Chemistry 301 Q1 September 12, 2017: Agenda Comments on 1st proposed synthesis assignment: for these “proposed synthesis” type assignments you only need complete schemes and reference; don’t need written out procedure or spectral data (make sure you have and have read ref though) Lecture: Synthesis updates, techniques, safety, notebook, med chem intro (time permitting) Lab today (1-4 pm): 1) NMR training with Jia, 2) train with Lincoln/Dora/Aron/Rob on anhydrous technique to set up your first reaction Next time in lecture: Continue (or start) talking med chem Due: proposed synthesis of your group’s targets Homework: work in lab with partner when you have time, start reactions early with partner, etc.

Synthesis updates! Synthesis is awesome!

Workgroup B Info Chemicals: Please check the molecule sign-up sheet for info on what chemicals Rob has now received – Rob will have the chemicals in Lab. Be sure to read and read again label to make sure you don’t take the wrong thing! Making the urea step 1, making the carbamate: Yes, the Mowbray paper is actually good for something (Scheme 3)! A) B) WuXi’s detailed synthesis: phenyl (3-(pyridin-2-yl)-1H-pyrazol-5-yl)carbamate (4). To a solution of compound 3 (50.00 g, 312.15 mmol, 1.00 eq) in pyridine (500.00 mL) was added phenyl carbonochloridate (58.65 g, 374.58 mmol, 1.20 eq)   drop-wise at 0°C over a period of 60 mins. Then the reaction mixture was warmed up to 15°C and stirred at 15°C for 12 hours. The mixture was poured into water (2 L) and stirred for 1 hour. The suspension was filtered and the cake was washed with water (1 L). The obtained solid was pulped with water (2 L), filtered and dried via vacuum to give a gray solid (80 g, 91%). 1H NMR (400 MHz, DMSO-d6) δ = 13.09 (br. s., 1H), 10.61 (br. s., 1H), 8.61 (d, J=5.6 Hz, 1H), 7.88-7.83 (m, 2H), 7.46-7.42 (m, 2H), 7.35 (m, 1H), 7.29-7.21 (m, 3H), 6.89 (br. s., 1H).

Workgroup F Info Chiral building block for ureas: This is being synthesized by your colleagues with my assistance . Building block for amides: This, I’ve purchased .

Always use the correct technique for your safety and best results! Technique updates! Always use the correct technique for your safety and best results!

Read all hazards on chemicals Downloaded on 9/6/16 from: http://scc.epfl.ch/files/content/sites/sbsst/files/shared/Images/Pictogramme-en.jpg and http://www.sigmaaldrich.com/content/dam/sigma-aldrich/customer-service/ghs/label-jpg.jpg

Microscale We will be running reactions typically on 100 mg or less! This might be on the new side for you It’s totally doable, but you need to always think about how you can adjust your technique for the best results! A few tips: 1) if you’re scaling down a lit procedure, think about your choice of glassware and, e.g., the need to use more solvent; 2) think about potential losses at every stage and minimize these (e.g. recover NMR samples in solvents that permit, use the proper size column, etc.); 3) don’t ever compromise safety (e.g. if you run your rxn in a vial, think about how to do it safely without creating a truly closed system)

Dispensing solids/liquids Please weigh all solids and dispense all liquids in the hood Downloaded on 9/6/16 from: https://www.mystaire.com/images/ductlessfumehoods/mylbe.png

Air sensitive reagent handling Please perform all of your reactions in dry glassware (you can use the drying oven) and under an Ar balloon atmosphere unless your reaction specifies otherwise Never use or heat a system that is closed! Downloaded on 10/31/16 from: http://chem.chem.rochester.edu/~nvd/img/pics/syringe1.jpg Downloaded on 10/31/16 from: http://2.bp.blogspot.com/-h3ar1ue5xDA/TZ-FGCtdMqI/AAAAAAAAAAQ/jWViE5PwHwA/s1600/IMG_0921.JPG

Hot plates and temp sensors In your hood unplug all hotplates, stirplates, variacs, and all other electrical devices when not in use If you use a combination temperature probe/hot plate, see Rob for special instructions – do NOT remove probe from oil bath while plate is on/plugged in Downloaded on 10/31/16 from: https://images-na.ssl-images-amazon.com/images/I/31CpjJ93o4L._AC_UL320_SR182,320_.jpg Downloaded on 10/31/16 from: https://images-na.ssl-images-amazon.com/images/I/41APGV6MPXL.jpg

Time Management Sounds like a pretty simple concept, but you really need to think about it in terms of how to maximize your time in the lab Remember, you are in pairs: how can you both be doing something productive at all times Can you come in as a pair the evening before on a Monday or Wednesday and set up a reaction safely that will be all ready to work up the next day when we meet for Superlab? Should you start B before F or vice versa? Should you work on them simultaneously? Is there such a thing as trying to do too much chemistry at one time?

Laboratory Notebooks Please use Rob’s template for an electronic notebook As you gather data for each successful reaction, make sure your procedures and spectral data are recorded in your electronic notebook in the form you see in Mowbray’s article (in J. Med. Chem. format) Print out a hard copy for each experiment when you are finished with it and put in your notebook as a back-up