147356-78-3 Archives - Amides-buliding-blocks

New downstream synthetic route of 147356-78-3

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, N-Methoxy-N-methylcyclopropanecarboxamide, other downstream synthetic routes, hurry up and to see.

Adding a certain compound to certain chemical reactions, such as: 147356-78-3, name is N-Methoxy-N-methylcyclopropanecarboxamide, belongs to amides-buliding-blocks 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 147356-78-3, category: amides-buliding-blocks

To a solution of (5S,7S)-2-bromo-5-(2,3-difluorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo[l,2- b][l,2,4]triazole (150 mg, 0.47 mmol), N-methoxy-N-methyl-cyclopropanecarboxamide (122 mg, 0.94 mmol) in tetrahydrofuran (3 mL) was added isopropylmagnesium chloride (2.0 M in tetrahydrofuran, 0.47 mL, 0.94mmol) dropwise at 0 C. After addition, the mixture was stirred at 0 C for 0.5 h and quenched by addition of saturated aqueous ammonium chloride (10 mL). The mixture was extracted with ethyl acetate (3 x 10 mL). The combined organic layers were washed with water (20 mL), brine (20 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by RP-HPLC (acetonitrile 40-70%o / 0.225%o formic acid in water) to afford arbitrarily assigned cyclopropyl-[(5S,7S)-5-(2,3-difluorophenyl)-7-fluoro-6,7-dihydro-5H- pyrrolo[l,2-b] [l,2,4]triazol-2-yl]methanone (49.1 mg, 34%) as a white solid. lR NMR (400 MHz, CDCl3) delta 7.22 – 7.16 (m, 1H), 7.14 – 7.08 (m, 1H), 6.75 – 6.72 (m, 1H), 6.13 – 6.10 (m, 0.5H), 5.99 – 5.96 (m, 0.5H), 5.88 – 5.84 (m, 1H), 3.74 – 3.67 (m, 1H), 3.09 – 3.04 (m, 1H), 2.99 – 2.92 (m, 1H), 1.36 – 1.31 (m, 2H), 1.14 – 1.09 (m, 2H). LC-MS RT = 0.666 min, m/z = 308.1 [M+H]+. LCMS (5 to 95%o acetonitrile in water + 0.03 %> trifluoacetic acid over 1.5 mins) retention time 0.666 min, ESI+ found [M+H] = 308.1.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; PATEL, Snahel; HAMILTON, Gregory; ZHAO, Guiling; CHEN, Huifen; DANIELS, Blake; STIVALA, Craig; (358 pag.)WO2019/12063; (2019); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

The important role of N-Methoxy-N-methylcyclopropanecarboxamide

Application of 147356-78-3, The chemical industry reduces the impact on the environment during synthesis 147356-78-3, name is N-Methoxy-N-methylcyclopropanecarboxamide, I believe this compound will play a more active role in future production and life.

Intermediate 402-Cyclopropyl-1H-pyrrolo[2,3-b]pyridine To a stirred mixture of lambda/-boc-2-aminopicoline (10.4g) in dry THF (70ml) in an ice/ salt bath was added, under an atmosphere of nitrogen, n-butyl lithium (2M solution in cyclohexane, 50ml), keeping the temperature below 00C. The reaction was stirred below 00C for 1 h before the addition of a solution of lambda/-methyl-lambda/-(methyloxy)cyclopropanecarboxamide (7.5g) (available from Pfaltz-Bauer) in dry THF (20ml). The reaction mixture was stirred at 00C for 2h then warmed to 100C and poured into 5M hydrochloric acid (130ml). The mixture was heated at 600C for 2h, cooled and the aqueous layer separated. The aqueous layer was basified by the addition of 10M sodium hydroxide, with ice/water cooling, until the pH was 10 – 12. The resulting mixture was extracted with DCM (2x100ml) and the combined organic extracts were washed with water (50ml), dried using a hydrophobic frit and evaporated to give the title compound (7.89g). LC/MS R1 0.78min m/z 159 [MH+]. Method B

Reference:
Patent; GLAXO GROUP LIMITED; WO2009/147188; (2009); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Continuously updated synthesis method about N-Methoxy-N-methylcyclopropanecarboxamide

The synthetic route of N-Methoxy-N-methylcyclopropanecarboxamide has been constantly updated, and we look forward to future research findings.

