Some common heterocyclic compound, 627871-16-3, name is 5-Bromo-4-fluoro-2-methylaniline, molecular formula is C7H7BrFN, 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. Quality Control of 5-Bromo-4-fluoro-2-methylaniline
(1 ‘-bis(diphenylphosphino)ferrocene)-dichioropalladium(il) (234 mg, 0,286 mmol), phenylboronic acid (907 mg, 7.44 mmol) and 5-bromo-4-fluoro-2-methylaniline (1.17 g, 5.72 mmol) were dissolved in DME (10 ml). Sodium carbonate aq 2M (5.7 mL, 1 1 mmol) was added, and the mixture was irradiated with microwaves for 2h at 120C. After removing the DME under reduced pressure, the residue was taken with AcOEt (15 mL) and washed with brine (2 x 10 mL). The organic layer was concentrated under reduced pressure and the residue was purified by semi-preparative HPLC-UV, to afford 6-fluoro-4-methyl-[1 ,1 ‘-biphenyl]-3-amine (812 mg, Y = 70%) as a dark oil. MS (ESI+) m/z: 202.1 [M+H]+. (0152) Starting from 6-fluoro-4-methyl-[1 , 1 ‘-biphenyl]-3-amine (751 mg, 3.73 mmol), 3- bromo-N-(6-fluoro-4-methyl-[1 ,1’-biphenyl]-3-yl)benzenesulfonamide was synhesized as described in Procedure B, affording a mixture of mono- and di-sulfonamide, which by hydrolysis with NaOH aq/Dioxane was completely converted to the mono- sulfonamide (1 .41 g, Y = 89%). MS (ESI+) m/z: 442.0 [M+Na]+. (0153) The sulfonamide (1 .03 g, 2.46 mmol) was then coupled with hept-6-ynoic acid (0.63 mL, 4.92 mmol) as described in Procedure B, to afford 7-(3-(N-(6-fluoro-4-methyl- [1 ,1 ‘-biphenyl3-3-yl)sulfamoyl)phenyl)hept-6-ynoic acid (290 mg, Y = 25%). MS (ES+) m/z: 466.2 [M+H]+. (0154) Compound 9 was then obtained by reduction of the alkyne derivative (290 mg, 0.623 mmol) as described for compound 2, as a white solid (235 mg, Y = 80%). 1H NMR (300 MHz, CHLOROFORM-cf) delta ppm 1.20 – 1.33 (m, 4 H) 1 .47 – 1.59 (m, 4 H) 2.01 (s, 3 H) 2.31 (t, J=7.34 Hz, 2 H) 2.58 (t, J=7.56 Hz, 2 H) 6.88 (d, J=10.96 Hz, 1 H) 7.00 (s, 1 H) 7.27 (d, J=7.45 Hz, 1 H) 7.32 – 7.43 (m, 7 H) 7.51 – 7.60 (m, 2 H). MS (ESI+) m/z: 470.2 [M+H]+.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 627871-16-3, its application will become more common.
Reference:
Patent; DOMPE’ FARMACEUTICI S.P.A.; DE PIZZOL, Maria; SIRICO, Anna; ZIPPOLI, Mara; BIANCHINI, Gianluca; BECCARI, Andrea; ARAMINI, Andrea; LIBERATI, Chiara Rossana Maria; (53 pag.)WO2018/29150; (2018); A1;,
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