The synthetic route of 5,7-Dichloropyrido[3,4-b]pyrazine has been constantly updated, and we look forward to future research findings.
These common heterocyclic compound, 1379338-74-5, name is 5,7-Dichloropyrido[3,4-b]pyrazine, 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. Computed Properties of C7H3Cl2N3
Intermediate 37: 1 ,1 -dimethylethyl 3-{r(7-chloropyridor3,4-fllpyrazin-5- yl)amino1methyl)-4,4-difluoro-1 -piperidinecarboxylate (Isomer 2); 5,7-Dichloropyrido[3,4-b]pyrazine (620mg, 3.10mmol) was dissolved in N-methyl-2- pyrrolidinone (NMP) (5mL) and to this was added DIPEA (0.601 ml_, 4.65mmol) and 1 , 1-dimethylethyl 3-(aminomethyl)-4,4-difluoro-1-piperidinecarboxylate (776mg, 3.10mmol). This was heated in a microwave at 130C for 30min. The reaction mixture was partitioned between ethyl acetate and water. The aqueous was re-extracted twice with ethyl acetate and the combined organic layers washed with brine, dried over a hydrophobic frit and concentrated in vacuo to yield a brown oil. It was dissolved in DCM and passed through silica (100g) eluting with a 10-50% ethyl acetate in cyclohexane gradient. Appropriate fractions were combined and concentrated in vacuo to yield the title compound as a yellow solid, 1.0g.Chiral separation was achieved (Sample preparation: Sample dissolved in ethanol (30ml) sonicating and heating with air gun as required. 4-5ml injections were then pumped onto a preparative scale Whelk-0 (S, S) column (2 inch). Details as follows: Column – Whelk-0 (S, S) (50x250mm, l Omicron); Detection – UV DAD – 300nm (bandwidth 180nm, reference 550nm (bandwidth 100nm)); Flow Rate – 70ml/min; Mobile Phase A: Heptane; Mobile Phase B: I PA; Isocratic method (premixed) 5% B; Runtime – 60min; Number of runs – 8) to yield the title compound (second eluting peak from the chiral column) as a yellow solid (441 mg).LCMS (Method B): Rt =1.27min, MH+ =414 The following intermediate was obtained as the first eluting peak from the chiral separation above:; Intermediate 38: 1 ,1 -dimethylethyl 3-{r(7-chloropyridor3,4-fllpyrazin-5- yl)amino1methyl)-4,4-difluoro-1 -pipendinecarboxylate (Isomer 1); LCMS (Method B): Rt =1.27min, MH+ =414The following intermediate was prepared similarly:Intermediate 39: 1 ,1 -dimethylethyl 5-{r(7-chloropyridor3,4-fllpyrazin-5-LCMS (Method B): Rt =1.24min, MH+= 414
The synthetic route of 5,7-Dichloropyrido[3,4-b]pyrazine has been constantly updated, and we look forward to future research findings.
Reference:
Patent; GLAXO GROUP LIMITED; ATKINSON, Francis Louis; ATKINSON, Stephen John; BARKER, Michael David; DOUAULT, Clement; GARTON, Neil Stuart; LIDDLE, John; PATEL, Vipulkumar Kantibhai; PRESTON, Alexander G; SHIPLEY, Tracy Jane; WILSON, David Matthew; WATSON, Robert J; WO2012/123312; (2012); A1;,
Pyrazine – Wikipedia,
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