Month: March 2021

Application of 3984-14-3, A common heterocyclic compound, 3984-14-3, name is N,N-Dimethylsulfamide, molecular formula is C2H8N2O2S, 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.

Intermediate 3 1H-Indole-6-carboxamide, 2-bromo-3-cyclohexyl-N-[(dimethylamino)sulfonyl]-. 1,1′-Carbonyldiimidazole (1.17 g, 7.2 mmol) was added to a stirred solution of 2-bromo-3-cyclohexyl-1H-indole-6-carboxylic acid (2.03 g, 6.3 mmol) in THF (6 mL) at 22 C. The evolution of CO2 was instantaneous and when it slowed the solution was heated at 50 C. for 1 hr and then cooled to 22 C. N,N-Dimethylsulfamide (0.94 g, 7.56 mmol) was added followed by the dropwise addition of a solution of DBU (1.34 g, 8.8 mmol) in THF (4 mL). Stirring was continued for 24 hr. The mixture was partitioned between ethyl acetate and dilute HCl. The ethyl acetate layer was washed with water followed by brine and dried over Na2SO4. The extract was concentrated to dryness to leave the title product as a pale yellow friable foam, (2.0 g, 74%, >90% purity, estimated from NMR). 1H NMR (300 MHz, DMSO-D6) delta ppm 1.28-1.49 (m, 3H) 1.59-2.04 (m, 7H) 2.74-2.82 (m, 1H) 2.88 (s, 6H) 7.57 (dd, J=8.42, 1.46 Hz, 1H) 7.74 (d, J=8.78 Hz, 1H) 7.91 (s, 1H) 11.71 (s, 1H) 12.08 (s, 1H).An alternative method for the preparation of 1H-indole-6-carboxamide, 2-bromo-3-cyclohexyl-N-[(dimethylamino)sulfonyl]- is described below.To a 1 L four necked round bottom flask equipped with a mechanical stirrer, a temperature controller, a N2 inlet, and a condenser, under N2, was added 2-bromo-3-cyclohexyl-1H-indole-6-carboxylic acid (102.0 g, 0.259 mol) and dry THF (300 mL). After stirring for 10 min, CDI (50.3 g, 0.31 mol) was added portion wise. The reaction mixture was then heated to 50 oC for 2 h. After cooling to 30 oC, N,N-dimethylaminosulfonamide (41.7 g, 0.336 mol) was added in one portion followed by addition of DBU (54.1 mL, 0.362 mol) drop wise over a period of 1 h. The reaction mixture was then stirred at rt for 20 h. The solvent was removed in vacuo and the residue was partitioned between EtOAc and 1 N HCl (1:1, 2 L). The organic layer was separated and the aqueous layer was extracted with EtOAc (500 mL). The combined organic layers were washed with brine (1.5 L) and dried over MgSO4. The solution was filtered and concentrated in vacuo to give the crude product (111.0 g). The crude product was suspended in EtOAc (400 mL) at 60 oC. To the suspension was added heptane (2 L) slowly. The resulting suspension was stirred and cooled to 0 oC. It was then filtered. The filter cake was rinsed with small amount of heptane and house vacuum air dried for 2 days. The product was collected as a white solid (92.0 g, 83%). 1H NMR (MeOD, 300 MHz) delta 7.89 (s, H), 7.77 (d, J=8.4 Hz, 1H), 7.55 (dd, J=8.4 and 1.8 Hz, 1H), 3.01 (s, 6H), 2.73-2.95 (m, 1H), 1.81-2.05 (m, 8H), 1.39-1.50 (m, 2H); m/z 429 (M+H)+.

The synthetic route of 3984-14-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Bristol-Myers Squibb Company; US2008/171015; (2008); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Related Products of 16313-66-9,Some common heterocyclic compound, 16313-66-9, name is 2-Amino-5-bromobenzamide, molecular formula is C7H7BrN2O, 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 2-amino-5-bromobenzamide (7.8 g, 0.036 mol), 4-methyl pentanoic acid (8.41 g, 0.O72mmol), and TBTU (17.46 g, 0.054 mol) in DMF (100 mL) was added DIPEA (25 mL, 0.154 mol) and the reaction mixture was stirred at room temperature for 14 h. The reaction mixture was diluted with water (100 mL)and extracted with ethyl acetate (2 x 100 mL). The combined organic layers were washed with aq. sodium bicarbonate solution (100 mL) and brine (100 mL). The organic layer was dried over sodium sulfate, and the volatiles were evaporated to dryness. The residue was purified by silica gel column chromatography using a gradient of 40% ethyl acetate in hexanes and the required fractions were collectedand volatiles were evaporated to give 5-bromo-2-(4-methylpentanamido)benzamide (7.0 g, 0.022 mol, 55% yield) as a brown solid. LCMS (ESI) m/e 313.0 (bromo pattern) [(M+H), calcd for C13H18BrN2O2, 313.05]; LC/MS retention time (LC/MS Method = Column – YMC PACK TMS (3X5Omm), 3.0 rim; Mphase A: 2%MeCN98%H20 – 10mM NH4OAc; Mphase B : 98%ACN – 2%H20 -10 mM NH4OAC;Flow: 1.2 mL/min)): ti = 2.12 mm.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Amino-5-bromobenzamide, its application will become more common.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; HARTZ, Richard A.; AHUJA, Vijay T.; MACOR, John E.; BRONSON, Joanne J.; DASGUPTA, Bireshwar; DZIERBA, Carolyn Diane; NARA, Susheel Jethanand; KARATHOLUVHU, Maheswaran Sivasamban; (226 pag.)WO2016/53794; (2016); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

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. 20348-09-8, name is 2H-Pyrido[3,2-b][1,4]oxazin-3(4H)-one, This compound has unique chemical properties. The synthetic route is as follows., Product Details of 20348-09-8

EXAMPLE 1096-((l-(2-(3-Oxo-2H-pyrido[3,2-b][l,4]oxazin-4(3H)-yl)ethyl)-2- oxabicyclo[2.2.2]octan-4-ylamino)methyl)-2H-pyrido[3,2-b][l,4]oxazin-3(4H)-oneHydrochlorideStep 1tert-Butyl 1 -(2-(3-Oxo-2H-pyrido[3,2-b] [ 1 ,4]oxazin-4(3H)-yl)ethyl)-2- oxabicyclo[2.2.2]octan-4-ylcarbamateTo a suspension of sodium hydride (38.0 mg, 55%) in N,N-dimethylacetamide (5 mL) was added 2H-pyrido[3,2-b][l,4]oxazin-3(4H)-one (151 mg) under cooling with ice, the mixture was stirred at room temperature for 30 minutes. The mixture was added AC (151 mg) under cooling with ice, the mixture was stirred at room temperature for 1.5 hours and further stirred at 60 C for 4 hours. The mixture was concentrated in vacuo. After dilution of the residue with ethyl acetate, the mixture was added saturated ammonium chloride solution under cooling with ice. The organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered, and then concentrated in vacuo. Flash chromatography (silica, chloroform : ethyl acetate = 2: 1) of the residue gave tert-butyl l-(2-(3-oxo-2H-pyrido[3,2-b][l,4]oxazin- 4(3H)-yl)ethyl)-2-oxabicyclo[2.2.2]octan-4-ylcarbamate (84.0 mg).1H NMR (CDC13): delta 1.42 (s, 9H), 1.69-2.10 (m, 10H), 3.90 (s, 2H), 4.16-4.29 (m, 3H), 4.62 (d, J= 3.7 Hz, 2H), 6.90 (dd, J= 8.0, 4.9 Hz, 1H), 7.19 (dd, J= 7.3, 1.2 Hz, 1H), 8.01 (dd, J= 4.8, 1.2, Hz, 1H).MS (ESI+) m/z: 404 (MH+).HRMS (ESI+) for C2iH3oN305 (MH+): calcd, 404.21855; found, 404.21800.

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 20348-09-8.

Reference:
Patent; KYORIN PHARMACEUTICAL CO., LTD.; MERCK SHARP & DOHME CORP.; FUKUDA, Yasumichi; KAELIN, David E. Jr.; SINGH, Sheo B.; WO2013/3383; (2013); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 188345-71-3, name is 2-Boc-2-Azabicyclo[2.2.1]hept-5-ene, 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 188345-71-3, Safety of 2-Boc-2-Azabicyclo[2.2.1]hept-5-ene

2.22 Preparation of Compound 4 A stream of O3 was bubbled through a solution of compound 3 (8.0 g, 41 mmol) in CH3CO2H (21 mL) and DCM (350 mL) at -50-60 C. until the solution turned blue. Excess O3 was removed with O2, and Me2S (7.7 mL) was added dropwise to the solution. The mixture was allowed to warm gradually to rt and stirred for 16 h under N2. The solution was concentrated and the residue was used for the next step directly.

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, 2-Boc-2-Azabicyclo[2.2.1]hept-5-ene, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Hartman, George D.; US2015/132258; (2015); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Related Products of 21440-97-1, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 21440-97-1 as follows.

Example 6 Preparation of 6-bromo-4,4-dimethyl-benzoxazine-2-one Lithium Salt Similarly, 6-bromo-4,4-dimethyl-benzoxazine-2-one (2.55 g) was reacted with lithium tert-butoxide (10 mL of 1M solution in THF). After evaporation a brownish solid was obtained (3.35 g; quant. yield) that was soluble in dimethyl pyrimidone (DMPU) without heating. 1H NMR (DMSO-d6) did not show a peak corresponding to a N-H group.

According to the analysis of related databases, 21440-97-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Wyeth; US2005/250766; (2005); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Electric Literature of 16982-21-1, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 16982-21-1 name is Ethyl 2-amino-2-thioxoacetate, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

Ethyl thiooxamate (1.0 Kg, 7.52 mol) was added portion-wise to a solution of 2- bromopyruvic acid (1.38 Kg, 8.27 mol) in THF (4 L) over 20 min while the reaction was cooled with water bath. The reaction mixture was stirred for 12 h at room temperature. The reaction mixture was filtered to remove solid. The filtrate was concentrated to dryness to afford crude compound 70-1 (1.8 kg). The crude 70-1 was triturated with EtOAc/hexane/H20 (1 :3 :2, 6 L), filtered, and the solid was further triturated with EtO Ac/hexane (1 :8, 3 L), filtered, and the solid was dissolved in DCM (6 L), dried over anhydrous Na2S04, concentrated to afford compound 70-1 (617 g, 41% yield based on ethyl thiooxamate) as light yellow solid. 1H NMR (400 MHz, CDCI3): d 8.79 (s, 1H), 4.38-4.46 (q, J= 7.2 Hz, 2H), 1.3-1.38 (t, J= 7.2 Hz, 3H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Ethyl 2-amino-2-thioxoacetate, and friends who are interested can also refer to it.

Reference:
Patent; ARIAGEN, INC.; COLABUONO, Peter; JOHNSON, Graham; MANNING, David Douglas; WOLF, Mark Allan; (312 pag.)WO2019/99977; (2019); A2;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

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. 121496-39-7, name is tert-Butyl benzyl(2-hydroxyethyl)carbamate, A new synthetic method of this compound is introduced below., SDS of cas: 121496-39-7

Under nitrogen atmosphere, to an ice-cooled solution of 4-iodophenol (15.40 g), triphenylphosphine (22.03 g), and tert-butyl benzyl (2-hydroxyethyl) carbamate (21.05 g) in tetrahydrofuran (123 ml) was added diethyl azodicarboxylate (14.58 g) in tetrahydrofuran (31 ml) for 25 minutes, and the mixture was stirred at room temperature for 2 hours. After being concentrated, the mixture was treated with HEXANE/ETHYL acetate (5/1, 180 ml). The precipitate formed was filtered off, the filtrate was concentrated, and the residue was purified by column chromatography (silica gel, hexane/ethyl acetate) to give tert-butyl benzyl [2- (4- iodophenoxy) ethyl] carbamate (7.17 G) as a colorless oil. NMR (CDC13, B) : 1.45 (9H, s), 3.58 (2H, br s), 4.07 (2H, br s), 4.55 (2H, s), 6.62 (2H, d, J=8Hz), 7.10- 7.40 (5H, m), 7.53 (2H, d, J=8HZ) (+) ESI-MS (m/z): 476 (M+Na) +

