Related Products of 50846-36-1,Some common heterocyclic compound, 50846-36-1, name is 2-Amino-2-methylpropanenitrile hydrochloride, molecular formula is C4H9ClN2, 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.
2 M Lithium hydroxide (175 mL, 350 mmol, 10 equiv) was added to a solution of compound 27 (17.1 g, 35 mmol, 1 equiv) in THF (350 mL). The reaction mixture was stirred overnight at room temperature, at which point LC/MS indicated all the starting (0509) material was consumed. In addition to the desired product, ~20% of compound 28(b) (loss of benzenesulfonyl group) was also present. The reaction was poured into 1N HCl (0.5 L) and extracted with ethyl acetate (1 L). The organic layer was separated and concentrated under reduced pressure to give a crude mixture of compound 28(b) and compound 28(a), which were used subsequently. [0250] Step 5 – N-(2-Cyanopropan-2-yl)-6-(2-(6-fluoropyridin-3-yl)-1-(phenylsulfonyl)- 1H-pyrrolo[2,3-b]pyridin-5-yl)picolinamide (30): N,N’-diisopropylethylamine (14.1 mL, 81 mmol, 4 equiv) was added to a solution of the ~1 to 4 mixture of compound 28(b) and compound 28(a) (9.6 g, 20.23 mmol, 1 equiv) in DMF (135 mL). 2-Amino-2- methylpropanenitrile hydrochloride (3.7 g, 30.4 mmol, 1.5 equiv) was added and the reaction was stirred for ~30 minutes at room temperature. Propylphosphonic anhydride (T3P, 50 wt% in ethyl acetate) (23.8 mL, 40.5 mmol, 2 equiv) was added dropwise, with the internal temperature gradually increasing from 20 to 30 C during the addition. After stirring overnight, LC/MS indicated ~50% conversion of starting material. Stirring an additional 24 hours resulted in no further conversion. The reaction mixture was poured into water (1 L) and extracted with ethyl acetate (500 mL). The organic layer was separated, washed with saturated brine (500 mL) and concentrated under reduced pressure. The crude solid was dissolved in THF, dry-loaded onto silica gel and purified on an AnaLogix column (80 g), eluting with a gradient of 0 to 50% ethyl acetate in dichloromethane. The resulting solid was triturated with MTBE (15 mL) to give N-(2- cyanopropan-2-yl)-6-(2-(6-fluoropyridin-3-yl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-5- yl)picolinamide.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Amino-2-methylpropanenitrile hydrochloride, its application will become more common.
Reference:
Patent; PLEXXIKON INC.; ZHANG, Chao; WU, Guoxian; SPEVAK, Wayne; GUO, Zuojun; ZHANG, Ying; (138 pag.)WO2018/226846; (2018); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts