The Synthetic Routes of 6-CHLORO-3-IODOIMIDAZO[1,2-B]PYRIDAZINE

6-Chloro-3-iodoimidazo[1,2-b]pyridazine is an important pharmaceutical intermediate that is used in the synthesis of several anti-bacterial and anti-fungal agents.
The synthesis of this compound can be achieved through several methods, each of which has its own advantages and disadvantages.
In this article, we will discuss some of the most commonly used synthetic routes for the preparation of 6-chloro-3-iodoimidazo[1,2-b]pyridazine.

Route 1: via N-Allyl derivatization

One of the most common and straightforward methods for the synthesis of 6-chloro-3-iodoimidazo[1,2-b]pyridazine involves the N-allylation of N-methylpyrrole-2-carboxamide followed by an electrophilic substitution reaction with chlorine gas.
The reaction scheme is shown below:

N-Methylpyrrole-2-carboxamide     N-Allyl derivative
  |                                    |
  |       N-Chlorosuccinimide (NCS)   N-Allyl chloride (allyl Cl)
  |                                    |
  |                          water or ether
  |                                    |
  |                   (i) 2NH3   (ii) Pt/C
  |                                    |
  |        H2N-C-C(=N)-C-C(=O)-NH2  Pt

In this route, N-methylpyrrole-2-carboxamide is first converted to its N-allyl derivative by reaction with allyl chloride in the presence of a Lewis acid catalyst, such as N-chlorosuccinimide (NCS).
The N-allyl derivative is then treated with chlorine gas in the presence of a reducing agent, such as hydrogen gas or platinum black, to form the N-chlorinated derivative.
The final product is obtained by reduction of the N-chlorinated derivative with hydrogen gas in the presence of a metal catalyst, such as platinum.

Route 2: via Pd/C-promoted condensation

Another synthetic route for the preparation of 6-chloro-3-iodoimidazo[1,2-b]pyridazine involves the Pd/C-promoted condensation of 2-chloro-4-nitro-6-phenylpyrimidine with N-methylpyrrole-2-carboxamide.
The reaction scheme is shown below:

2-Chloro-4-nitro-6-phenylpyrimidine N-Methylpyrrole-2-carboxamide Pd/C
  |                                     |
  |       HCl + N2  H2N-C-C(=N)-C-C(=O)-NH2
  |                                     |
  |        2NH3        Pd/C
  |                                     |
  |         Pt    H2  H2  H2