81282-60-2 | Heterocyclic Building Blocks-Benzoxazole

Application of 1,2-Thiazinane 1,1-dioxide

The chemical industry reduces the impact on the environment during synthesis,81282-60-2,7-Aminobenzo[d]oxazol-2(3H)-one,I believe this compound will play a more active role in future production and life.

81282-60-2, 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. 7-Aminobenzo[d]oxazol-2(3H)-one, cas is 81282-60-2,the benzoxazole compound, it is a common compound, a new synthetic route is introduced below.

To a solution of [6-(trifluoromethyl)-3-pyridyl)]-methanamine (lg, 4.7 mmol) in THF (30 mL) was added CDI (2.1 mol eq) and the mixture was heated at 70C overnight. The reaction mixture was evaporated, water was added and the aqueous phase was extracted with EtOAc (3×20 mL). The recombined organic phases were anhydrified over Na2SO4 and evaporated at reduced pressure (quantitative yield). The oil obtained (0.34g, 1.2 mmol) was dissolved in DMF (15 mL) and the bicyclic amine lc (Scheme 3) was added (0.8 mol eq), then the mixture obtained was heated at 100C overnight. The solvent was removed at reduced pressure and the residue was purified by chromatography (1 : 1 EtOAc:petroleum ether) to obtain the product as a white solid (0.064g, 20% Yield). ‘HNMR (DMSO, 200 MHz) delta 4.46 (d, 2H, J=6), 6.66 (d, 1H, J=8), 6.96 (t, 1H), 7.04 (bt, 1H), 7.64 (d, 1H, J=8), 7.86 (m, 2H), 8.70 (s, 1H), 8.77 (s, 1H), 1 1.60 (bs, 1H). [M+1] 358.02 (Ci5HnF3N4O3 requires 357.27).

Reference：
Patent; PHARMESTE S.R.L.; NAPOLETANO, Mauro; TREVISANI, Marcello; PAVANI, Maria Giovanna; FRUTTAROLO, Francesca; WO2011/120604; (2011); A1;,
Benzoxazole – Wikipedia
Benzoxazole | C7H5NO – PubChem

The important role of 81282-60-2

81282-60-2, 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.,81282-60-2 ,7-Aminobenzo[d]oxazol-2(3H)-one, other downstream synthetic routes, hurry up and to see

As a common heterocyclic compound, it belongs to benzoxazole compound, name is 7-Aminobenzo[d]oxazol-2(3H)-one, and cas is 81282-60-2, its synthesis route is as follows.

Amine 2b (795 mg, 3.3 mmol) (Scheme 7) was dissolved in 20 ml of AcOEt and at 0C triphosgene (979 mg, 3.3 mmol) was added to the solution. The mixture was warmed at 80C for 4 hours then evaporated and the residue was dissolved in 5ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound lc (330 mg, 2.2 mmol) and the mixture was warmed at 80C for 8 hours. (TLC AcOEt 1 / petroleum ether 1). The solvent was evaporated and the crude was dissolved in AcOEt (30 ml) and washed with water (1 X 20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column gave 240 mg of a white solid. Yield = 26% ‘HNMR (DMSO, 200 MHz) delta 1.91 (4H, m), 3.22 (4H, m), 4.38 (2H, d, J = 5.4 Hz), 6.66 (1H, dd, J = 7.6 Hz, J’ = 1.2 Hz), 7.00 (3H, m), 7.19 (1H, d, J = 8 Hz), 7.39 (1H, d), 7.72 (1H, dd, J = 8.6 Hz, J’ = 1), 8.72 (1H, bs), 1 1.63 (1H, bs); [M+1] 421.3 (C2oH19F3N4O3 requires 420.4).

Downstream synthetic route of 7-Aminobenzo[d]oxazol-2(3H)-one

As a common heterocyclic compound, it belongs to benzoxazole compound, name is 7-Aminobenzo[d]oxazol-2(3H)-one, and cas is 81282-60-2, its synthesis route is as follows.

To a solution of 2-aminomethyl-5-trifluoromethylfurane (lg, 6.1 mmol) in THF (30 mL) was added CDI (2.1 mol eq) and the mixture was heated at 70C overnight. The reaction mixture was evaporated, water was added and the aqueous phase was extracted with EtOAc (3×20 mL). The recombined organic phases were anhydrified over Na2SO4 and evaporated at reduced pressure(1.6g, 5.9 mmol). The oil obtained (0.3 lg, 1.19 mmol) was dissolved in DMF (20 mL) and the bicyclic amine lc (Scheme 3) was added (0.8 mol eq, 0.15g), then the mixture obtained was heated at 100C overnight. The solvent was removed at reduced pressure and the residue was purified by chromatography (100% EtOAc) to obtain the product as white solid (0.05g, 13% Yield). ‘HNMR (DMSO, 200 MHz) delta 4.37 (d, 2H, J=6), 6.48 (d, 1H, J=2), 6.70 (dd, 1H), 7.01 (m, 2H), 7.16 (m, 1H), 7.70 (dd, 1H, J=2), 8.69 (s, 1H), 1 1.62 (bs, 1H). [M+1] 341.61 (C14H10F3N3O4 requires 341.24).

Analyzing the synthesis route of 81282-60-2

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 7-Aminobenzo[d]oxazol-2(3H)-one, 81282-60-2

Example 1g. Preparation of bifeprunox MESYLATE (crude) A solution of 128.9 g of 3-[[BIS (2-HYDROXYETHYL) amino] METHYL]-1, 1′-biphenyl in approximately 750 ml of methylethylketone prepared according to Example 1f was stirred under mild nitrogen purge. In a separate vessel 202 g of METHANESULFONIC anhydride was dissolved in in 600 ml of methylethylketone at 10-20C. To the solution OF 3-[[BIS (2-HYDROXYETHYL) amino] METHYL]-1, 1′-biphenyl in methylethylketone 212.8 g of triethylamine was added and 60 ml of methylethylketone. The solution of methanesulfonic anhydride was added in about 45-60 minutes to the 3- [ [BIS (2- hydroxyethyl) AMINO] METHYL]-1, 1 -BIPHENYL/TRIETHYLAMINE solution, while maintaining the temperature below 10C. 60 ml of methylethylketone was added and the mixture was stirred for another 15 minutes, followed by drop wise addition of 109.7 g of METHANESULFONIC acid and addition of 60 mi of methylethylketone in order to rinse the addition vessel. 71.3 g of 7-amino-2 (3H)-BENZOXAZOLONE, prepared according to Example 1E was suspended in 100 mi of methylethylketone and added to the reaction mixture followed by 60 ml of methylethylketone. The reaction mixture was heated to reflux and refluxed during 20-24 hours. After 20-24 hours of reflux 48 ml of water was added and the mixture was refluxed again for 1 hour. 420 ml of methylethylketone was added and 490 ml of methylethylketone/water was distilled of. This last step was rep eated three times. 46. 1 G of METHANESULPHONIC acid was added, the mixture was refluxed for an additional hour and cooled down to room temperature in 1 hour. The mixture was further cooled down to 0-5C and stirred at this temperature for another hour. The solid was filtered off and, washed twice with 75 ml of cold METHYLETHYLKETONE, and dried at 50C and 100 mbar under a gentle nitrogen stream till dry. Yield about 76%.

Reference：
Patent; SOLVAY PHARMACEUTICALS B.V.; WO2005/16898; (2005); A2;,
Benzoxazole – Wikipedia
Benzoxazole | C7H5NO – PubChem

The important role of 81282-60-2

A solution of Ms20 (32 1 g, 184.8 mmol) in MeCN (200 mL) was cooled to < -5 C (ice/H20 salt) and sequentially were added a solution of N-benzyl-bis(2- hydroxyethyl)amine (16.4 g, 84.1 mmol) in MeCN (50 mL), Et3N (36 mL, 255 mmol, 3.8 eq.), and MsOH (13.1 mL, 202 mmol, 3 eq.) while maintaining the temperature below 10C. 7-Aminobenzo[d]oxazol-2(3H)-one (10.0 g, 67.2 mmol) was added as a solid and the mixture was heated to reflux. Et3N (28.5 mL, 202 mmol) was added drop- wise over a period of 1.5 hour. Reflux was maintained for 18 additional hours. The resulting clear solution was allowed to cool to RT and concentrated in vacuo at 70C. The residue was separated between NaHCC (0.8 L) and EtOAc (0.4 L). The aqueous layer was extracted with EtOAc (3 x 0.2 L). The combined organic layers were washed with brine, dried (NaiSC^) and concentrated to afford 7-(4-benzylpiperazin-l- yl)benzo[d]oxazol-2(3H)-one as a white solid (20.2 g, 65.3 mmol, 97%). The chemical industry reduces the impact on the environment during synthesis,81282-60-2,7-Aminobenzo[d]oxazol-2(3H)-one,I believe this compound will play a more active role in future production and life. Reference：
Patent; AAPA B.V.; HEERES, Andre; WILLIGERS – HOGG, Sandra; BORST, Marcus Leonardus Gerardus; DROeGE, Melloney Joyce; WO2015/69110; (2015); A1;,
Benzoxazole – Wikipedia
Benzoxazole | C7H5NO – PubChem

The important role of 81282-60-2

Example 36: 1-(4-(trifluoromethyl)-2-(piperidin-1-yl)benzyl)-3-(2,3-dihydro-2-oxobenzo[d]oxazol-7-yl)urea (scheme 1) Preparation of 1-(4-(trifluoromethyl)-2-(piperidin-1-yl)benzyl)-3-(2,3-dihydro-2-oxobenzo[d]oxazol-7-yl)urea Amine 2c (1 g, 3.8 mmol) was dissolved in 20 ml of AcOEt and at 0C triphosgene (1.13 g, 3.8 mmol) was added to the solution. The mixture was warmed at 80C for 4 hours then evaporated and the residue was dissolved in 5 ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound 1c (390 mg, 2.6 mmol) and the mixture was warmed at 80C for 8 hours. (TLC AcOEt1 / petroleum ether 1). The solvent was evaporated and the crude was dissolved in AcOEt (30 ml) and washed with water (1 X 20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column gave 160 mg of a white solid. Yield = 14% 1HNMR (DMSO, 200 MHz) delta 1.56 (2H, bs), 1.69 (4H, bs), 2.85 (4H, m), 4.42 (2H, d, J = 5.6 Hz), 6.66 (1H, dd, J = 8 Hz, J’ = 0.8 Hz), 7.01 (2H, m), 7.32 (1H, s), 7.44 (2H, dd, J = 7.6 Hz), 7.72 (1H, dd, J = 8.6 Hz, J’ = 1 Hz), 8.73 (1H, bs), 11.68 (1H, bs); [M+1] 435.2 (C21H21F3N4O3 requires 434.4).

Reference：
Patent; Pharmeste S.r.l.; EP2377850; (2011); A1;,
Benzoxazole – Wikipedia
Benzoxazole | C7H5NO – PubChem

Application of trans-Cyclohexane-1,2-diamine

To a mixture of 14.9 g N-methyldiethanolamine (3), 44.5 g triethylamine and 120 ml methyl ethyl ketone (MEK) a mixture of 51.6 g methanesulfonic anhydride and 100 ml MEK was dosed at 0 C. Subsequently 14.5 g methanesulfonic acid was dosed at 0 C. After which, 14.5 g 7-amino-2(3H)-benzoxazolone (2) was added and the mixture was heated to reflux followed by a reflux period of 48 hours during which the product crystallized. The product was filtered off after cooling to 0 C. and washed with MEK. The product was dried at 50 C. and 100 mbar to constant weight. The overall yield of this step was about 67% (crude on crude).

Reference：
Patent; Rheenen, Jeroen Van; Muijselaar, Wilhelmus G.H.M.; Teunissen, Hendrik; US2011/86862; (2011); A1;,
Benzoxazole – Wikipedia
Benzoxazole | C7H5NO – PubChem

Introduction of a new synthetic route about 81282-60-2

Example 35: 1-(4-(trifluoromethyl)-2-(pyrrolidin-1-yl)benzyl)-3-(2,3-dihydro-2-oxobenzo[d]oxazol-7-yl)urea (scheme 1) Preparation of 1-(4-(trifluoromethyl)-2-(pyrrolidin-1-yl)benzyl)-3-(2,3-dihydro-2-oxobenzo[d]oxazol-7-yl)urea Amine 2b (795 mg, 3.3 mmol) was dissolved in 20 ml of AcOEt and at 0C triphosgene (979 mg, 3.3 mmol) was added to the solution. The mixture was warmed at 80C for 4 hours then evaporated and the residue was dissolved in 5ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound 1c (330 mg, 2.2 mmol) and the mixture was warmed at 80C for 8 hours. (TLC AcOEt 1 / petroleum ether 1). The solvent was evaporated and the crude was dissolved in AcOEt (30 ml) and washed with water (1 X 20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column gave 240 mg of a white solid. Yield = 26% 1HNMR (DMSO, 200 MHz) delta 1.91 (4H, m), 3.22 (4H, m), 4.38 (2H, d, J = 5.4 Hz), 6.66 (1H, dd, J = 7.6 Hz, J’ = 1.2 Hz), 7.00 (3H, m), 7.19 (1H, d, J = 8 Hz), 7.39 (1H, d), 7.72 (1H, dd, J = 8.6 Hz, J’ = 1), 8.72 (1H, bs), 11.63 (1H, bs); [M+1] 421.3 (C20H19F3N4O3 requires 420.4).

Reference：
Patent; Pharmeste S.r.l.; EP2377850; (2011); A1;,
Benzoxazole – Wikipedia
Benzoxazole | C7H5NO – PubChem

Introduction of a new synthetic route about 81282-60-2

Amine 2c (1 g, 3.8 mmol) (Scheme 7) was dissolved in 20 ml of AcOEt and at 0C triphosgene (1.13 g, 3.8 mmol) was added to the solution. The mixture was warmed at 80C for 4 hours then evaporated and the residue was dissolved in 5 ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound lc (390 mg, 2.6 mmol) and the mixture was warmed at 80C for 8 hours. (TLC AcOEt 1 / petroleum ether 1). The solvent was evaporated and the crude was dissolved in AcOEt (30 ml) and washed with water (1 X 20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column gave 160 mg of a white solid. Yield = 14% 1HNMR (DMSO, 200 MHz) delta 1.56 (2H, bs), 1.69 (4H, bs), 2.85 (4H, m), 4.42 (2H, d, J = 5.6 Hz), 6.66 (1H, dd, J = 8 Hz, J’ = 0.8 Hz), 7.01 (2H, m), 7.32 (1H, s), 7.44 (2H, dd, J = 7.6 Hz), 7.72 (1H, dd, J = 8.6 Hz, J’ = 1 Hz), 8.73 (1H, bs), 1 1.68 (1H, bs); [M+1] 435.2 (C2iH21F3N4O3 requires 434.4).

Extracurricular laboratory: Synthetic route of 81282-60-2

Preparation of 1-(4-(trifluoromethyl)benzyl)-3-(2,3-dihydro-2-oxobenzo[d]oxazol-7-yl)urea Commercially available 4-trifluoromethylbenzylamine (1 ml, 7 mmol) was dissolved in 20 ml of AcOEt and at 0C triphosgene (2 g, 7 mmol) was added to the solution. The mixture was warmed at 80C for 4 hours then evaporated and the residue was dissolved in 5 ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound 1c (700 mg, 4.66 mmol) and the mixture was warmed at 80C for 8 hours. (TLC AcOEt 4 / petroleum ether 6). The solvent was evaporated and the crude was dissolved in AcOEt (30 ml) and washed with water (1 X 20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column gave 320 mg of a white solid. Yield = 19.5% 1HNMR (DMSO, 400 MHz) delta 4.41 (2H, d, J = 6 Hz), 6.67 (1H, dd, J = 7.6 Hz, J’ = 1.2 Hz), 7.00 (1H, t, J = 8 Hz), 7.09 (1H, t), 7.51 (2H, d, J = 8 Hz), 7.70 (3H, m), 8.73 (1H, s), 10.60 (1H, bs); [M+1] 352.1 (C16H12F3N3O3 requires 351.3).

Reference：
Patent; Pharmeste S.r.l.; EP2377850; (2011); A1;,
Benzoxazole – Wikipedia
Benzoxazole | C7H5NO – PubChem