Category: 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. category: Pyrazines

Step 12: (+/-)-N-(3-((4aS*,7aS*)-2-amino-3-methyl-4-oxo-3,4,4a,5,7,7a-hexahydrofuro r3,4-dlpyrimidin-7a-yl)-4-fluorophenyl)-5-(difluoromethyl)picolinamide.(+/-)-tert-Butyl ((4aS*,7aS*)-7a-(5-amino-2-fluorophenyl)-3-methyl-4-oxo-3,4,4a,5,7,7a- hexahydrofuro[3,4-d]pyrimidin-2-yl)carbamate (11 mg , 0.03 mmol) was dissolved in DCM (2 mL). 5-(difluoromethyl)pyrazine-2-carboxylic acid (8 mg , 0.04 mmol) was transferred into the reaction vessel. N-ethyl-N-(propan-2-yl)propan-2-amine (7.5 mg, 0.06 mmol) was transferred in to the reaction vessel. N-[3-(dimethylamino)propyl]- N’-ethylcarbodiimide (7 mg, 0.04 mmol) was transferred into the reaction vessel.After 15 mins the reaction mixture was washed with HCl (IM, 2 x 2 mL) then with saturated aqueous NaHCO3 (2 x 2 mL). The organic phase was then concentrated and the crude mixture was taken directly to the next reaction. LCMS (Method A) Rt 5.44 min; ESI-MS: m/z 535 [M+H]+.

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

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, 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.

To an ice-water cooled mixture of tert-butyl[(4’R)-6′-amino-2′,2′-dimethyldispiro[cyclopropane-1,3′-chromene-4′,4″-[1,3]oxazol]-2″-yl]carbamate (430 mg, 1.15 mmol), 5-(difluoromethyl)pyrazine-2-carboxylic acid (221 mg, 1.27mmol) and lH-benzotriazol-1-ol (170 mg, 1.26 mmol) in chloroform (8.6 ml) was addedN-[3-(dimethylamino)propyl]-N’-ethylcarbodiimide hydrochloride (244 mg, 1.28 mmol). Themixture was stirred at room temperature overnight and directly purified by silica gel columnchromatography (precolumn: basic silica gel, main column: neutral silica gel, hexane/ethylacetate= 2:1- 1:1- 0:100) to afford tert-butyl[ ( 4’R)-6′-( { [5-( difluoromethyl)pyrazin-2-yl]carbonyl }amino )-2′ ,2′-dimethyldispiro[ cyclopropane-1,3′-chromene-4′,4″-[1,3]oxazol]-2″-yl]carbamate (373 mg).

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

Reference:
Patent; ASTELLAS PHARMA INC.; COMENTIS, INC.; MUNAKATA, Ryosuke; INOUE, Makoto; TOMINAGA, Hiroaki; YAMASAKI, Shingo; SHIINA, Yasuhiro; SAMIZU, Kiyohiro; HAMAGUCHI, Hisao; HONG, Lin; WO2013/181202; (2013); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application 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.

N,N-Dimethylformamide (2 mL), triethylamine (0.081 mL, 0.58 mmol) and 1- [bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (48 mg, 0.126 mmol, HATU) were added to a mixture of the product of Example 197B (40 mg, 0.097 mmol) and 5-(difluoromethyl)pyrazine-2-carboxylic acid (Manchester, 16.9 mg, 0.097 mmol) in sequential order. The reaction mixture was then stirred at ambient temperature for 0.5 hour. The resulting solution was filtered through a glass microfiber frit and purified by preparative HPLC [Waters XBridge C185 mum OBD column, 30 ¡Á 100 mm, flow rate 40 mL/minute, 5-100% gradient of acetonitrile in buffer (0.025 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to give the title compound (39 mg, 0.086 mmol, 88% yield). 1H NMR (500 MHz, DMSO-d6) delta ppm 9.34 (s, 1H), 9.31- 9.22 (m, 1H), 8.99 (s, 1H), 8.53 (s, 1H), 7.50 (t, J = 8.9 Hz, 1H), 7.21 (t, J = 54.0 Hz, 1H), 7.08 (dd, J = 11.4, 2.8 Hz, 1H), 6.86 (ddd, J = 9.0, 3.0, 1.1 Hz, 1H), 4.49 (s, 2H), 2.18 – 2.12 (m, 2H), 1.99- 1.80 (m, 6H); MS (ESI+) m/z 455 (M+H)+.

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; CALICO LIFE SCIENCES; ABBVIE, INC.; SIDRAUSKI, Carmela; PLIUSCHEV, Marina; FROST, Jennifer, M.; BLACK, Lawrence, A.; XU, Xiangdong; SWEIS, Ramzi, Farah; SHI, Lei; ZHANG, Qinwei, I.; TONG, Yunsong; HUTCHINS, Charles, W.; CHUNG, Seungwon; DART, Michael, J.; (661 pag.)WO2017/193063; (2017); 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.

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-[1,2,3]triazolo[4,5- b]pyridin-3-yl)-1,1,3,3-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 C185 mum (250 mm ¡Á 21.2 mm) column at a flowrate of 25 mL/minute) to give 43 mg of the title compound as a solid. 1H NMR (400 MHz, DMSO-d6) 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), 7.076.98 (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), 2.132.01 (m, 2H), 1.95 (q, J = 4.8, 2.6 Hz, 1H), 1.941.76 (m, 6H); MS (ESI+) m/z 499.1 (M+H)+.

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

Reference:
Patent; CALICO LIFE SCIENCES; ABBVIE, INC.; SIDRAUSKI, Carmela; PLIUSCHEV, Marina; FROST, Jennifer, M.; BLACK, Lawrence, A.; XU, Xiangdong; SWEIS, Ramzi, Farah; SHI, Lei; ZHANG, Qinwei, I.; TONG, Yunsong; HUTCHINS, Charles, W.; CHUNG, Seungwon; DART, Michael, J.; (661 pag.)WO2017/193063; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application 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.

Example 24 N-(3-((2R,5R)-6-amino-3,3,5-trifluoro-2,5-dimethyl-2,3,4,5-tetrahydropyridin-2-yl)-4-fluorophenyl)-5-(difluoromethyl)pyrazine-2-carboxamide Prepared from (3R,6R)-6-(5-amino-2-fluorophenyl)-3,5,5-trifluoro-3,6-dimethylpiperidine-2-thione and 5-(difluoromethyl)pyrazine-2-carboxylic acid LC-MS (m/z) 446 (MH+) tR=0.52 minutes (Method A) 1H NMR (600 MHz, DMSO-d6) delta 11.03 (s, 1H), 9.37 (t, J=2.4 Hz, 1H), 9.09 (s, 1H), 7.89-7.80 (m, 2H), 7.26 (t, J=53.9 Hz, 1H), 7.18 (dd, J=11.9, 8.7 Hz, 1H), 6.34 (s, 2H), 2.62-2.51 (m, 1H), 2.29-2.14 (m, 1H), 1.71 (d, J=23.2 Hz, 3H), 1.68 (s, 3H)

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

Reference:
Patent; H. LUNDBECK A/S; Juhl, Karsten; Marigo, Mauro; Tagmose, Lena; Jensen, Thomas; US2015/232449; (2015); A1;,
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. SDS of cas: 1174321-06-2

3Q-(Il) synthesis of ((lS,4aS,5R,7aS)-7a-{5-r(5-Difluoromethyl-pyrazine-2-carbonyl)- aminol-2-fluoro-phenyl|-5-methyl-4-trifluoromethyl-4a,5JJa-tetrahydro-4H-furor3,4- diri,31oxazin-2-yl)-carbamic acid tert-butyl estertert-butyl ((4S,4aS,5R,7aS)-7a-(5-amino-2-fluorophenyl)-5-methyl-4-(trifluoromethyl)- 4a,5,7,7a-tetrahydro-4H-furo[3,4-d][l,3]oxazin-2-yl)carbamate (Preparation Example 30-(1O)) (110.25 mg, 0.25 mmol) dissolved in DCM. 5-(difluoromethyl)pyrazine-2- carboxylic acid (66.43 mg, 0.38 mmol) added. Followed by N-ethyl-N-(propan-2- yl)propan-2-amine (65.75 mg, 0.51 mmol) and N-[(dimethylamino)(3H- [l,2,3]triazolo[4,5-b]pyridin-3-yloxy)methylidene]-N-methylmethanaminiumhexafluorophosphate (0.14 g, 0.38 mmol). The reaction was stirred at RT. LCMS (Agilent Method A) Retention time 5.44min, ES+: 535 [MH]+. After 15 min, the reaction mixture was washed with HCl IM (2 x 5mL) then washed with sat. NaHCO3 (2 x 5mL). The organic phase was then concentrated and the crude mixture was purified by flash chromatography. 140 mg (100%) of the title compound (85%) and its isomer (15%) were isolated as a mixture. 1H NMR (400 MHz, CDCl3) ppm 1.45 (d, /=6.19 Hz, 3H) 1.55 (s, 9H) 2.95 (dd, /=8.84, 2.65 Hz, IH) 3.89 (dd, /=8.84, 2.53 Hz, IH) 4.30 (qd, /=6.91, 2.27 Hz, IH) 4.48 (quin, /=6.44 Hz, IH) 4.56 (dd, /=(dd, /=11.68, 9.03 Hz, IH) 6.82 (t, /=54.20 Hz, IH) 7.22 (dd, /=11.6, 7.87 Hz, IH) 7.55 (dd, /=6.88, 2.84 Hz, IH) 8.26 (ddd, /=8.87, 4.14, 2.78 Hz, IH) 8.97 (s, IH) 9.55 (s, IH) 9.70 (s, IH)

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; EISAI R&D MANAGEMENT CO., LTD; ELLARD, John Mark; FARTHING, Christopher Neil; HALL, Adrian; WO2011/9898; (2011); 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, Application In Synthesis of 5-(Difluoromethyl)pyrazine-2-carboxylic acid

Step 6: tert-Butyl ((4aS,5SJaS)-7a-(5-(5-(difluoromethyl)pyrazine-2-carboxamido)-2- fluorophenyl)-3-ethyl-4-oxo-5-(trifluoromethyl)-3,4,4a,5JJa-hexahvdrofuror3,4- dlpyrimidin-2-yl)carbamate N-Ethyl-N-(propan-2-yl)propan-2-amine (190 muL, 1.1 mmol) was added to a stirred mixture of tert-butyl ((4aS,5S,7aS)-7a-(5-amino-2-fluorophenyl)-3-ethyl-4-oxo-5- (trifluoromethyl)-3,4,4a,5,7,7a-hexahydrofuro[3,4-d]pyrimidin-2-yl)carbamate (100 mg, 0.21 mmol), 5-(difluoromethyl)pyrazine-2-carboxylic acid (57 mg, 0.33 mmol) and (lH-benzotriazol-l-yloxy)(tripyrrolidin-l-yl)phosphonium hexafluorophosphate (170 mg, 0.33 mmol) in dry DCM (1 mL) at RT under nitrogen. The reaction was stirred at this temperature for 16 h, and 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, 1Og, Biotage SNAP cartridge KP-SiI, 12mL per min, gradient 5% to 30% EtOAc in n-hexane) to give the title compound (118 mg, cream foam). 1H NMR (400 MHz, CDCl3-d) delta ppm 1.14 (t, J=7.07 Hz, 3H) 1.56 (s, 9H) 3.96 – 4.15 (m, 3H) 4.39 (d, J=9.60 Hz, IH) 4.50 (dd, J=9.73, 2.91 Hz, IH) 4.53 – 4.62 (m, IH) 6.81 (t, J=54.60 Hz, IH) 7.22 (dd, J=10.74, 8.97 Hz, IH) 7.76 (dd, J=6.69, 2.65 Hz, IH) 7.79 – 7.84 (m, IH) 8.93 (s, IH) 9.52 (s, IH) 9.65 (s, IH) 10.64 (s, IH).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-(Difluoromethyl)pyrazine-2-carboxylic acid, and friends who are interested can also refer to 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