The synthetic route of 121496-39-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; FUJISAWA PHARMACEUTICAL CO., LTD; WO2004/45610; (2004); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

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. 919475-15-3, name is 2-(4-(Benzyloxy)phenyl)-N,N-dimethylacetamide, A new synthetic method of this compound is introduced below., SDS of cas: 919475-15-3

A solution of 2N lithium diisopropylamide (LDA) (48.25 mL, 96.5 mmol) was cooled to -78¡ã C. and diluted with 25 mL of tetrahydrofuran (THF). To this was added dropwise, a solution of 2-(4-Benzyloxy-phenyl)-N,N-dimethyl-acetamide (20 g, 74.3 mmol) in 250 mL of THF. The mixture was warmed to 0¡ã C., then cooled back to -78¡ã C. A solution of 1,4-cyclohexanedione mono-ethylene ketal (14.1 g) in 350 mL of THF was added. The solution was allowed to warm to -20¡ã C. Highthroughput liquid chromatography (HPLC) assay still showed starting material. Another 1 g of ketal was added and the solution was warmed to 0¡ã C. for 2 hour. The reaction was quenched with a mixture of 25 g NH4Cl in 200 mL of water. EtOAc was added and the layers separated. The organic layer was dried with MgSO4, filtered and concentrated. Column chromatography (50percent EtOAc/hexanes) gave 30.3 g, 96percent yield of a solid

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; Wyeth; US2007/15828; (2007); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Electric Literature of 67046-22-4, The chemical industry reduces the impact on the environment during synthesis 67046-22-4, name is 6,7-Dihydro-5H-pyrido[2,3-b]azepin-8(9H)-one, I believe this compound will play a more active role in future production and life.

At -78C, 4.5 mL of 2.0 M lithium diisopropylamide-tetrahydrofuran solution and 300 mg of paraformaldehyde were added to tetrahydrofuran (30 mL) solution of 367 mg of the compound of the above 1, and gradually heated up to room temperature. At room temperature, this was stirred overnight, and then water was added to the reaction liquid and extracted with ethyl acetate. The ethyl acetate layer was dried with anhydrous sodium sulfate, the solvent was evaporated off under reduced pressure, and the residue was separated and purified through partitioning thin-layer chromatography (chloroform/methanol = 10/1) to obtain 111 mg of the entitled compound.

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, 6,7-Dihydro-5H-pyrido[2,3-b]azepin-8(9H)-one, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BANYU PHARMACEUTICAL CO., LTD.; EP1726590; (2006); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Reference of 142733-64-0,Some common heterocyclic compound, 142733-64-0, name is tert-Butyl (cis-3-(hydroxymethyl)cyclobutyl)carbamate, molecular formula is C10H19NO3, 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 solution of II-29-1 (200 mg, 1.0 mmol) and Et3N (202 mg, 2.0 mmol) in CH2C12(10 mL) was added MsCl (172 mg, 1.5 mmol) at 0 C. The reaction mixture was stirred at room temperature overnight before water was added to the reaction. The solution mixture was extracted with CH2C123 times. The organic layer was washed with brine and dried over Na2S04. The solution was filtered and concentrated to give II-29-2 as a white solid (250 mg, yield: 90%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route tert-Butyl (cis-3-(hydroxymethyl)cyclobutyl)carbamate, its application will become more common.

Reference:
Patent; KURA ONCOLOGY, INC.; BURROWS, Francis; KESSLER, Linda V.; LI, Liansheng; REN, Pingda; WANG, Yi; WU, Tao; ZHANG, Jingchuan; (355 pag.)WO2018/175746; (2018); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics