Tag: M.W=200-300

Adding a certain compound to certain chemical reactions, such as: 127828-22-2, name is tert-Butyl (2-(2-aminoethoxy)ethyl)carbamate, 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 127828-22-2, category: amides-buliding-blocks

A solution of 6-chloro-4-hydroxy-5-methyl-3-nitropyridin-2(iH)-one (10.9 g, 53.4 mmol) in dichloromethane (380 mL) was cooled to 0 C. Triethylamine (22.3 mL, 160 mmol) was added, and the solution was stirred for ten minutes. Trifluoromethanesulfonic anhydride (18.0 mL, 107 mmol) was then added dropwise over a period of five minutes, and the solution was stirred for 1.5 hours at 0 C. A solution of tert-butyl 2-(2-aminoethoxy)ethylcarbamate (12.0 g, 58.8 mmol), prepared as described in Parts A through D of Example 102, in a small amount of dichloromethane was then added over a period of five minutes, and the reaction was allowed to warm to room temperature slowly and stirred overnight. The solution was then washed with water (2×150 mL) and brine (150 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluting sequentially with 80:20 hexanes:ethyl acetate and 50:50 hexanes:ethyl acetate) to provide a yellow oil, which was dissolved in diethyl ether and concentrated under reduced pressure to provide 16.5 g of trifluoromethanesulfonic acid 4-[(2-{2-[(tert-butoxycarbonyl)amino]ethoxy}ethyl)amino]-6-chloro-5-methyl-3-nitropyridin-2-yl ester as a solid.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, tert-Butyl (2-(2-aminoethoxy)ethyl)carbamate, and friends who are interested can also refer to it.

Reference:
Patent; Dellaria, Joseph F.; Lindstrom, Kyle J.; Dressel, Luke T.; Duffy, Daniel E.; Heppner, Philip D.; Jacobsen, John R.; Moseman, Joan T.; Moser, William H.; Radmer, Matthew R.; Stoermer, Doris; Zimmermann, Bernhard M.; US2004/10007; (2004); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Electric Literature of 42137-88-2,Some common heterocyclic compound, 42137-88-2, name is N,N-Bis(2-chloroethyl)-4-methylbenzenesulfonamide, molecular formula is C11H15Cl2NO2S, 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 (R)-1-(benzo[d][1,3]dioxol-5-yl)ethan-1-amine (2 g, 12.1 mmol) in DIPEA (4.22 mL, 24.2 mmol), N,N-bis(2-chloroethyl)-p-toluene sulfonamide (3.9 g, 13.3 mmol) was added at rt and the resulting mixture was heated to 105 C for 18 h. Completion of the reaction was confirmed by TLC. Reaction mixture was diluted with water (30 mL) and extracted with EtOAc (2 x 50 mL). The combined organic layer was dried over Na2SO4 and evaporated under vacuum. To the resulting crude solid hexane (50 mL) was added, and the resulting mixture was stirred for 10 min at rt. It was filtered and the solid was washed with Et2O (2 x 50 mL) and dried under vacuum to give the title compound. Yield: 63.8% (3 g, off white solid). 1H NMR (400 MHz, DMSO-d6): delta 7.59 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 6.81-6.77 (m, 2H), 6.69-6.6 (m, 1H), 5.97-5.95 (m, 2H), 3.35-3.31 (m, 1H), 2.81-2.80 (m, 4H), 2.42 (s, 3H), 2.36-2.32 (m, 4H), 1.18 (d, J= 6.8 Hz, 3H). LCMS: (Method A) 389.0 (M+H), Rt. 3.39 min, 98.9% (Max). HPLC: (Method A) Rt. 3.30 min, 99.53% (Max), Chiral HPLC: (Method A) Rt. 15.54 min, 97.58%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route N,N-Bis(2-chloroethyl)-4-methylbenzenesulfonamide, its application will become more common.

Reference:
Patent; ASCENEURON SA; QUATTROPANI, Anna; KULKARNI, Santosh S.; GIRI, Awadut Gajendra; (243 pag.)WO2016/30443; (2016); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Application of 143557-91-9, A common heterocyclic compound, 143557-91-9, name is tert-Butyl 3-endo-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate, molecular formula is C12H21NO3, 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 solution of tert-butyl (3-endo)-3-hyd roxy-8-azabicyclo[3.2.1 ]octane-8-carboxylate (3g, 13.20 mmol, combi-blocks) in THF (30 mL) was added portion wise potassium tertbutoxide (1.6 g, 14.5 mmol). The reaction was then refluxed for lh. The reaction was removed from the oil bath and 1-bromo-2,4-difluoro-benzene (1.6 mL, 14.52 mmol, Matrix) was added. The reaction was again refluxed for 1 .5h and cooled to RT. Ethyl acetate was added. The layers were separated and the organic layer was washed withwater, brine, dried over sodium sulphate, filtered and concentrated in vacuo. The crude was purified by flash chromatography using 5% ethyl acetate in cyclohexane to give a colourless oil that crystallised upon standing (4.1 g, 79%). 1H NMR (400 MHz, DMSOd 6): 67.63-7.59 (m, 1H), 6.98 (dd, J1= 11.40, J2= 2.76 Hz, 1H), 6.76-6.71 (m, 1H), 4.81 (t, J= 4.40 Hz, 1H), 4.06 (s, 2H), 2.15-2.05 (m, 4H), 1.87-1.84 (m, 4H), 1.41 (s, 9H).LCMS: (Method A) 344.0 (M-?Bu-f-H), Rt. 6.2 mm, 84.9% (Max).

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; ASCENEURON SA; QUATTROPANI, Anna; KULKARNI, Santosh S.; MURUGESAN, Kathiravan; BANERJEE, Joydeep; WO2014/198808; (2014); 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. 16313-66-9, name is 2-Amino-5-bromobenzamide, This compound has unique chemical properties. The synthetic route is as follows., Formula: C7H7BrN2O

12468] To a solution of compound 69-2 (22.0 g, crude product) in dry THF (250 mE), compound 69-5 (7.6 g, 35.5 mmol) and 1M NaOH (aq. 85 mE, 85 mmol) were added in turn. At the end of addition, the mixture was stirred at rt for 1 hr. After the reaction was completed, the mixture was extracted with EtOAc (100 mEx3). The combined organic layers were washed with 1M NaOH aqueous solution (15.0 mE) and brine, dried over Na2504 and concentrated in vacuo to give the title compound 6 9-6. The compound was characterized by the following spectroscopic data:12469] MS (ESI, pos.ion) mlz: 446.5 [M+H]12470] ?H NMR (400 MHz, CDC13) oe (ppm): 9.06 (br, 1H),7.75 (d, 1H), 7.35, 7.33 (d, d, 1H), 7.28-7.22 (m, 5H), 6.69,6.67 (d, d, 1H), 5.68 (brs, 2H), 5.14-5.13 (m, 2H), 4.29-4.25 (m, 1H), 3.66-3.60 (m, 1H), 3.45-3.37 (m, 1H), 2.39-2.32 (m, 1H), 2.09-2.00 (m, 1H), 1.96-1.77 (m, 2H).

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 16313-66-9.

Reference:
Patent; SUNSHINE LAKE PHARMA CO., LTD; Zhang, Yingjun; Zhang, Jaincun; Xie, Hongming; Ren, Qingyun; Tan, Yumei; Luo, Huichao; US2015/79028; (2015); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Synthetic Route of 67341-01-9, 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. 67341-01-9, name is tert-Butyl (2-hydroxy-1-phenylethyl)carbamate belongs to amides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

1-(2,6-difluoro-benzyl)-5-nitro-1H-pyrimidine-2,4-dione (82 mg, 0.29 mmol), ((R)-2-hydroxy-1-phenyl-ethyl)-carbamic acid tert-butyl ester (69 mg, 0.29 mmol), and triphenylphosphine (114 mg, 0.44 mmol) were dissolved in anhydrous tetrahydrofuran (2 mL). To this solution was added diethyl azodicarboxylate (200mu?, 0.44 mmol), followed by stirring at room temperature for 4 hrs. The solution was concentrated, after which the residue was purified using silica gel chromatography (eluent: hexane/ethyl acetate/dichloromethane, 3/1/1) and dried in a vacuum to afford 67 mg of the compound as a colorless oil (yield 67%). 1H NMR (300MHz, CDCl3) delta 1.30(9H, s), 3.40(1H, d), 4.50(1H, m), 5.08-5.27(4H, m), 7.02(2H, t), 7.26-7.47(6H, m), 8.78 (1H, s)

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, tert-Butyl (2-hydroxy-1-phenylethyl)carbamate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Sk Chemicals Co., Ltd.; EP2390250; (2011); A2;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

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 114790-39-5 as follows. Formula: C12H17NO4

A solution of benzyl N-(2,2-dimethoxyethyl)carbamate (50 g, 208.9 mmol) in toluene (180 mL) is treated with solid potassium hydroxide (51.6 g, 919.69 mmol) under nitrogen. After 10 minutes, benzyltriethylammonium chloride (0.8 g, 3.1 mmol) is added. After another 10 minutes a solution of allyl bromide (33 g, 272.8 mmol) in toluene (50 mL) is added dropwise over 10 minutes. The resultant mixture is stirred at 50 C for 48hours. The mixture is cooled to room temperature and quenched with water. The organic layer is separated, washed with brine, dried over magnesium sulfate, and concentrated to dryness to give the title compound (44 g, 75%). ES/MS (mlz): 280 (M+H).

According to the analysis of related databases, 114790-39-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ELI LILLY AND COMPANY; COATES, David Andrew; WOLFANGEL, Craig Daniel; (55 pag.)WO2016/122968; (2016); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Some common heterocyclic compound, 123986-64-1, name is tert-Butyl 4-(hydroxymethyl)benzylcarbamate, molecular formula is C13H19NO3, 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: tert-Butyl 4-(hydroxymethyl)benzylcarbamate

Stage 3 – Preparation of te/t-butyl (4-formylbenzyl)carbamate; Stage 2 product (5.87g, 24.73mmol) was stirred in DCM (20OmL) with MnO2 (16.71g, 192.2mmol) for 16h at RT. The reaction was then filtered through celite and the solvent removed in vacuo to give the product as a yellow oil (4.63g, 80%). m/z = 258 [M+Na]

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 123986-64-1, its application will become more common.

Reference:
Patent; CHROMA THERAPEUTICS LTD.; WO2008/40934; (2008); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Application of 25625-57-4,Some common heterocyclic compound, 25625-57-4, name is 2-Bromo-N-(3-(trifluoromethyl)phenyl)acetamide, molecular formula is C9H7BrF3NO, 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 10a Chiral isomer 12-{3-[4-(4-methyl-1 H-imidazol-1 -yl)phenyl]-2-oxo-7-oxa-1 ,4-diazaspiro[4.5]dec-3-en-1 -yl}-N-[3-(trifluoromethyl)phenyl]acetamide hydrochloride 3-[4-(4-Methyl-1 H-imidazol-1 -yl)phenyl]-7-oxa-1 ,4-diazaspiro[4.5]dec-3-en-2-one (D31 a), isomer 1 (94mg) in DMF (6ml) was cooled to ice bath temp and treated with sodium hydride 60% in oil (13mg) under an atmosphere of argon. The mixture was stirred for 20 minutes when 2-bromo-N-[3-(trifluoromethyl)phenyl]acetamide (85mg) in DMF (2.5ml) was added over 1.5 hours by syringe pump. The mixture was then allowed to warm to room temp overnight. The solvent was partially removed and the residue was purified by low pH MDAP. The fractions were loaded onto SCX and the free base was eluted with 2M methanolic ammonia. The solvent was removed and the residue was dissolved in DCM, treated with HCI-Et2O, solvent removed and a white solid was obtained from ether (78mg).1H NMR (DMSO) delta: 1.75 (2H, m), 2.05-2.35 (obs, m), 2.45 (3H, s), 3.4-3.6 (obs, m), 3.9 (2H, m), 4.98 (2H, m), 7.45 (1 H, m), 7.58 (1 H, m), 7.75 (1 H, m), 7.98 (2H, m), 8.12 (2H, m), 8.58 (2H, m), 9.63 (1 H, s), 10.74 (1 H, s). 19F NMR (DMSO) delta: 61.4 Mass Spectrum (LC/MS): Found 512 (MH+). Ret. time 1.63 min.Example 10b Chiral isomer 2 2-{3-[4-(4-methyl-1 H-imidazol-1 -yl)phenyl]-2-oxo-7-oxa-1 ,4-diazaspiro[4.5]dec-3-en- 1-yl}-N-[3-(trifluoromethyl)phenyl]acetamide-‘J 3-[4-(4-Methyl-1 H-imidazol-1 -yl)phenyl]-7-oxa-1 ,4-diazaspiro[4.5]dec-3-en-2-one (D31 b), isomer 2 (94mg) in DMF (6ml) was cooled to ice bath temp and treated with sodium hydride 60% in oil (12mg) under an atmosphere of argon. The mixture was stirred for 20 minutes when 2-bromo-N-[3-(trifluoromethyl)phenyl]acetamide (85mg) in DMF (2.5ml) was added over 1.5 hours by syringe pump. The mixture was then allowed to warm to room temp overnight. The mixture was poured into water and extracted with dichloromethane. The organic layer was washed with brine and then dried with hydromatrix and the solvent was removed to give the title compound (104mg). 1H NMR (CDCI3) delta: 1.7 (obs, m), 2.0 (2H, m), 2.15-2.4 (2H, m), 3.31 (3H, m), 3.71 (1 H, m), 3.85 (2H, m), 4.05 (1 H, m), 4.45 (2H, m), 7.10 (1 H, s), 7.3-7.5 (4H, m), 7.68 (1 H, m), 7.84 (1 H, m), 7.94 (1 H, m), 8.60 (2H, m), 9.09 (1 H, s). 19F NMR (DMSO) delta: 62.7 Mass Spectrum (LC/MS): Found 512 (MH+). Ret. time 1.62 min.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Bromo-N-(3-(trifluoromethyl)phenyl)acetamide, its application will become more common.

Reference:
Patent; GLAXO GROUP LIMITED; WO2009/34061; (2009); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Electric Literature of 7160-22-7,Some common heterocyclic compound, 7160-22-7, name is N-(3,4-Dichlorophenyl)pivalamide, molecular formula is C11H13Cl2NO, 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.

N-(3,4-dichlorophenyl)-2,2-dimethylpropanamide (121 g) was dissolved in 720 mL THF and the solution was cooled to -50 0C. Butyllithium (433 mL, 2.5N in hex) was added while keeping the internal temperature between -45 0C and -35 0C. (final temp.: -35 0C) and held at -25 0C for 40 min. An hplc check of the reaction mixture revealed that 5-10 % of the starting material remained. An additional 25 mL of butyllithium was added at -30 0C and the reaction was at -30 to – 25 0C for a further 30 min (HPLC: no significant change). The reaction mixture was cooled to -45 0C and SO2 was bubbled though the solution until saturation appeared to have been reached. Subsequently, the reaction mixture was at – 10 to 0 0C for 45 min. Argon (2 double -balloon volumes) was bubbled through the solution following which the reaction mixture was cooled to -5 0C. Sulfuryl chloride (58.8 mL) was added while keeping the temperature below 22 0C. The reaction mixture was kept at 10-15 0C for 1 h (HPLC: complete). EtOAc was added and the mixture was concentrated, washed with water, saturated aqueous sodium bicarbonate and brine, dried over MgStheta4 and the solvent was evaporated in vacuo. The crude material crystallized and was triturated with hot hexane. Yield: 87.2 g 1H-NMR (DMSOd6) delta 7.60(d, J= 8.4Hz, IH), 7.34(d, J= 8.4Hz, IH), 1.43(9H, s).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route N-(3,4-Dichlorophenyl)pivalamide, its application will become more common.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2007/124423; (2007); A2;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Application of 104060-23-3, 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. 104060-23-3 name is N-Boc-2-(4-Aminophenyl)ethanol, 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.

This compound (1.5 g, 8.6 mmol) was suspended in dry tetrahydrofuran (20 mL) at EPO 250C. The 4-(N-l-terf-butyloxycarbonyl)-aminophenethyl alcohol (3.4 g, 14.5 mmol) and triphenylphosphine (3.8 g, 14.5 mmol) were then added, and the mixture evaporated to dryness. Dry tetrahydrofuran (20 mL) was added and the suspension was cooled to 0C before dropwise addition of diethylazodicarboxylate (1.5 mL, 9.8 mmol). After 16 h reaction at room temperature, the solution was concentrated under reduced pressure. The crude residue was purified on a BIOTAGE 25M column (silica, hexane/AcOEt 95:5 to 75:25) to yield N-9 alkylated purine as a white solid (2.9 g, 87%). To a solution of alkylated 2-fluoro-6-chloropurine (3.0 g, 7.7 mmol) in n- butanol (15 mL) at 250C was added N- 1-tert-butyloxycarbonyl- 1,3 -phenyl enediamine (1.8 g, 8.8 mmol) and diisopropylethylamine (2.7 mL, 15.3 mmol). After 48 h reaction at 65C, the brown solution was concentrated under reduced pressure. The crude residue was purified on a BIOTAGE 4OM column (silica, hexane/ AcOEt 65:45 to 0:1) to yield the fluoropurine derivative as a brown solid (2.8 g, 63%). To a solution of this product (2.8 g, 4.9 mmol) in n-butanol (15 mL) at room temperature was added aminomethylcyclopropane (1.2 g, 17.1 mmol) and diisopropylethylamine (1.7 mL, 9.8 mmol). After 48 h reaction at 1100C, the brown solution was concentrated under reduced pressure. The crude residue was purified on a BIOTAGE 4OM column (silica, hexane/ AcOEt 60:40 to AcOEt/MeOH 98:2) to yield the protected trisubstituted purine as a white solid (2.3 g, 73%). To a solution of this compound (2.08 g, 3.38 mmol) in dichloromethane (10 mL) at room temperature was added 4N HCl in dioxane (10 mL). The reaction was stirred for 5 h at 25C and the solution was concentrated under reduced pressure. The solid was then dried for 16 h under vacuum to yield compound 3 as a brown solid. Yield of product: 1.4 g (quantitative); Rf = 0.1 (CH2Cl2/Me0H 98:2); 1H NMR (400 MHz, CD3OD): delta 8.24 (s, IH), 8.20-7.60 (m, 2H), 7.60-7.00 (m, 6H), 4.56 (t, 2H, J= 7.0 Hz), 3.40-3.20 (m, 4H), 1.25-1.15 (m, IH), 0.60-0.50 (m, 2H), 0.40-0.20 (m, 2H); LRMS (ESI): m/z 415 (MH+), 437 (M+ Na); HPLC (method 2): 1.6 min.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, N-Boc-2-(4-Aminophenyl)ethanol, and friends who are interested can also refer to it.

Reference:
Patent; PROMETIC BIOSCIENCES INC.; WO2006/136005; (2006); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics