Extended knowledge of 366-99-4

Electric Literature of 366-99-4, A common heterocyclic compound, 366-99-4, name is 3-Fluoro-4-methoxyaniline, molecular formula is C7H8FNO, 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.

5-bromo-2-chloro-N-phenylnicotinamide (224 mg, 719 mumol) and 3-fluoro-4- methoxybenzenamine (316.7 mg, 2244 mumol) were suspended in isoamyl alcohol (1.5 ml) in a reaction microwave vessel which was sealed. This vessel was heated in the Biotage Initiator microwave at 200 0C for 20 minutes, with 45 seconds of stirring beforehand, and then cooled to room temperature. This process was repeated using 5-bromo-2-chloro-N-phenylnicotinamide (810 mg, 2.60 mmol) and 3-fiuoro-4- methoxybenzenamine (1.092 g, 7.74 mmol), and isoamyl alcohol (7.5 ml), and then repeated a third time with 5-bromo-2-chloro-N-phenylnicotinamide (1.643 g, 5.28 mmol), 3-fluoro-4-methoxybenzenamine (2.285 g, 16 mmol), and isoamyl alcohol (10 ml). These three sets of reaction were combined, concentrated, treated with Et2psi, and filtered. The solid was washed with Et2O, and the filtrate was concentrated and purified on a silica gel filter (~3 inches, DCM) to afford the desired 5-bromo-2-(3-fluoro-4- methoxyphenylamino)-N-phenylnicotinamide (3.49 g, 8.39 mmol, 75percent yield). MS (ESI pos. ion) m/z: 416 (MH+, 79Br), 418 (MH+, 81Br). Calc’d exact mass for C19H15BrFN3O2: 415 (79Br), 417 (81Br).

The synthetic route of 366-99-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AMGEN INC.; WO2008/79294; (2008); A1;,
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