2-Amino-4,6-dichloro-nicotinicacidmethylester Chemical Properties

Boiling point:

319.1±37.0 °C(Predicted)

Density 

1.506

storage temp. 

under inert gas (nitrogen or Argon) at 2–8 °C

pka

-0.40±0.50(Predicted)

Appearance

Light yellow to orange Solid

InChI

InChI=1S/C7H6Cl2N2O2/c1-13-7(12)5-3(8)2-4(9)11-6(5)10/h2H,1H3,(H2,10,11)

InChIKey

HJZKXHRUERDKKA-UHFFFAOYSA-N

SMILES

C1(N)=NC(Cl)=CC(Cl)=C1C(OC)=O

2-Amino-4,6-dichloro-nicotinicacidmethylester Usage And Synthesis

Uses

Methyl 2-Amino-4,6-dichloropyridine-3-carboxylate is used in preparation of macrocyclic broad spectrum antibiotics.

Synthesis

The general procedure for the synthesis of methyl 2-amino-4,6-dihydroxynicotinate from methyl 2-amino-4,6-dihydroxynicotinate is as follows: Step 116-2: Methyl 2-amino-4,6-dihydroxynicotinate (30 g), phosphorochloridic acid (150 ml) and N,N-diisopropylethylamine (30 ml) obtained in step 116-1 were mixed and the mixture was stirred at room temperature for 3 days. Upon completion of the reaction, the reaction mixture was concentrated, followed by azeotropic distillation with toluene 3 times to remove residual water. Methanol (30 ml) and water (150 ml) were slowly added to the residue under cooling in an ice bath and the mixture was continued to be stirred at room temperature for 1 hour. The resulting solid was collected by filtration and this solid was combined with the solid precipitated from the filtrate. Methanol (50 ml) was added to the combined solids and after stirring for 1 hour at room temperature, the solids were collected by filtration to give primary crystals. The filtrate was concentrated, methanol (10 ml) was added to the residue and the solid was again collected by filtration to obtain secondary crystals. Finally, the primary and secondary crystals were combined to afford the target compound methyl 2-amino-4,6-dichloronicotinate (21 g, 59% yield). 1H-NMR (DMSO-D6) δ: 3.84 (s, 3H), 6.84 (s, 1H), 7.16 (br s, 2H).

References

[1] Patent: US2011/77267, 2011, A1. Location in patent: Page/Page column 48
[2] Patent: US2008/188467, 2008, A1. Location in patent: Page/Page column 48
[3] Patent: WO2015/103355, 2015, A1. Location in patent: Paragraph 0213