Category: 1240390-36-6

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1240390-36-6,tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate,as a common compound, the synthetic route is as follows.

Step 1 6-Chloro-4-(6-methyl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide (150 mg, 0.57 mmol) and tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (185 mg, 0.85 mmol) were dissolved in 1,4-dioxane (2.8 mL) and N,N-diisopropylethylamine (0.25 mL, 1.4 mmol). The reaction mixture was stirred at 150 C. for 4 d. Further tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (50 mg, 0.23 mmol) and N,N-diisopropylethylamine (0.04 mL, 0.23 mmol) was added in four portions (every 36 h for 144 h). The mixture was cooled, and then water and ethyl acetate were added. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with sodium chloride solution and dried over sodium sulfate. After concentration, the residue was purified by chromatography (silica, 0 to 7% methanol in dichloromethane) to give {(3R,4R)-4-[6-carbamoyl-5-(6-methyl-pyridin-2-ylamino)-pyridazin-3-ylamino]-tetrahydro-pyran-3-yl}-carbamic acid tert-butyl ester (60 mg, 18%) as a clear amorphous residue. This was 83% pure and was used directly without further purification. MS (EI/CI) m/z: 444 [M+H]., 1240390-36-6

As the paragraph descriping shows that 1240390-36-6 is playing an increasingly important role.

Reference£º
Patent; Hoffman-La Roche Inc.; Hermann, Johannes Cornelius; Kennedy-Smith, Joshua; Lucas, Matthew C.; Padilla, Fernando; Soth, Michael; US2013/178478; (2013); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

1240390-36-6, tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate is a Tetrahydropyrans compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

1240390-36-6, Step 2 {(3R,4R)-4-[7-(1-methyl-1H-pyrazol-3-ylcarbamoyl)-thieno[3,2-d]pyrimidin-2-ylamino]-tetrahydro-pyran-3-yl}-carbamic acid tert-butyl ester To a solution of 2-chloro-thieno[3,2-d]pyrimidine-7-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide (0.103 g, 0.349 mmol) and tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (0.113 g, 0.524 mmol) in dioxane (4 mL) was added diisopropylethylamine (0.183 mL, 1.05 mmol). The reaction mixture was heated at 120 C. overnight. The reaction mixture was cooled and then diluted with dichloromethane, washed with aqueous sodium carbonate, then brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue obtained was then purified by chromatography (silica, 40 g, 0 to 15% MeOH in dichloromethane) to give {(3R,4R)-4-[7-(1-methyl-1H-pyrazol-3-ylcarbamoyl)-thieno[3,2-d]pyrimidin-2-ylamino]-tetrahydro-pyran-3-yl}-carbamic acid tert-butyl ester (0.127 g, 0.268 mmol, 76.8%) as a yellow solid. LCMS m/z [M+H]=474.

1240390-36-6 tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate 68077633, aTetrahydropyrans compound, is more and more widely used in various fields.

Reference£º
Patent; Hoffmann-La Roche Inc.; Chen, Shaoqing; Hermann, Johannes Cornelius; Le, Nam T.; Lucas, Matthew C.; Padilla, Fernando; US2013/178460; (2013); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

1240390-36-6, tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate is a Tetrahydropyrans compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Step 2 {(3R,4R)-4-[7-(5,6-Dimethyl-pyridin-2-ylcarbamoyl)-thieno[3,2-d]pyrimidin-2-ylamino]-tetrahydro-pyran-3-yl}-carbamic acid tert-butyl ester To a solution of 2-chloro-thieno[3,2-d]pyrimidine-7-carboxylic acid (5,6-dimethyl-pyridin-2-yl)-amide (0.149 g, 0.466 mmol) and tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (0.121 g, 0.559 mmol) in dioxane (4 mL) was added diisopropylethylamine (0.244 mL, 1.4 mmol). The reaction mixture was heated at 120 C. overnight. The reaction mixture was cooled and then diluted with dichloromethane, washed with aqueous sodium carbonate, then brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue obtained was then purified by chromatography (silica, 40 g, 0 to 15% EtOAc in hexanes) to give {(3R,4R)-4-[7-(5,6-dimethyl-pyridin-2-ylcarbamoyl)-thieno[3,2-d]pyrimidin-2-ylamino]-tetrahydro-pyran-3-yl}-carbamic acid tert-butyl ester (0.105 g, 0.210 mmol, 45%) as a yellow solid. LCMS m/z [M+H]=499.

1240390-36-6, 1240390-36-6 tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate 68077633, aTetrahydropyrans compound, is more and more widely used in various fields.

Reference£º
Patent; Hoffmann-La Roche Inc.; Chen, Shaoqing; Hermann, Johannes Cornelius; Le, Nam T.; Lucas, Matthew C.; Padilla, Fernando; US2013/178460; (2013); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1240390-36-6,tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate,as a common compound, the synthetic route is as follows.

