hydroxychloroquine (HCQ) Synthesis: Which mechanism?


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> Draw the product of the following reaction and provide an explanation for this reaction knowing that $\mathrm{ROH}$ or $\mathrm{RNH\_2}$ + $\mathrm{PhCl}$ do not react at all.
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> [![enter image description here](https://i.stack.imgur.com/Gxrkg.png)](https://i.stack.imgur.com/Gxrkg.png)
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I have no doubt that the answer is hydroxychloroquine (HCQ), but how would it be formed if the reaction:
$\mathrm{RNH\_2}$ + $\mathrm{PhCl}$
does not happen? Or, is the question hinting that the reaction takes the $\mathrm{S\_N1}$ pathway where the phenylcation gets formed? If so, why does the Cl atom para to the nitrogen leave more readily than the other Chloride?




The 2 and 4 positions of quinolines are similar to the 2 and 4 positions of pyridine in reactivity. 2 and 4 haloquinolines/pyridines are highly reactive to nucleophiles by SNAr. Indeed 4-Cl-pyridine has to be handled as the hydrochloride because of its propensity to self condense. 


The 7 position, by contrast, is unactivated and similar in reactivity to benzenes, so the 7-Cl is not going to undergo SNAr without specialist catalysis. 


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