Application of 13472-59-8 ,Some common heterocyclic compound, 13472-59-8, molecular formula is C6H6BrNO, 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.
Pd2(dba)3 (38.1 mg, 0.042 mmol) and DavePhos (24.6 mg, 0.062 mmol) are added to a N2 purged solution of [7-tert-butyl-5-(4-chloro-3-fluoro-phenyl)furo[3,2-b]pyridin-2-yl]-(2,2- dimethylpiperazin-1-yl)methanone (Hydrochloride salt) (llntermediate D) (100 mg, 0.208 mmol), 3-bromo-2-methoxy-pyridine (39.2 mg, 0.208 mmol) and sodium tert-butoxide (219 iL of 2.0 M,0.437 mmol) in THE. The reaction is stirred in a sealed tube at 100 C for 3 hours. At room temperature, water is added along with dichloromethane and the phases are separated using a phase separator cartridge. The organic phase is then filtrated through a pre-packed Celite pad with DCM and concentrated under vacuum. The crude residue is dissolved in NMP and purified on a Gemini-NX 250-21 column (Isco Combiflash EZ PREP) eluting with 65-100% CH3CN (0.1% Formic Acid)/Water (0.1% Formic Acid) over 30 minutes. Selected fractions are combined and lyophil ized to give [7-tert-butyl-5-(4-chloro-3-fluoro-phenyl)furo [3,2-b] pyridin-2-yl]-[4-(2-methoxy-3-pyridyl)-2,2-dimethyl-piperazin-1-yl]methanone (20.6 mg, 17%) as a yellow solid.ESI-MS m/z calc. 550.2147, found 551.26 (M+1)+; Retention time: 3.37 using Method B. 1H NMR(400 MHz, DMSO-d6) 6 8.18 (dd, J = 11.0, 2.0 Hz, 1H), 8.04 (dd, J = 8.4, 2.0 Hz, 1H), 7.84 (s, 1H),7.77 – 7.69 (m, 2H), 7.56 (s, 1H), 7.22 – 7.15 (m, 1H), 6.93 (dd, J = 7.6, 4.9 Hz, 1H), 3.89 (s, 3H),3.84 – 3.76 (m, 2H), 3.30 – 3.23 (m, 2H), 3.11 (s, 2H), 1.57 (s, 6H), 1.54 (s, 9H).
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. 13472-59-8, 3-Bromo-2-methoxypyridine, other downstream synthetic routes, hurry up and to see.
Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; LIU, Bingcan; DORICH, Stephane; DE LESELEUC, Mylene; DUPONT-GAUDET, Kristina; JAMES, Clint, Alwyn; VAILLANCOURT, Louis; BEAULIEU, Marc-Andre; STURINO, Claudio; (236 pag.)WO2018/57588; (2018); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem