Reference of 1311265-74-3, A common heterocyclic compound, 1311265-74-3, name is 1-Bromo-3-cyclopropyl-5-fluorobenzene, molecular formula is C9H8BrF, 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.
Step B: A resealable glass pressure tube was charged with 2′-amino-l’,2,2-trimethyl-6-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)spiro[chroman-4,4′-imidazol]-5′( H)-one (50 mg, 0.13 mmol), 1- bromo-3-cyclopropyl-5-fluorobenzene (28 mg, 0.13 mmol), dichloro[l,l’- bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (5.3 mg, 0.0065 mmol), 20% aqueous Na2C03 (241 mu, 0.45 mmol), and 1 ,4-dioxane (1.3 mL, 0.13 mmol). The reaction mixture was sparged with N2 for 5 minutes, capped, and stirred at 90C for 90 minutes and allowed to cool to room temperature. The mixture was then diluted with EtOAc (10 mL) and washed with water (2 mL). The organic layer was separated, dried (MgSC^), filtered and concentrated in vacuo. The residue obtained was passed through a silica plug eluting with 5% MeOH/DCM to provide the semi pure product. This was then purified by preparative TLC eluting with 7% MeOH/DCM. The product isolated was filtered through a 45 muMu filter and concentrated in vacuo. The residue obtained was crystallized from DCM/Et20 to provide 2′-amino-6-(3-cyclopropyl-5-fluorophenyl)-r,2,2-trimethylspiro[chroman-4,4′-imidazol]- 5′(l’H)-one (14 mg, 0.036 mmol, 27% yield) as a solid. NMR (400 MHz, CDC13) delta 7.36 (d, J=8.61 Hz, 1H), 6.95 -6.87 (m, 4H), 6.63 (d, J=10.96Hz, 1H), 3.19 (s, 3H), 2.56 (d, J=13.03 Hz, 1H), 1.97 (d, J=14.08Hz, 1H), 1.94-1.88 (m, 1H), 1.52 (s, 3H), 1.41 (s, 3H), 1.02-0.97 (m, 2H), 0.73-0.69 (m, 2H); LCMS (APCI+) m/z 394 (M+H)+. Example 79 3-(2′-amino-1^2,2-trimethyl-5′-oxo-r,5′-dihydrospiro[chroman-4,4′-imidazole]-6-yl)-5- bromobenzonitrile
The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.
Reference:
Patent; ARRAY BIOPHARMA INC.; HUNT, Kevin, W.; RIZZI, James, P.; COOK, Adam; WO2011/72064; (2011); A1;,
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