Step 5 tert-Butyl (3R,4R)-4-(6-carbamoyl-5-(5-isopropyl-6-methoxypyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate To a solution of 6-chloro-4-(5-isopropyl-6-methoxypyridin-2-ylamino)pyridazine-3-carboxamide (250 mg, 777 mumol) in NMP (2.6 mL) was added tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (672 mg, 2.33 mmol) in four portions approximately every 12 h and heated to 140 C. in the periods between additions. After a total of 48 h, the mixture was cooled then diluted with ethyl acetate and brine. The phases were separated then the organic phase was washed with brine (2*), concentrated in vacuo and purified by chromatography (silica, 0 to 4% of a 99.5:0.5 methanol:NH4OH solution in dichloromethane) to give tert-butyl (3R,4R)-4-(6-carbamoyl-5-(5-isopropyl-6-methoxypyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (141 mg, 281 mumol, 36%) as light brown solid. MS (EI/CI) m/z: 502.3 [M+H]., 1240390-36-6

The synthetic route of 1240390-36-6 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; Hoffman-La Roche Inc.; Hermann, Johannes Cornelius; Kennedy-Smith, Joshua; Lucas, Matthew C.; Padilla, Fernando; Soth, Michael; US2013/178478; (2013); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

1240390-36-6, tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate is a Tetrahydropyrans compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Step 7 tert-Butyl (3R,4R)-4-(6-carbamoyl-5-(5-fluoro-6-isopropylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate To a solution of 6-chloro-4-(5-fluoro-6-isopropylpyridin-2-ylamino)pyridazine-3-carboxamide (250 mg, 807 mumol) in NMP (3.2 mL) was added tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (174 mg, 807 mumol) and the mixture heated to 140 C. Over the next 36 h three additional portions of tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (174 mg, 807 mumol) were added at 12 h intervals. At 48 h the mixture was cooled, diluted with EtOAc, and washed with water and brine (2*). The organic layer was concentrated onto silica and purified by chromatography (70% to 100% EtOAc in hexanes) to give tert-butyl (3R,4R)-4-(6-carbamoyl-5-(5-fluoro-6-isopropylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (100 mg, 25%). 1H NMR (400 MHz, CHLOROFORM-d6) delta ppm 11.49 (s, 1H), 8.22 (s, 1H), 8.06 (br. s, 1H), 7.29 (t, J=9.4 Hz, 1H), 6.70 (dd, J=8.9, 3.0 Hz, 1H), 6.07 (br. s, 1H), 5.50 (br. s, 1H), 5.35 (br. s, 1H), 4.26 (br. s, 1H), 4.03 (m, 2H), 3.92 (d, J=11.4 Hz, 1H), 3.68 (d, J=11.5 Hz, 1H), 3.61 (t, J=11.8 Hz, 1H), 3.41 (m, 1H), 2.24 (d, J=11.2 Hz, 1H), 1.81 (m, 1H), 1.49 (s, 9H), 1.35 (d, J=6.9 Hz, 6H)., 1240390-36-6

As the paragraph descriping shows that 1240390-36-6 is playing an increasingly important role.

Reference£º
Patent; Hoffman-La Roche Inc.; Hermann, Johannes Cornelius; Kennedy-Smith, Joshua; Lucas, Matthew C.; Padilla, Fernando; Soth, Michael; US2013/178478; (2013); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

1240390-36-6, tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate is a Tetrahydropyrans compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Step 3 6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-4-(5,6-dimethylpyridin-2-ylamino)pyridazine-3-carboxamide 6-Chloro-4-(5,6-dimethylpyridin-2-ylamino)pyridazine-3-carboxamide (120 mg, 432 mmol) and tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (187 mg, 864 mumol) in N-methyl-2-pyrrolidinone (6 mL) was heated at 150 C. for 1.5 d. After solvent evaporation, the residue was dissolved in dichloromethane (2 mL) and TFA (370 mg, 250 muL, 3.24 mmol). The mixture was stirred at room temperature for 3 h, then the solvent was evaporated and the residue was purified by chromatography (spherical silica, 20-45 mum, 11 g, Versaflash from Supelco, 97:2.75:0.15 to 87:12.35:0.65 dichloromethane:MeOH:NH4OH, 20 min) to afford a brown solid. The brown solid was dissolved in dichloromethane and 10 mL of cyclohexane was added. After standing, a solid precipitate formed. The supernatant was decanted and the solid residue was dried under vacuum to give 6-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-4-(5,6-dimethylpyridin-2-ylamino)pyridazine-3-carboxamide (18 mg, 12% over two steps) as a brown solid. 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 11.23 (br. s., 1H) 8.29 (s, 1H) 8.03 (br. s., 1H) 7.36 (d, J=8.08 Hz, 1H) 6.67 (d, J=8.08 Hz, 1H) 5.68-5.79 (m, 1H) 5.39 (br. s., 1H) 4.02 (d, J=7.33 Hz, 1H) 3.88 (d, J=11.12 Hz, 1H) 3.69 (d, J=11.62 Hz, 1H) 3.55 (t, J=11.49 Hz, 1H) 3.10 (br. s., 1H) 2.49 (s, 3H) 2.25 (s, 3H) 2.02 (d, J=12.38 Hz, 1H) 1.42-1.84 (m, 3H); LCMS (EI/CI) m/z: 358 [M+H]., 1240390-36-6

The synthetic route of 1240390-36-6 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; Hoffman-La Roche Inc.; Hermann, Johannes Cornelius; Kennedy-Smith, Joshua; Lucas, Matthew C.; Padilla, Fernando; Soth, Michael; US2013/178478; (2013); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

1240390-36-6, tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate is a Tetrahydropyrans compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Step 2 {(3R,4R)-4-[7-(Imidazole[1,2-b]pyridazin-3-ylcarbamoyl)-thieno[3,2-d]pyrimidin-2-ylamino]-tetrahydro-pyran-3-yl}-carbamic acid tert-butyl ester To a solution of 2-chloro-thieno[3,2-d]pyrimidine-7-carboxylic acid imidazol[1,2-b]pyridazin-3-ylamide (0.154 g, 0.466 mmol) and of tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (0.121 g, 0.559 mmol) in dioxane (4 mL) was added diisopropylethylamine (0.244 mL, 1.4 mmol). The reaction mixture was heated at 120 C. overnight. The reaction mixture was cooled and then diluted with dichloromethane, washed with aqueous sodium carbonate, then brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue obtained was then purified by chromatography (silica, 40 g, 0 to 15% MeOH in dichloromethane) to give {(3R,4R)-4-[7-(imidazole[1,2-b]pyridazin-3-ylcarbamoyl)-thieno[3,2-d]pyrimidin-2-ylamino]-tetrahydro-pyran-3-yl}-carbamic acid tert-butyl ester (0.163 g, 0.319 mmol, 68.5%) as a yellow solid. LCMS m/z [M+H]=511.

1240390-36-6, As the paragraph descriping shows that 1240390-36-6 is playing an increasingly important role.

Reference£º
Patent; Hoffmann-La Roche Inc.; Chen, Shaoqing; Hermann, Johannes Cornelius; Le, Nam T.; Lucas, Matthew C.; Padilla, Fernando; US2013/178460; (2013); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

1240390-36-6, tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate is a Tetrahydropyrans compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

Example 27 6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-4-(6-isopropyl-5-methylpyridin-2-ylamino)pyridazine-3-carboxamide A mixture of 6-chloro-4-(6-isopropyl-5-methylpyridin-2-ylamino) pyridazine-3-carboxamide (223 mg, 729 mumol, prepared as described in example 25), tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (315 mg, 1.46 mmol) and NMP (4 mL) was stirred at 140 C. for 18 h. The NMP was distilled off using a Kugelrohr apparatus under high vacuum to give a light brown solid. The crude material was dissolved in dichloromethane and MeOH and adsorbed on silica gel, then purified by chromatography (spherical silica 20-45 mum, 11 g, Versaflash from Supelco, eluting with 100% dichloromethane to 88:11.4:0.6 dichloromethane:methanol:NH4OH over 40 min) to give 109 mg of intermediate as a brown solid. This intermediate was dissolved in dichloromethane (2 mL) and TFA (740 mg, 500 muL, 6.49 mmol) was added. The mixture was stirred at room temperature for 16 h. The TFA and the dichloromethane were concentrated in vacuo and the residue obtained was purified by chromatography (spherical silica 20-45 mum, 11 g, Versaflash from Supelco, eluting with 100% dichloromethane to 88:11.4:0.6 dichloromethane:methanol:NH4OH over 40 min) to give a brown solid. The solid was suspended in 0.5 mL heptane and 10 drops of ethanol. The mixture was briefly sonicated and then heated, then cooled and the solvents decanted. The solid residue was dried overnight under high vacuum to give 6-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-4-(6-isopropyl-5-methylpyridin-2-ylamino)pyridazine-3-carboxamide (22 mg, 8%) as a brown solid. 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 11.18-11.31 (m, 1H), 8.26 (s, 1H), 7.95 (br. s., 1H), 7.26 (d, J=8.34 Hz, 1H), 6.55 (d, J=8.08 Hz, 1H), 5.73 (d, J=7.33 Hz, 1H), 5.29 (br. s., 1H), 3.99 (br. s., 1H), 3.90 (d, J=8.08 Hz, 1H), 3.78 (d, J=11.37 Hz, 1H), 3.66 (q, J=7.07 Hz, 1H), 3.57 (d, J=11.37 Hz, 1H), 3.44 (t, J=11.12 Hz, 1H), 3.20 (dt, J=13.33, 6.60 Hz, 1H), 2.97 (br. s., 1H), 2.21 (s, 3H), 1.89 (d, J=11.12 Hz, 1H), 1.61-1.77 (m, 1H), 1.25 (dd, J=6.57, 3.54 Hz, 6H), 1.18 (t, J=7.07 Hz, 1H); LC-MS 386 [M+H]+., 1240390-36-6

The synthetic route of 1240390-36-6 has been constantly updated, and we look forward to future research findings.

Reference£º
Patent; Hoffman-La Roche Inc.; Hermann, Johannes Cornelius; Kennedy-Smith, Joshua; Lucas, Matthew C.; Padilla, Fernando; Soth, Michael; US2013/178478; (2013); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1240390-36-6,tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate,as a common compound, the synthetic route is as follows.

Step 1 tert-Butyl (3R,4R)-4-(6-carbamoyl-5-(5-methoxy-6-propylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate To a solution of 6-chloro-4-(5-methoxy-6-propylpyridin-2-ylamino)pyridazine-3-carboxamide (200 mg, 622 mumol, prepared as described in example 31) in NMP (2.1 mL) was added tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (402 mg, 1.86 mmol) in 3 portions approximately every 12 h and heated to 140 C. in the periods between additions. After a total of 36 h, the mixture was cooled, diluted with ethyl acetate and brine, then the organic phase separated and washed with brine (3*). The organic phase was then concentrated in vacuo and the residue obtained was purified by chromatography (silica, 1 to 5% methanol in dichloromethane) to give tert-butyl (3R,4R)-4-(6-carbamoyl-5-(5-methoxy-6-propylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (77 mg, 154 mumol, 25%) as a light brown solid. MS (EI/CI) m/z: 502.2 [M+H].

1240390-36-6, 1240390-36-6 tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate 68077633, aTetrahydropyrans compound, is more and more widely used in various fields.

Reference£º
Patent; Hoffman-La Roche Inc.; Hermann, Johannes Cornelius; Kennedy-Smith, Joshua; Lucas, Matthew C.; Padilla, Fernando; Soth, Michael; US2013/178478; (2013); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1240390-36-6,tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate,as a common compound, the synthetic route is as follows.

1,1-dimethylethyl [(3R,4R)-4-({5-(aminocarbonyl)-4-[(4-methylphenyl)amino]-2- pyrimidinyl}amino)tetrahydro-2H-pyran-3-yl]carbamateA mixture of 1 ,1-dimethylethyl [(3R,4R)-4-aminotetrahydro-2H-pyran-3-yl]carbamate (38g), 2-chloro-4-[(4-methylphenyl)amino]-5-pyrimidinecarboxamide (46.2g) and triethylamine (49.0ml) in DMF (250ml) was heated and stirred at 900C. The mixture was added to water (11) and the solid precipitate collected by filtration. The precipitate was washed with water (2 x 200ml) and dried overnight at 4O0C in vacuo. The product was suspended in ethyl acetate (600ml) and heated to reflux for 30min, cooled in ice to 5C and the product collected by filtration. This was washed with ethyl acetate (2x 100ml) and dried at 400C in vacuo to give 1 ,1-dimethylethyl [(3R,4R)-4-({5-(aminocarbonyl)-4-[(4-methylphenyl)amino]-2- pyrimidinyl}amino)tetrahydro-2H-pyran-3-yl]carbamate (53.Og). LCMS (Method A): Rt 1.05min, MH+ 443.Variable temperature 1 H NMR (400MHz, D6-DMSO, 119C): deltaH 1 1.21 (1 H, bs),8.55(1 H, s), 7.53(2H, m), 7.14(4H, m), 6.57(1 H, d), 6.01 (1 H, d), 4.21 (1 H, m), 3.91-3.78(3H, m), 3.51-3.42(2H, m), 2.30(3H, s), 2.00-1.88(1 H, m), 1.74-1.62(1 H, m),1.37(9H, s)., 1240390-36-6

1240390-36-6 tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate 68077633, aTetrahydropyrans compound, is more and more widely used in various fields.

Reference£º
Patent; GLAXO GROUP LIMITED; ATKINSON, Francis, Louis; PATEL, Vipulkumar, Kantibhai; WO2010/97248; (2010); A1;,
Tetrahydropyran – Wikipedia
Tetrahydropyran – an overview | ScienceDirect Topics