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;,
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