Vent for the aminohalogenation of methyl cinnamate (4a). To prove the
Vent for the aminohalogenation of methyl cinnamate (4a). To prove the synthetic value with the methodology, other popular principal or secondary amines, have been tested inside the reaction beneath optimized conditions (Table 2). The use of aliphatic amines, which include methylamine (Table 2, entry 2), dimethylamine (Table two, entry 3) and ammonia remedy (Table two, entry four), cause the formation of your aziridine as the sole item in 88 , 83 , 91 yield, respectively. Notably, a complicated mixture was obtained when 1,2-ethanediamine was applied ErbB2/HER2 Purity & Documentation within this reaction (Table two, entry 1).Outcomes and DiscussionAccording for the previous reports on the derivatization of aminohalogenation reactions, the vicinal haloamines commonly underwent elimination or aziridination reactions after they had been treated with organic bases (Scheme 2) [33-35]. Nevertheless, when benzylamine was added to haloamine 1a in acetonitrile, the reaction could also proceed smoothly giving a sole product.Scheme 1: An anomalous outcome with benzylamine as organic base.Scheme 2: Transformation of vicinal haloamines by the use of organic amines.Beilstein J. Org. Chem. 2014, ten, 1802807.Table 1: Optimization of typical reaction circumstances.aentry 1 two three 4 5 6 7 8 9aReactionamount (mL)b four four four 2 0.5 0.1 0.1 0.1 2solvent CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN CH2Cl2 CHClT ( ) rt 50 rt rt rt rt rt rt rt rttime (h) 0.5 0.five 1 1 1 1 3 6 1yield ( )c 83 75 91 93 63 28d 59d 60d 89conditions: 1a (0.5 mmol), solvent (three mL). bAmount of benzylamine. c Isolated yields. d2 mL triethylamine was added.Table 2: Examination of other organic bases.aentrybase (mL)T ( )time (min)item ( )b 3a 5a1 2 3aReaction1,2-ethanediamine (two) methylamine (2) dimethylamine (two) ammonia resolution (2)situations: 1a (0.5 mmol), acetonitrile (3 mL), base.rt rt rt rtbIsolated30 30 30yieldsplex mixture 88 83After getting the optimized circumstances, we then combined the aminohalogenation and the treatment of benyzlamine to develop a one-pot process with ,-unFGFR1 Compound saturated esters as starting components. On the initial reaction step the cinnamic ester underwent a copper(II) trifluoromethanesulfonate-catalyzed aminohalogenation reaction with TsNCl2 as nitrogen supply. Immediately after becoming quenched by saturated sodium sulfite, the resulting mixture was stirred with benzylamine. Several ,-unsaturated esters were studied to evaluate the yield and stereochemical outcome of these reactions (Table three). As shown in Table three, just about all of the tested substrates worked well beneath the optimized situations giving rise for the corresponding ,-diamino ester solutions, even though the aromatic ring was substituted by sturdy elec-tron-withdrawing groups (fluoro, Table 3, entries six, ten and 12; trifluoromethyl, entry 15) or an electron-donating group (methoxy, Table three, entry eight). In the case of ethyl ester, the reaction showed reduce reactivity (Table 3, entry two), and 70 chemical yield was obtained comparing to 79 yield from methyl ester (Table 3, entry 1). A cinnamic ester with double-substituted aromatic ring 4m was also tolerated in this reaction in addition to a moderate chemical yield (53 , Table three, entry 13). Notably, when the phenyl was replaced by 1-naphthyl 4n (Table three, entry 14), it was also nicely performing within this reaction giving rise to the target solution in 64 yield. For the substrates with ortho-substituents (Table 3, entries 13 and 16), the yields had been a little bit bit reduce than the yields on the meta- and para-Beilstein J. Org. Chem. 2014, ten, 1802807.Table three: One-pot reaction.