It’s nowhere near as difficult to make as the article may imply, though. Yes, that first-generation route is quite a doozy, involving some harsh conditions (multiple steps at -78° C, which is actually not as difficult to carry out at the bench as it sounds) and nasty reagents, especially n-BuLi, which explodes into flames upon exposure to air. But it’s fairly easy to carry out on a small scale in a typical med chem lab. If you’re a medicinal chemist and need to make limited amounts, say, maybe in the hundreds of milligrams—which would probably be far more than enough to do preclinical studies—then that route will do. But it definitely can’t be scaled up easily to multi-thousand gallon chemical reactors, although like the article says, that’s where the process chemists come in. The second-generation route looks much better, and I’m sure it’s already being optimized even further.
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