Reference of 206551-41-9, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 206551-41-9 name is Methyl 3-bromo-2-fluorobenzoate, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.
Step 1: Methyl 3-((2-chloro-5-(1 ,4-dimethyl- 1H-1 ,2,3-triazol-5-yl)pyridin-3- yl)amino)-2-fluorobenzoateTo a 70 mL pressure vial containing 2-chloro-5-(1,4-dimethyl-1H-1,2,3-triazol-5- yl)pyridin-3-amine (Step 1 of Example 54, 500 mg, 2.24 mmol), methyl 3-bromo-2-fluorobenzoate (Oakwood, 781 mg, 3.35 mmol) and Cs2CO3 (728 mg, 2.24 mmol) in dioxane (10 mL) was added 1,1 ?-bis(diphenylphosphino)ferrocene (62.0 mg, 0.11 mmol), Pd(OAc)2 (85 mg, 0.38 mmol) and Xantphos (65 mg, 0.11 mmol). N2 was bubbled through the reaction mixture for 2 mm. The vial was sealed and heated to 100 °C for 24h. BrettPhos precatalyst (100 mg, 0.12 mmol) and additional methyl 3-bromo-2-fluorobenzoate (781 mg, 3.35 mmol) were added. N2 was bubbled through the reactionmixture for 2 mm, and then heating was continued at 110 °C for 24 h. Additional BrettPhos precatalyst (100 mg, 012 mmol) was added and stirring was continued at 120°C for 5 h. BrettPhos precatalyst (100 mg, 0.12 mmol) was again added and the reaction mixture was heated at 120 °C for 5 h. After cooling to room temperature, the mixturewas diluted with CHC13 and filtered through Celite® rinsing with CHC13. The filtrate was concentrated and purified using ISCO silica gel chromatography (40 g column, gradient from 0percent to 100percent EtOAc/CH2C12) to give the title compound (140 mg, 17percent) as a white solid. ?H NMR (400 MHz, CDC13) oe 7.90 (d, J=2.1 Hz, 1H), 7.74 (ddd, J=8.0, 6.5, 1.7 Hz, 1H), 7.52 – 7.44 (m, 1H), 7.24 (d, J=0.9 Hz, 1H), 7.17 (t, J2.0 Hz, 1H), 6.34 (s, 1H),3.97 (d, J=0.7 Hz, 6H), 2.32 (s, 3H); LCMS (M+H) = 376.3; HPLC RT = 2.23 mm(Column: Chromolith ODS S5 4.6 x 50 mm; Mobile Phase A: 10:90 MeOH:water with0.1percent TFA; Mobile Phase B: 90:10 MeOH :water with 0.1percent TFA; Temperature: 40 °C;Gradient: 0-100percent B over 4 mm; Flow: 4 mL/min).
At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 3-bromo-2-fluorobenzoate, and friends who are interested can also refer to it.
Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; NORRIS, Derek J.; DELUCCA, George V.; GAVAI, Ashvinikumar V.; QUESNELLE, Claude A.; GILL, Patrice; O’MALLEY, Daniel; VACCARO, Wayne; LEE, Francis Y.; DEBENEDETTO, Mikkel V.; DEGNAN, Andrew P.; FANG, Haiquan; HILL, Matthew D.; HUANG, Hong; SCHMITZ, William D.; STARRETT, JR, John E.; HAN, Wen-Ching; TOKARSKI, John S.; MANDAL, Sunil Kumar; WO2015/100282; (2015); A1;,
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