS,5SJaS)-7a-(5-(5-(difluoromethyl)pyrazine-2-carboxamido)-2- fluorophenyl)-3-methyl-4-oxo-5-(trifluoromethyl)-3,4,4a,5J,7a-hexahydrofuror3,4- dlpyrimidin-2-yl)carbamate N- Ethyl-N-(propan-2-yl)propan-2- amine (300 muL, 1.7 mmol) was added to a stirred mixture of tert-butyl ((4aS,5S,7aS)-7a-(5-amino-2-fluorophenyl)-3-methyl-4-oxo-5- (trifluoromethyl)-3,4,4a,5,7,7a-hexahydrofuro[3,4-d]pyrimidin-2-yl)carbamate amine (150 mg, 0.34 mmol), 5-(difluoromethyl)pyrazine-2-carboxylic acid (90 mg, 0.50 mmol) and (lH-benzotriazol-l-yloxy)(tripyrrolidin-l-yl)phosphoniumhexafluorophosphate (265 mg, 0.50 mmol) in dry DCM (2 mL) at RT under nitrogen. The reaction was stirred at this temperature for 16 h, then partitioned between DCM and NaHCO3 (aq). The aqueous layer was extracted with DCM (x2). The combined extracts were dried by passing through a hydrophobic frit and then evaporated. The residue was purified by column chromatography (normal phase, 25 g, Biotage SNAP cartridge KP-SiI, 25mL per min, gradient 5% to 30% EtOAc in n-hexane) to give the title compound (92 mg, light yellow solid). 1H NMR (400 MHz, CDCl3) delta ppm 1.58 (s, 9H) 3.36 (s, 3H) 4.06 (d, J=7.83 Hz, IH) 4.40 (d, J=9.85 Hz, IH) 4.50 (dd, J=9.73, 2.91 Hz, IH) 4.57 – 4.65 (m, IH) 6.81 (t, J=54.60 Hz, IH) 7.22 (dd, J=10.86, 9.09 Hz, IH) 7.74 (dd, J=6.69, 2.65 Hz, IH) 7.84 (ddd, J=8.84, 4.17, 2.65 Hz, IH) 8.93 (s, IH) 9.52 (s, IH) 9.65 (s, IH) 10.64 (s, IH)

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; EISAI R&D MANAGEMENT CO., LTD; CASTRO PINEIRO, Jose, Luis; HALL, Adrian; MADIN, Andrew; VO, Ngoc-Tri; WO2011/9897; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 1174321-06-2, These common heterocyclic compound, 1174321-06-2, name is 5-(Difluoromethyl)pyrazine-2-carboxylic acid, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

To a stirred solution of tert-butyl 4-aminopiperazine-l-carboxylate (578 mg, 2.8 mmol, 1.0 equiv) in DMF (05 mL) was added HATU (2128 mg, 5.6 mmol, 2.0 equiv) at RT and stirred for 10 minutes. Then 5-(difluoromethyl)pyrazine-2-carboxylic acid (500 mg, 2.8 mmol, 1.0 equiv) was added followed by the addition of DIPEA (1.5 mL, 8.4 mmol, 3.0 equiv). The resulting reaction mixture was allowed to stir at RT for ovemigiit. Product formation was confirmed by LCMS. the reaction mixture was diluted with water (50 mL) and extracted with EtOAc (50 mL c 2). The combined organic layer was washed with water (30mL), brine solution (30 mL x 2), dried over anhydrous sodium sulfate and concentrated under reduced pressure, to obtain tert-butyl 4-(5-(difluoromethyl)pyrazine-2-carboxamido)piperazine-l -carboxylate (400 mg, 39 % Yield) as a brown solid. LCMS 358.2 [ M i l : NMR (400 MHz, DMSCWe) d 10.13 (s, 1 H), 9.24 (s, 1 H), 8.99 is. 1 H), 3.34 – 3.49 (m, 4 H), 2.84 (t, .7=5.04 Hz, 4 H), 1.41 (s, 9H).

The synthetic route of 1174321-06-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PRAXIS BIOTECH LLC; DELGADO OYARZO, Luz Marina; URETA DIAZ, Gonzalo Andres; PUJALA, Brahmam; PANPATIL, Dayanand; BERNALES, Sebastian; CHAKRAVARTY, Sarvajit; (0 pag.)WO2019/236710; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 1174321-06-2, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 1174321-06-2, name is 5-(Difluoromethyl)pyrazine-2-carboxylic acid belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

General Procedure A: the coupling of anilines prepared in Preparation Examples 25- (14) and 26-Q2) with aryl carboxylic acidsThe aniline (100 mg) was dissolved in DCM (2 mL) and the aryl carboxylic acid (1.2 – 1.6 equiv.), N,N-diisopropylethylamine (3 equiv.) and (lH-benzotriazol-1- yloxy)tripyrrolidin-l-yl)phosphonium hexafluorophophate (1.2 – 1.6 equiv.) were added. The reaction mixture was stirred at RT for 16 h – 3 days, and sodium bicarbonate (sat., aq., 25 mL) was added. The mixture was extracted with EtOAc (2 x40 mL), the combined organic portions were dried over MgSO4, evaporated and purified by silica gel chromatography (EtOAc/hexanes gradient) to afford the amide as a white solid. The amide was dissolved in DCM (2 mL) and TFA (1 mL) was added. After stirring at RT for 1-3 h, the reaction mixture was evaporated and sodium bicarbonate (sat., aq., 25 mL) was added. The mixture was extracted with EtOAc (2 x 40 mL), and the combined organic portions dried over MgSO4 and evaporated to afford the desired compound as a white solid. On occasions where the product was not pure, purification was effected by silica gel chromatography (MeOH/EtOAc/DCM gradients). Example 1 : N-(3-((‘4aR,5S,7aS)-2-amino-5-(‘fluoromethyl)-4a,5,7,7a-tetrahvdro-4H- furor3,4-diri,31oxazin-7a-yl)-4-fluorophenyl)-5-(difluoromethyl)pyrazine-2- carboxamideSynthesized from tert-butyl [(4aR,5S,7aS)-7a-(5-amino-2-fluorophenyl)-5- fluoromethyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][l,3]oxazin-2-yl]carbamate 25-(14) and 5-difluoromethyl-pyrazine-2-carboxylic acid according to General Procedure A. 1H NMR (400 MHz, CDCl3) delta (ppm): 2.94 (d, /=7.8 Hz, IH), 3.79 (dd, /=8.6, 2.5 Hz, IH), 3.89 – 4.05 (m, 2H), 4.28 – 4.66 (m, 4H), 6.72 (t, J 54.3 Hz, IH), 7.05 (dd, /=11.6, 8.8 Hz, IH), 7.67 (dd, /=7.1, 2.8 Hz, IH), 7.91 – 8.03 (m, IH), 8.85 (s, IH), 9.45 (s, IH), 9.61 (br s, IH)

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, 5-(Difluoromethyl)pyrazine-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; EISAI R&D MANAGEMENT CO., LTD; ELLARD, John Mark; FARTHING, Christopher Neil; HALL, Adrian; WO2011/9898; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 1174321-06-2, name is 5-(Difluoromethyl)pyrazine-2-carboxylic acid, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. name: 5-(Difluoromethyl)pyrazine-2-carboxylic acid

Example 193 N-(3-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4,5-difluorophenyl)-5-(difluoromethyl)pyrazine-2-carboxamide The title compound was synthesized by procedures and steps analogous to those described in Method Z, Example 186 above, but using 5-(difluoromethyl)pyrazine-2-carboxylic acid (Aurigene Discovery Technologies). MS m/z=466.1 [M+H]+. Calculated for C18H14F7N5O2: 465.32 1H NMR (300 MHz, CHLOROFORM-d) delta=9.65 (br. s., 1H), 9.52 (s, 1H), 8.93 (s, 1H), 8.14-8.02 (m, 1H), 7.15 (br. s., 1H), 6.99-6.60 (m, 1H), 4.13-3.98 (m, 1H), 2.81 (d, J=13.6 Hz, 1H), 1.94 (t, J=13.1 Hz, 1H), 1.67 (s, 3H)

The synthetic route of 5-(Difluoromethyl)pyrazine-2-carboxylic acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MINATTI, Ana Elena; LOW, Jonathan D.; ALLEN, Jennifer R.; CHEN, Jian; CHEN, Ning; CHENG, Yuan; JUDD, Ted; LIU, Qingyian; LOPEZ, Patricia; QIAN, Wenyuan; RUMFELT, Shannon; RZASA, Robert M.; TAMAYO, Nuria A.; XUE, Qiufen; YANG, Bryant; ZHONG, Wenge; US2014/249104; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 1174321-06-2, name is 5-(Difluoromethyl)pyrazine-2-carboxylic acid, A new synthetic method of this compound is introduced below., HPLC of Formula: C6H4F2N2O2

Example 211 N-(3-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-5-chloro-4-fluorophenyl)-5-(difluoromethyl)pyrazine-2-carboxamide The title compound was synthesized by procedures and steps analogous to those described in Method A2, Example 206 above, but using 5-(difluoromethyl)pyrazine-2-carboxylic acid (Aurigene Discovery Technologies Ltd.) in step 10. MS m/z=482.1 [M+H]+. Calculated for C18H14ClF6N5O2: 481.779 1H NMR (400 MHz, CHLOROFORM-d) delta=9.61 (br. s., 1H), 9.51 (s, 1H), 8.91 (s, 1H), 8.18 (dd, J=2.5, 6.1 Hz, 1H), 7.44-7.35 (m, 1H), 7.02-6.60 (m, 1H), 4.35 (br. s., 2H), 4.11-3.96 (m, 1H), 2.80 (dd, J=2.2, 13.9 Hz, 1H), 1.92 (t, J=13.2 Hz, 1H), 1.65 (s, 3H)

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; MINATTI, Ana Elena; LOW, Jonathan D.; ALLEN, Jennifer R.; CHEN, Jian; CHEN, Ning; CHENG, Yuan; JUDD, Ted; LIU, Qingyian; LOPEZ, Patricia; QIAN, Wenyuan; RUMFELT, Shannon; RZASA, Robert M.; TAMAYO, Nuria A.; XUE, Qiufen; YANG, Bryant; ZHONG, Wenge; US2014/249104; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 1174321-06-2,Some common heterocyclic compound, 1174321-06-2, name is 5-(Difluoromethyl)pyrazine-2-carboxylic acid, molecular formula is C6H4F2N2O2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

A mixture of Example 130E (0.05 g, 0.146 mmol), 5-(difluoromethyl)pyrazine-2- carboxylic acid (0.029 g, 0.168 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.102 mL, 0.583 mmol) in N,N-dimethylformamide (1.5 mL) was treated with 2-(3H-[l ,2,3]triazolo[4,5- Z?]pyridin-3-yl)- l ,l ,3,3-tetramethylisouronium hexafluorophosphate(V) (0.083 g, 0.219 mmol), and the reaction was stirred at ambient temperature for 30 minutes. Volatiles were removed under high vacuum, and the residue was purified by HPLC (10-95% acetonitrile in 0.1% trifluoroacetic acid/water on Phenomenex CI 8 5 mupiiota (250 mm x 21.2 mm) column at a flowrate of 25 mL/minute) to give 43 mg of the title compound as a solid. JH NMR (400 MHz, DMSO- ) delta ppm 9.19 (d, J = 1.4 Hz, 1H), 8.94 (d, J = 1.2 Hz, 1H), 8.03 (s, 1H), 7.45 (t, J = 8.9 Hz, 1H), 7.28 (d, J = 6.0 Hz, 1H), 7.16 (m, 1H), 7.07 6.98 (m, 1H), 6.80 (ddd, J = 9.0, 2.9, 1.2 Hz, 1H), 5.13 (d, J = 4.4 Hz, 1H), 4.44 (s, 2H), 4.08 (ddd, J = 9.9, 5.4, 3.1 Hz, 1H), 2.39 (ddd, J = 12.6, 9.5, 2.5 Hz, 1H), 2.13 2.01 (m, 2H), 1.95 (q, J = 4.8, 2.6 Hz, 1H), 1.94 1.76 (m, 6H); MS (ESI+) m/z 499.1 (M+H)+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-(Difluoromethyl)pyrazine-2-carboxylic acid, its application will become more common.

Reference:
Patent; CALICO LIFE SCIENCES LLC; ABBVIE INC.; MARTIN, Kathleen, Ann; SIDRAUSKI, Carmela; FROST, Jennifer, M.; PLIUSHCHEV, Marina, A.; TONG, Yunsong; BLACK, Lawrence, A.; XU, Xiangdong; SHI, Lei; ZHANG, Qingwei, I.; CHUNG, Seungwon; SWEIS, Ramzi, Farah; DART, Michael, J.; RANDOLPH, John, T.; MURAUSKI, Kathleen; (674 pag.)WO2019/90076; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 1174321-06-2, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 1174321-06-2, name is 5-(Difluoromethyl)pyrazine-2-carboxylic acid belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

1) Synthesis of Compound F-21: Compound F-19 (18 mg, 0.04 mmol) was dissolved in dichloromethane (3 mL),1H-benzotriazol-1-yloxytripyrrolidinylhexafluorophosphate (PyBOP) (57 mg, 0.1 mmol), diisopropylethylamine (21.6 muL, 0.13 mmol) was added,5-Difluoromethylpyrazine-2-carboxylic acid (16 mg, 0.09 mmol), reacted overnight at room temperature;TLC showed complete reaction of the raw materials, adding dichloromethane (5mL), and then saturated organic saline to wash the organic phase, the organic phase was dried by spin-drying the column product 23mg;Suggest an edit

The synthetic route of 5-(Difluoromethyl)pyrazine-2-carboxylic acid has been constantly updated, and we look forward to future research findings.