Reference of 147356-78-3, 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. 147356-78-3, name is N-Methoxy-N-methylcyclopropanecarboxamide belongs to amides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To a solution of (5S,7S)-2-bromo-7-fluoro-5-(2-fluorophenyl)-6,7-dihydro-5H-pyrrolo[l,2- b][l,2,4]triazole (500 mg, 1.67 mmol) and N-methoxy-N-methyl-cyclopropanecarboxamide (430 mg, 3.33 mmol) in tetrahydrofuran (10 mL) was added isopropylmagnesium chloride (2.0 M in tetrahydrofuran, 4.2 mL, 8.4 mmol) at 0 C under nitrogen atmosphere. The reaction mixture was stirred at 0C for 2 h and then quenched by addition of water (10 mL). The mixture was extracted with ether acetate (3 x 10 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to afford crude cyclopropyl-[(5S,7S)-7-fluoro-5-(2- fluorophenyl)-6,7-dihydro-5H-pyrrolo[l,2-b][l,2,4]triazol-2-yl]methanone (350 mg, 72%) as green oil.

The synthetic route of N-Methoxy-N-methylcyclopropanecarboxamide has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; CHEN, Huifen; HAMILTON, Gregory; PATEL, Snahel; ZHAO, Guiling; DANIELS, Blake; STIVALA, Craig; (208 pag.)WO2019/72942; (2019); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Introduction of a new synthetic route about C6H11NO2

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.

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. 147356-78-3, name is N-Methoxy-N-methylcyclopropanecarboxamide, A new synthetic method of this compound is introduced below., Formula: C6H11NO2

To the reaction flask, 2-(2-methoxyphenoxy)tetrahydropyran (8B) (200 g, 0.96 mol) and tetrahydrofuran (1000 ml) were added under nitrogenatmosphere, cooled to -20 C. with dry ice acetonebath, added nButyllithium(460 mL, 1.15 mol, 2.5M, Energy Chemical) dropwise slowly,stirred at -10 C. for 2 h. N-methyl-N-methoxyacetamide(186 g, 1.44 mol) was added and stirred at room temperature overnight. The reactionmixture was quenched with a saturated ammonium chloride solution (1000 mL), the organic phase was collected, washed with water (1000mL×2), brine (1000 mL×2), dried over anhydrous sodium sulfate and concentrated under vacuum to obtain cyclopropyl-(3-methoxy-2-tetrahydropyran-2-yloxy-phenyl)methanone (8C) as a red liquid (280 g, crude product), which was submitted to the next step without furtherpurification

Reference:
Patent; Sichuan Haisco Pharmaceutical Co., Ltd; Chin, Rinrin; Li, Fang chiong; Lee, Swi Swi; Luo, Huadong; Luo, Sin Pong; Wan, songrin; Ron, Ray; Liu, Guoliang; Wei, Yonggang; Liu, Chien Wi; Tang, Peongcho; (148 pag.)KR2016/5361; (2016); A;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Discovery of 147356-78-3

The synthetic route of 147356-78-3 has been constantly updated, and we look forward to future research findings.

Application of 147356-78-3, These common heterocyclic compound, 147356-78-3, name is N-Methoxy-N-methylcyclopropanecarboxamide, 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.

Isopropylmagnesium chloride (2.0 M in THF, 2.4 mL, 4.76 mmol) was added dropwise to a solution of a 2:1 mixture of (5S,7R)-2-bromo-5-(o-tolyl)-6,7-dihydro-5H-pyrrolo[l,2-b][l,2,4]triazol-7-ol and (5S,7R)-2-bromo-7-fluoro-5-(o-tolyl)-6,7-dihydro-5H-pyrrolo[l,2-b][l,2,4]triazole (0.470 g) and N- methoxy-N-methylcyclopropanecarboxamide (0.634 g, 4.76 mmol) in THF (15.9 mL) at 0C over 15 min. After lh, saturated aqueous ammonium chloride was added. The aqueous layer was extracted with isopropyl acetate (2 x 20 mL). The combined organic layers were dried over sodium sulfate, concentrated and the crude residue was purified by prep HPLC/SFC to afford arbitrarily assigned cyclopropyl((5S,7R)-7-fluoro-5-(o olyl)-6,7-dihydro-5H-pyrrolo[l,2-b][l ,2,4]triazol-2-yl)methanone (137 mg, 0.480 mmol) and cyclopropyl((5S,7R)-7-hydroxy-5-(o-tolyl)-6,7-dihydro-5H-pyrrolo[l,2- b][l,2,4]triazol-2-yl)methanone (33.8 mg, 0.119 mmol). cyclopropyl((5S,7R)-7-fluoro-5-(o-tolyl)-6,7-dihydro-5H-pyrrolo[l,2-b][l ,2,4]triazol-2- yl)methanone: NMR (400 MHz, DMSO-i) delta 7.33 – 7.14 (m, 3H), 6.89 (d, J= 7.5 Hz, 1H), 6.35 (ddd, J = 56.2, 6.8, 1.6 Hz, 1H), 6.19 (td, J = 6.9, 3.2 Hz, 1H), 3.59 – 3.27 (m, 1H), 3.11 – 2.91 (m, 2H), 2.38 (s, 3H), 1.14 – 1.01 (m, 4H). LCMS RT = 4.81 min, m/z = 286.1 [M + H]+. Prep SFC Information: Column: Torus Diol 5 muiotaeta, (150 x 30 mm), Mobile Phase: Carbon Dioxide (A) / 0.1 % Ammonium Hydroxide in Methanol (B), Elution Program Isocratic: 5% B Flow Rate: 150 mL/min, Column Temperature: 25 C, Wavelength: 220 nm cyclopropyl((5S,7R)-7-hydroxy-5-(o-tolyl)-6,7-dihydro-5H-pyrrolo[l,2-b][l,2,4]triazol-2- yl)methanone: NMR (400 MHz, DMSO-d6) delta 7.30 – 7.13 (m, 3H), 7.01 – 6.94 (m, 1H), 6.25 (bs, 1H), 5.75 (dd, J = 8.1, 5.8 Hz, 1H), 5.23 (dd, J = 7.9, 4.6 Hz, 1H), 3.63 – 3.52 (m, 1H), 3.03 – 2.92 (m, 1H), 2.38 (s, 3H), 2.31 – 2.14 (m, 1H), 1.09 – 0.96 (m, 4H). LCMS RT = 4.08 min, m/z = 284.1 [M + H]+. Prep HPLC Information: Column: Gemini-NX CI 8, 5muiotaeta (50 x 30 mm), Mobile Phase: 0.1 % Ammonium Hydroxide in Water (A) / Acetonitrile (B), Elution Program Gradient: 10% to 60%> B Flow Rate: 60 mL/min, Column Temperature: 25 C, Wavelength: 254 nm

The synthetic route of 147356-78-3 has been constantly updated, and we look forward to future research findings.

Introduction of a new synthetic route about 147356-78-3

To a mixture of (5S,7S)-2-bromo-5-(2,5-difluorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo[l,2- b][l,2,4]triazole (100 mg, 0.31 mmol), N-methoxy-N-methyl-cyclopropanecarboxamide (81 mg, 0.63 mmol) in tetrahydrofuran (3 mL) was added isopropylmagnesium chloride (2.0 M in tetrahydrofuran, 0.31 mL, 0.63 mmol) dropwise at 0 C. The mixture was stirred at 0 C for 0.5 h and quenched by addition of saturated aqueous ammonium chloride (10 mL). The mixture was extracted with ethyl acetate (3 x 10 mL). The combined organic layers were washed with water (20 mL), brine (20 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by preparative TLC to give cyclopropyl-[(5S,7S)-5-(2,5-difluorophenyl)-7-fluoro-6,7-dihydro-5H- pyrrolo[l ,2-b][l,2,4]triazol-2-yl]methanone (22.1 mg, 23%) as a white solid. H NMR (400 MHz, CD3OD) delta 7.28 – 7.17 (m, 2H), 6.93 – 6.88 (m, 1H), 6.22 – 6.06 (m, 1H), 5.90 – 5.86 (m, 1H), 3.88 – 3.74 (m, 1H), 3.09 – 3.02 (m, 1H), 2.93 – 2.82 (m, 1H), 1.21 – 1.18 (m, 2H), 1.15 – 1.11 (m, 2H). LCMS RT = 1.007 min, m/z = 308.1 [M+H]+. LCMS (10 to 80%o acetonitrile in water + 0.03%o trifluoacetic acid over 2 mins) retention time 1.007 min, ESI+ found [M+H] = 308.1.

