Category: 1337532-51-0

Application of 1337532-51-0 ,Some common heterocyclic compound, 1337532-51-0, molecular formula is C7H7BrN4, 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.

A mixture of 5-bromo-7-methyl-7/-/-pyrrolo[2,3-c]pyrimidin-4-amine (0.31 g, 1.37 mmol), 1- [4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)phenyl]-3-[3-(trifluoromethyl)phenyl]-2- pyrrolidinone (0.59 g, 1.37 mmol), Pd2(dba)3 (63 mg, 0.07 mmol) and K3P04 (0.63 g, 2.74 mmol) in 10 mL of dioxane and 3.3 mL of water in a 20 mL microwave vial was bubbled with argon for 10 min, and then tri-(t-butyl)phosphonium tetrafluoroborate (40 mg, 0.14 mmol) was added. The mixture was capped and heated in a metal matrix block at 100 C. After 18 h, LCMS showed conversion complete. The mixture was filtered. The filtrate was concentrated in vacuo. The residue was taken up in water (30 mL) to give a suspension, which was filtered. The solid cake was washed with water and ether. The cake was dried under house vacuum, dissolved in 10% MeOH in DCM. The organic was dried over Na2S04, filtered, and concentrated in vacuo. The residue was dissolved in 10% MeOH in DCM and was absorbed onto a dryload silica gel cartridge. Purification was performed on a 115 g silica gel cartridge using gradient elution of 1 % A to 60% A in CHCI3 (A was a mixture of 3200/800/80 CHCI3/MeOH/NH4OH). The desired product eluted from 25-30% A. The combined fractions containing pure product were concentrated in vacuo. The residue was dissolved in 10% MeOH in CHCI3 and filtered. The filtrate was concentrated in vacuo and the residue was dissolved in 10% MeOH in DCM (12 mL), to which was added MTBE (15 mL). Solids slowly formed, resulting in a suspension. This mixture was concentrated in vacuo to reduce to half volume, followed by addition of another 15 mL of MTBE. The suspension was filtered. The cake was washed with MTBE (2 x 5 mL) and hexane (2 x 4 mL), dried under vacuum at 65 C for 20 h to afford 1-4-(4-amino-7-methyl- 7/-/-pyrrolo[2,3-c]pyrimidin-5-yl)phenyl)-3-(2,5-difluorophenyl)pyrrolidin-2-one (449 mg) as an off-white solid. LCMS (ES) m/z = 452 [M+H]+. H NMR (400 MHz, DMSOd6) delta ppm 2.22 – 2.35 (m, 1 H), 2.58 – 2.71 (m, 1 H), 3.75 (s, 3 H), 4.00 (dd, J=8.8, 5.3 Hz, 2 H), 4.17 (t, J=9.6 Hz, 1 H), 5.97 – 6.18 (br s, 1.2 H), 7.32 (s, 1 H), 7.49 (d, J=8.6 Hz, 2 H), 7.60 – 7.70 (m, 3 H), 7.73 (s, 1 H), 7.83 (d, J=8.8 Hz, 2 H), 8.16 (s, 1 H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,1337532-51-0, its application will become more common.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED; AXTEN, Jeffrey M.; MEDINA, Jesus Raul; WO2015/136463; (2015); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthetic Route of 1337532-51-0 , The common heterocyclic compound, 1337532-51-0, name is 5-Bromo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine, molecular formula is C7H7BrN4, 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 stirred solution of 1-(4-bromo-3-fluorophenyl)-3-(2,5-difluorophenyl)pyrrolidin-2-one (0.3 g, 0.8 mmol, 1.0 equiv ) in 1 ,4-dioxane (20 mL) was added bis(pinacolato)diboron (0.24 g, 1.0 mmol, 1.2 equiv) and potassium carbonate (0.33 g, 2.4 mmol, 3.0 equiv). The reaction mixture was degassed with N2 for 15 minutes, PdCl2(dppf)-CH2Cl2 adduct (0.033 g, 0.04 mmol, 0.05 equiv) was added and the reaction mixture was stirred for 3 hours at 100 C in a sealed tube. The reaction was cooled to room temperature, 5-bromo-7- methyl-7/-/-pyrrolo[2,3-c]pyrimidin-4-amine (0.27 g, 1.2 mmol, 1.5 equiv) and saturated aqueous NaHC03 (10 mL) were added, and N2 gas was bubbled through the mixture for 10 minutes. PdCl2(dppf)-CH2Cl2 adduct (0.033 g, 0.040 mmol, 0.05 equiv) was added, the vessel was sealed, and the reaction mixture was stirred at 100 C for 16 h. The reaction mixture was diluted with water (30 mL) and extracted with ethyl acetate (2 x 20 mL). The organics were combined and dried over Na2S04, filtered, and concentrated in vacuo to get crude compound. Crude product was purified by flash chromatography on silica gel and compound was eluted with 3% MeOH/DCM. The fractions containing the desired product were combined and concentrated to afford 1-4-(4-amino-7-methyl-7/-/-pyrrolo[2,3- d]pyrimidin-5-yl)-3-fluorophenyl)-3-(2,5-difluorophenyl)pyrrolidin-2-one (20 mg, 5.6 %) as off white solid. LCMS (ES) m/z = 438.3 [M+H]+. H NMR (400 MHz, DMSOd6) delta ppm 2.21 – 2.31 (m, 2 H), 3.74 (s, 3 H), 3.97 (t, J=7.6 Hz, 2 H), 4.20 – 4.30 (m, 1 H), 5.98 (br s,2 H), 7.18 – 7.22 (m, 1 H), 7.27 – 7.31 (m, 3 H), 7.39 – 7.45 (m, 1 H), 7.59 (d, J=8.4 Hz, 1 H), 7.81 (d, J=11.6 Hz, 1 H), 8.14 (s, 1 H).

The synthetic route of 1337532-51-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED; AXTEN, Jeffrey M.; MEDINA, Jesus Raul; WO2015/136463; (2015); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Related Products of 1337532-51-0, 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. 1337532-51-0, name is 5-Bromo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine. A new synthetic method of this compound is introduced below.

To a mixture of 1-(4-bromo-3-methylphenyl)-3-(3,5-difluorophenyl)pyrrolidin-2-one (0.6 g, 1.6 mmol, 1.0 equiv), bis(pinacolato)diboron (0.41 g, 1.6 mmol, 1.0 equiv), and potassium carbonate (0.48 g, 4.9 mmol, 3.0 equiv) was added 1 ,4-dioxane (10 ml_), and the mixture was degassed with Ar gas for 10 minutes. PdCI2 (dppf)-CH2Cl2 adduct (0.1 1 g, 0.08 mmol, 0.05 equiv) was added and degassed with Ar for 10 minutes. The reaction mixture was stirred for 3 h at 100 C in a sealed vessel. After consumption of SM, the reaction mixture was cooled to room temperature. 5-bromo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (0.37 g, 1.6 mmol, 1.0 equiv) and saturated aqueous NaHC03 (12 ml_) were added and degassed with argon for 10 min. PdCl2(dppf)-CH2Cl2 adduct (0.1 1 g, 0.08 mmol, 0.05 equiv) was added, the vessel was sealed, and the reaction mixture was stirred overnight at 100C. After consumption of SM, the reaction mixture was poured onto water and extracted with ethyl acetate (2 x 30 ml_). The combined organic layers were washed with brine solution (30 ml_), dried over Na2S04 and evaporated the solvent under reduced pressure to afford the crude product. The crude product was purified by flash column chromatography with 100 – 200 silica gel (24g column) and eluted with 3% MeOH in DCM mobile phase to afford the titled product 1-(4-(4-amino-7-methyl-7/-/-pyrrolo[2,3- d]pyrimidin-5-yl)-3-methylphenyl)-3-(3,5-difluorophenyl)pyrrolidin-2-one (0.1 g, 14%) as off white solid. LCMS (ES) m/z = 434.2 [M+H]+. H NMR (400 MHz, DMSO-d6) delta 2.21 – 2.27 (m, 4H), 2.54 – 2.61 (m, 1 H), 3.73 (s, 3 H), 3.93 – 4.07 (m, 3H), 5.54 (br, 2 H), 7.10 – 7.15 (m, 4 H), 7.25 (d, J=8.0 Hz, 1 H), 7.60 – 7.68 (m, 2 H), 8.13 (s, 1 H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,1337532-51-0, its application will become more common.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED; AXTEN, Jeffrey M.; MEDINA, Jesus Raul; WO2015/136463; (2015); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia