Electric Literature of 171178-46-4 , The common heterocyclic compound, 171178-46-4, name is 5-((tert-Butoxycarbonyl)amino)-2-chloroisonicotinic acid, molecular formula is C11H13ClN2O4, 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-((fe/f-butoxycarbonyl)amino)-2-chloroisonicotinic acid (Intermediate B) (4.27 g, 15 mmol, 1 equiv.) was added to a 500 mL two necked oven-dried round bottom flask equipped with a stirring bar and suspended in dichloromethane (187 mL, 0.08M) was added. 4-Dimethylamino pyridine (7.40 g, 60 mmol, 4 equiv.) was added at 22C resulting in an homogeneous solution. /V-(3-dimethylaminopropyl)-/V-ethylcarbodiimide (4.65 g, 30 mmol, 2 equiv.) was added at that temperature and the crude mixture was stirred for 3 h. Anhydrous MeOH (HPLC quality), (5.5 mL, 135 mmol, 9 equiv.) was added to the solution and the mixture was stirred for 1 h at 22C. The resulting mixture was heated to reflux using an aluminium heating block for 72 h. TLC (EtOAc:MeOH 90:10 %v/v) showed complete conversion of Intermediate B into Intermediate C. The reaction was permitted to reach to 22C and volatiles were removed under reduced pressure. Dichloromethane (150 mL) was added to the residue until complete solution was achieved and the mixture was transferred to a separating funnel, washed with H2O (1 x 70 mL), HCI 1 M (2 x 50 mL) and saturated NaCI solution (1 x 50 mL). The organic phase was dried with Na2S04 and filtered through a pad of Na2S04 on a filter plate. The solvent was removed under reduced pressure giving a brown solid, which was purified by automated flash chromatography (Heptane:EtOAc, product elution with EtOAc 100%v/v) giving methyl 5-((fe/f-butoxycarbonyl)amino)-2-chloroisonicotinate as a pale yellow solid (4.04 g, 79% yield). Purity: 99.4% (UPLC-A); mp: 90.0-95.8 C; 1H- NMR (CDCI3), 5(ppm): 9.68 (bs, NH), 9.49 (s, 1 H), 7.73(s, 1 H), 7.20 (s, 1 H), 3.91 (s, 3H), 1.47 (s, 9H); LR-MS (ESI+): m/z= 287.1 Da [M+H]+, calcd. for CI2HI5CIN204: 286.2
The synthetic route of 171178-46-4 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; FAES FARMA, S.A.; HERNANDEZ HERRERO, Gonzalo; GARCIA DOMINGUEZ, Neftali; ZAZPE ARCE, Arturo; OLIVERA TIZNE, Roberto; NOVERGES PEDRO, Barbara; CORCOSTEGUI VIVAR, Reyes; TATO CERDEIRAS, Paloma; (124 pag.)WO2020/20939; (2020); A1;,
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