Analyzing the synthesis route of 183208-22-2

At the same time, in my other blogs, there are other synthetic methods of this type of compound,183208-22-2, 5-Bromo-1-methyl-1H-pyrrolo[2,3-b]pyridine, and friends who are interested can also refer to it.

With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.183208-22-2, name is 5-Bromo-1-methyl-1H-pyrrolo[2,3-b]pyridine, molecular formula is C8H7BrN2, molecular weight is 211.06, as common compound, the synthetic route is as follows.SDS of cas: 183208-22-2

To a solution of tert-butyl (S)-2-(methoxymethyl)pyrrolidine-1-carboxylate (663 mg, 3.08mmol) in DCM (10 mL) was added trifluoroacetic acid (1.76 g, 15.40 mmol) within 5 min at0C. The mixture was warmed up to room temperature within 2 h and carefully poured into a10% NaOH solution (60 mL). After extraction with DCM (2 × 50 mL) the combined organicphases were dried over MgSO4, and evaporated. The residue was dissolved in DCM (5 mL)and N,N-diisopropylethylamine (521 mg, 4.03 mmol) was added at room temperature. Thissolution containing the deprotected pyrrolidine was then stirred until it was needed.A two-neck flask was charged with 5-bromo-1-methyl-1H-pyrrolo[2,3-b]pyridine (3)(500 mg, 2.37 mmol) and dry THF (30 mL) under argon. The solution was cooled to -80 C inan ethanol/nitrogen cooling bath and t-BuLi (1.4 M in pentane, 1.69 mL, 2.37 mmol) wasS 6added dropwise. The reaction mixture was warmed up to -75 C within 10 min and transferredto a solution of DABCO-bis(sulfur dioxide) (569 mg, 2.37 mmol) in dry THF (15 mL) at -75C. The cooling bath was removed after 30 min and the reaction mixture warmed up to roomtemperature. The THF solvent was removed under reduced pressure and dry DCM (20 mL)was added. N-Chlorosuccinimide (379 mg, 2.84 mmol) was slowly added as a solution in dryDCM (5 mL) followed by dropwise addition of the deprotected pyrrolidine. After the additionof water (35 mL) the mixture was extracted with DCM (2 × 20 mL). The combined organicphases were dried over MgSO4, and evaporated. Column chromatographic purification (SiO2,CH/EtOAc, 2:1) yielded a colorless, crystalline solid [291 mg, 40% yield].MP: 66 – 67 C (CH/EtOAc).1H-NMR (300 MHz, CDCl3): delta = 1.50-1.60 (m, 2H, 13-CHa, 14-CHa), 1.79-1.89 (m, 2H,13-CHb, 14-CHb), 3.08-3.18 (m, 1H, 15-CHa), 3.34-3.42 (m, 1H, 16-CHa), 3.38 (s, 3H,18-CH3), 3.44-3.52 (m, 1H, 15-CHb), 3.68 (dd, 2JH,H = 9.2 Hz, 3JH,H = 3.8 Hz, 1H, 16-CHb),3.71-3.81 (m, 1H, 12-CH), 3.95 (s, 3H, C-19), 6.60 (d, 3JH,H = 3.5 Hz, 1H, 3-CH), 7.33 (d,3JH,H = 3.5 Hz, 1H, 2-CH), 8.39 (d, 4JH,H = 2.1 Hz, 1H, 4-CH), 8.80 (d, 4JH,H = 2.1 Hz, 1H,6-CH) ppm.13C-NMR (75 MHz, CDCl3): delta = 24.1 (t, C-14), 28.9 (t, C-13), 31.7 (q, C-19), 49.5 (t, C-15),59.1 (q, C-18), 59.3 (d, C-12), 75.3 (t, C-16), 101.2 (d, C-3), 119.7 (s, C-9), 125.7 (s, C-5),129.0 (d, C-2), 131.7 (d, C-4), 142.0 (d, C-6), 149.0 (s, C-8) ppm.ESI(+)-MS: calcd. for C14H19N3O3S + H+, 310.1220; found 310.1220.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,183208-22-2, 5-Bromo-1-methyl-1H-pyrrolo[2,3-b]pyridine, and friends who are interested can also refer to it.

Reference:
Article; Waldmann, Christopher M.; Hermann, Sven; Faust, Andreas; Riemann, Burkhard; Schober, Otmar; Schaefers, Michael; Haufe, Guenter; Kopka, Klaus; Bioorganic and Medicinal Chemistry; vol. 23; 17; (2015); p. 5734 – 5739;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem