1-(5-BROMOPYRIMIDIN-2-YL)PIPERIDINE-4-CARBOXYLIC ACID synthesis

Yield: 99%

Reaction Conditions:

with triethylamine in 1,4-dioxane;water at 20; for 18 h;

Steps:

101.1
Step 7: Preparation of 3-(3-((tert-butoxycarbonyl)amino)phenyl)propanoic acid. [0639] To a solution of 3-(3-aminophenyl)propanoic acid (850 mg, 5.15 mmol), TEA (1.4 mL, 10.3 mmol), H2O (7 mL) in dioxane (14 mL) was added B0C2O (1.8 mL, 7.72 mmol) at 20 °C. Reaction mixture was allowed to stir for 18 h. The colorless solution became yellow gradually. LCMS is 95% (RT=0.759 min; MS Calc'd: 265.1; MS Found: 288.1 [M+Na]⁺). 1,4- dioxane was removed under reduced pressure and HC1 solution (5 mL, 2 M) was added drop- wise. After addition of H2O (40 mL), the mixture was extracted with DCM (20 mL x3). The organic layer was dried over anhydrous Na2SCh. and concentrated to afford 3-(3-((tert- butoxycarbonyl)amino)phenyl)propanoic acid (1.36 g, yield: 99%) as an off-white solid. NMR (400 MHz, CDCb) d 1.52 (9H, s), 2.68 (2H, t, J= 8.0 Hz), 2.93 (2H, t, J= 8.0 Hz), 6.57 (1H, s), 6.89 (1H, d, J= 7.6 Hz), 7.12-7.24 (2H, m), 7.28 (1H, br s).

References:

PETRA PHARMA CORPORATION;LINDSTRÖM, Johan;PERSSON, Lars Boukharta;VIKLUND, Jenny;KESICKI, Edward A.;HICKEY, Eugene R.;DAHLGREN, Markus K.;GERASYUTO, Aleksey I. WO2019/126731, 2019, A1 Location in patent:Paragraph 0639