Application of 705-09-9, These common heterocyclic compound, 705-09-9, name is 2-(Difluoromethyl)-1H-benzo[d]imidazole, 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.
Example 67 (R)-2-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-5-(4-(methylsulfonyl)benzyl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine A mixture of (R)-2-chloro-5-(4-(methylsulfonyl)benzyl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine (PREPARATION x10 50 mg, 0.127 mmol), 2-(difluoromethyl)-1H-benzo[d]imidazole (21.29 mg, 0.127 mmol), cesium carbonate (61.9 mg, 0.190 mmol), tris(dibenzylideneacetone)dipalladium(0) (4.64 mg, 5.06 mumol) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl (4.83 mg, 10.13 mumol) in DMF 253 muL was heated to 130 C. in a microwave for 40 minutes. Additional tris(dibenzylideneacetone)dipalladium(0) (4.64 mg, 5.06 mumol) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl (4.83 mg, 10.13 mumol) were added, and the reaction mixture was heated to 130 C. in a microwave for 1 hour. EtOAc and water were added and the mixture was filtered through Celite and extracted with EtOAc (2*). The combined extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO2-NH2, 30-100% EtOAc/hexane gradient) to afford the title compound as a yellow solid (14.3 mg, 21.4%). 1H NMR (400 MHz, CDCl3) delta 3.08 (s, 3H), 3.19-3.38 (m, 4H), 3.68 (td, J=12.00, 2.78 Hz, 1H), 3.83-3.92 (m, 1H), 3.94-4.02 (m, 1H), 4.11-4.20 (m, 1H), 4.44-4.63 (m, 3H), 7.36-7.75 (m, 6H), 7.93-8.01 (m, 3H), 8.17-8.23 (m, 1H). ESI-MS m/z [M+H]+ calc’d for C25H24F2N6O3S, 527.16. found 527.3.
The synthetic route of 705-09-9 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; US2012/220575; (2012); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem