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4. Thayer, A. M. Chem. Eng. News 2014, 92, 13–21.
presented in Table 1; reactants 1 and 2x were mixed together in
reactor 1 at 20 °C at a flow rate of 125 µL/min. The reaction
mixture was then pumped to reactor 2, which was kept at 40 °C.
The third reactant (2y) was then added at a flow rate of
250 µL/min. The residence times were 1 min and 2 min, respec-
tively. Once the mixture passed both reactors, the final com-
pound concentration was 10 mM and could be used as a stock
solution for initial screening. For the larger scale experiments,
the work-up procedure was similar to a batch reaction. The sol-
vent was removed in vacuo and the remaining oil was dis-
solved in diethyl ether. It was subsequently washed with a
hydrogen chloride solution of 1 M and with a saturated sodium
bicarbonate solution. The organic phase was dried with MgSO4,
the solvent was evaporated in vacuo, and the residue was puri-
fied by either preparative thin-layer chromatography or by
recrystallization.
5. Poechlauer, P.; Manley, J.; Broxterman, R.; Gregertsen, B.;
Ridemark, M. Org. Process Res. Dev. 2012, 16, 1586–1590.
6. Baxendale, I. R.; Braatz, R. D.; Hodnett, B. K.; Jensen, K. F.;
Johnson, M. D.; Sharratt, P.; Sherlock, J.-P.; Florence, A. J.
7. Rodrigues, T.; Schneider, P.; Schneider, G. Angew. Chem. 2014, 126,
8. Malet-Sanz, L.; Susanne, F. J. Med. Chem. 2012, 55, 4062–4098.
9. Poechlauer, P.; Colberg, J.; Fisher, E.; Jansen, M.; Johnson, M. D.;
Koenig, S. G.; Lawler, M.; Laporte, T.; Manley, J.; Martin, B.;
O’Kearney-McMullan, A. Org. Process Res. Dev. 2013, 17,
10.Baumann, M.; Baxendale, I. R. Beilstein J. Org. Chem. 2015, 11,
11.Porta, R.; Benaglia, M.; Puglisi, A. Org. Process Res. Dev. 2016, 20,
12.Taylor, D. M.; Balabadra, U.; Xiang, Z.; Woodman, B.; Meade, S.;
Amore, A.; Maxwell, M. M.; Reeves, S.; Bates, G. P.; Luthi-Carter, R.;
Lowden, P. A. S.; Kazantsev, A. G. ACS Chem. Biol. 2011, 6,
b) Continuous process with secondary amines as F1: Triethyl-
amine and a secundary amine (F1) were dissolved in aceto-
nitrile (c = 5 mM), m-chlorosulfonylbenzoyl chloride (F2) was
dissolved in acetonitrile in a second volumetric flask
(c = 5 mM). A third solution was prepared with dimethylamino-
pyridine (DMAP) and the second reactant (F3) (c = 2.5 mM).
The flow process is presented in Table 3; reactants 1 and 2x
were mixed together in reactor 1 at 0 °C at a flow rate of
500 µL/min. The reaction mixture was then pumped to reactor
2, which was kept at 75 °C. The third reactant (2y) was then
added at a flow rate of 1000 µL/min. The residence times were
0.25 min and 0.5 min, respectively. Once the mixture passed
both reactors, the final compound concentration was 1.25 mM
and could be used as a stock solution for screening.
13.Chopra, V.; Quinti, L.; Kim, J.; Vollor, L.; Narayanan, K. L.; Edgerly, C.;
Cipicchio, P. M.; Lauver, M. A.; Choi, S. H.; Silverman, R. B.;
Ferrante, R. J.; Hersch, S.; Kazantsev, A. G. Cell Rep. 2012, 2,
14.Zhang, X.; Smith, D. L.; Meriin, A. B.; Engemann, S.; Russel, D. E.;
Roark, M.; Washington, S. L.; Maxwell, M. M.; Marsh, J. L.;
Thompson, L. M.; Wanker, E. E.; Young, A. B.; Housman, D. E.;
Bates, G. P.; Sherman, M. Y.; Kazantsev, A. G.
Proc. Natl. Acad. Sci. U. S. A. 2005, 102, 892–897.
15.Khanfar, M. A.; Quinti, L.; Wang, H.; Choi, S. H.; Kazantsev, A. G.;
Silverman, R. B. Eur. J. Med. Chem. 2014, 76, 414–426.
16.Dolle, R.; Worm, K.; Zhou, Q. Sulfamoyl benzamide derivatives and
methods of their use. U.S. Patent US20060079557 A1, April 13, 2006.
17.Choi, S. H.; Quinti, L.; Kazantsev, A. G.; Silverman, R. B.
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Supporting Information
Supporting Information File 1
Experimental part.
18.Yang, Y.-L.; Rajagopal, B.; Liang, C.-F.; Chen, C.-C.; Lai, H.-P.;
Chou, C.-H.; Lee, Y.-P.; Yang, Y.-L.; Zeng, J.-W.; Ou, C.-L.; Lin, P.-C.
19.Seghers, S.; Van Waes, F. E. A.; Cukalovic, A.; Monbaliu, J.-C. M.;
De Visscher, J.; Thybaut, J. W.; Heugebaert, T. S. A.; Stevens, C. V.
20.Baxendale, I. R.; Griffiths-Jones, C. M.; Ley, S. V.; Tranmer, G. K.
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