Sources of common compounds: 147356-78-3

At the same time, in my other blogs, there are other synthetic methods of this type of compound, N-Methoxy-N-methylcyclopropanecarboxamide, and friends who are interested can also refer to it.

To a solution of N-methoxy-N-methyl-cyclopropanecarboxamide (1.2 g, 9.10 mmol) and [cis-2- bromo-7-deuterio-5-phenyl-5,6-dihydropyrrolo[l,2-b][l ,2,4]triazol-7-yl]oxy-tert-butyl-dimethyl- silane (1.8 g, 4.55 mmol) in tetrahydrofuran (40 mL) was added isopropylmagnesium chloride (2.0 M in tetrahydrofuran, 6.83 mL, 13.66 mmol) dropwise at 0 C. The mixture was stirred at 0 C for 1.5 h and quenched by addition of saturated aqueous ammonium chloride (50 mL). The mixture was extracted with ethyl acetate (3 x 50 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 100 – 200 mesh, 0 to 20% ethyl acetate in petroleum ether) to give [cis-7-[tert- butyl(dimethyl)silyl]oxy-7-deuterio-5-phenyl-5,6-dihydropyrrolo[l,2-b] [l,2,4] triazol-2-yl]- cyclopropyl-methanone (450 mg, 26%>) as a colorless oil. LCMS RT = 1.030 min, m/z = 384.2 [M + H]+. LCMS (5 to 95%> acetonitrile in water + 0.03 %> trifluoacetic acid over 1.5 mins) retention time 1.030 min, ESI+ found [M+H] = 384.2.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, N-Methoxy-N-methylcyclopropanecarboxamide, and friends who are interested can also refer to it.

The important role of 147356-78-3

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 147356-78-3.

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 147356-78-3, name is N-Methoxy-N-methylcyclopropanecarboxamide, This compound has unique chemical properties. The synthetic route is as follows., category: amides-buliding-blocks

Isopropylmagnesium chloride (2.0 M in THF, 2.0 mL, 3.97 mmol) was added to a solution of 2- bromo-7-fluoro-5-(l-methylpyrazol-4-yl)-6,7-dihydro-5H-pyrrolo[l,2-b][l,2,4]triazole (0.379 g, 1.32 mmol) and N-methoxy-N-methylcyclopropanecarboxamide (0.529 g, 3.97 mmol) in THF (13.2 mL) at 0C. After 5 min, the reaction was warmed to rt and stirred for an additional lh. Water was added and the reaction was diluted with isopropyl acetate. Brine was added and the aqueous layer was extracted with isopropyl acetate (4 x 50 mL). The combined organic layers were dried with sodium sulfate, concentrated and the crude residue was purified by prep SFC to afford arbitrarily assigned cyclopropyl((5S,7S)-7-fluoro-5-(l -methyl- lH-pyrazol-4-yl)-6,7-dihydro-5H-pyrrolo[ 1 ,2- b] [l ,2,4]triazol-2-yl)methanone (44.23 mg, 0.161 mmol, 12% yield). NMR (400 MHz, DMSO-d6) delta 7.80 (d, J = 0.8 Hz, 1H), 7.48 (d, J = 0.8 Hz, 1H), 6.21 (ddd, J= 56.4, 7.0, 2.4 Hz, 1H), 5.66 (ddd, J = 8.2, 6.0, 3.6 Hz, 1 H), 3.81 (s, 3H), 3.73 – 3.55 (m, 1H), 2.99 {XX, J = 7.5, 4.9 Hz, 1H), 2.80 (dddd, J = 26 A, 14.9, 3.7, 2.4 Hz, 1H), 1.14 – 0.95 (m, 4H). LCMS RT = 3.10 min, m/z = 276.1 [M + H]+. Prep SFC Information: Column: Whelko-01 5 muiotaeta, (150 x 21.2 mm), Mobile Phase: Carbon Dioxide (A) / 0.1 % Ammonium Hydroxide in Methanol (B), Elution Program Isocratic: 35% B Flow Rate: 70 mL/min, Column Temperature: 40 C, Wavelength: 220 nm.

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 147356-78-3.