RARECHEM AL BO 0496 synthesis

Yield:42783-81-3 41%

Reaction Conditions:

with dmap;N-ethyl-N,N-diisopropylamine;N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate in tetrahydrofuran;N,N-dimethyl-formamide at 20; for 16 h;

Steps:

3-(Dimethylamino)-3-oxopropanoic acid:

To a stirred solution of 3-tert-butoxy-3-oxopropanoic acid (680 mg, 4.25 mmol) and Me₂NH (2M in THF, 3.18 mL, 6.37 mmol) in DMF (10 mL) was added N,N-diisopropylethylamine (2.224 mL, 12.74 mmol), DMAP (104 mg, 0.849 mmol) and HATU (2421 mg, 6.37 mmol) and the resulting mixture stirred at room temperature for 16 h. H₂O was added and the mixture extracted with EtOAc (2 x 50 mL), the extracts were washed with 1N HCl (20 mL), dried (Na₂SO₄), filtered and concentrated to give crude product which was dissolved in CH₂Cl₂ (5.00 mL) and treated TFA (4.91 mL, 63.7 mmol). The mixture was stirred at room temperature for 16h before the solvent was removed under reduced pressure to afford 230 mg (41%) of the desired product as light yellow solid that was used in the next step without further purification. ¹H NMR (500 MHz, DMSO-d₆) d ppm 12.1 (1 H, br s), 3.4 (2 H, s), 2.9 (3 H, s), 2.8 (3 H, s). LCMS (M+H)+= 132.33

References:

Patel, Manoj;Naidu, B. Narasimhulu;Dicker, Ira;Higley, Helen;Lin, Zeyu;Terry, Brian;Protack, Tricia;Krystal, Mark;Jenkins, Susan;Parker, Dawn;Panja, Chiradeep;Rampulla, Richard;Mathur, Arvind;Meanwell, Nicholas A.;Walker, Michael A. [Bioorganic and Medicinal Chemistry,2020,vol. 28,# 13,art. no. 115541] Location in patent:supporting information