For the AT1 Receptor Storage & Stability synthesis of ,-diamino ester.aentry 1 2 3 four five six 7 eight 9 10 11 12 13 14 15aReactionAr C6H5 C
For the synthesis of ,-diamino ester.aentry 1 two 3 4 five six 7 8 9 10 11 12 13 14 15aReactionAr C6H5 C6H5 4-CH3-C6H4 4-Br-C6H4 4-Cl-C6H4 4-F-C6H4 4-CF3O-C6H4 3-CH3O-C6H4 3-Cl-C6H4 3-F-C6H4 2-Cl-C6H4 2-F-C6H4 2,6-di-Cl-C6H3 1-naphthyl 3-CF3-C6H4 2-Br-C6HR Me Et Me Me Me Me Me Me Me Me Me Me Me Me Me Meproduct 5a 5b 5c 5d 5e 5f 5g 5h 5i 5j 5k 5l 5m 5n 5o 5pyield ( )b 79 70 67 72 68 78 80 70 67 75 63 83 53 64 74anti:syn c 99:1 99:1 99:1 99:1 99:1 99:1 99:1 99:1 99:1 99:1 99:1 99:1 99:1 99:1 99:1 99:conditions: 1) 10 mol Cu(OTf)2, 0.5 mmol cinnamic ester four, 1.0 mmol TsNCl2, 250 mg 4 molecular sieves in three.0 mL acetonitrile at area temperature for 24 h; two) Quenched by 3 mL saturated Na2SO3 for 30 min; 3) IL-23 Purity & Documentation benzylamine 2.0 mL at room temperature for 1 h. bIsolated yield. cDetermined by 1H NMR.substituted substrates, which indicates that the steric hindrance impacts the formation of your solution. Moreover, excellent stereoselectivity was obtained for all of the examined cinnamic ester substrates, and only the anti-isomers had been observed. To determine the structure of product 5, single crystals had been prepared. Fortunately, the crystals of product 5o had a fantastic crystallinity and were appropriate for single crystal X-ray evaluation (Figure 1). Crystallographic analysis has revealed that the antivicinal diamino ester was obtained. Because of this, the stereochemistry from the other solutions was assigned (anti-isomer) based on the similarity of their properties. Lastly, some reactions were in addition conducted to obtain insight into the reaction mechanism. Initially, we prepared the aziridine six in line with the reported strategy with cinnamic ethyl ester as beginning material [33]. Then, we used the aziridine 6 as beginning material to react with benzylamine below equivalent reaction conditions of the third step of this one-pot reaction (Scheme three). To our delight, aziridine six was converted into the corresponding diamino acid ester 5b with 73 chemical yield. Hence, aziridine probably could possibly be the intermediate within this reaction.Figure 1: ORTEP diagram of compound 5o.According to the above final results, a proposed reaction mechanism for this one-pot reaction is illustrated in Scheme four, which consists of the sequence of aminochlorination, aziridination and followed by the S N two nucleophilic ring-opening. The first step will be the Cu-catalyzed aminochlorination reaction of methyl cinnamate 1a resulting in anti-chloroamine intermediate A. The secondBeilstein J. Org. Chem. 2014, 10, 1802807.affording the target solutions in good-to-excellent chemical yields. Furthermore, this reaction gives virtually full stereochemical outcomes, and only the anti-isomer is identified for all of the situations, which offers an easy access to ,-diamino acid derivatives.Scheme three: Ring-opening of aziridine 6.ExperimentalGeneral procedure for the one-pot synthesis of ,-diamino esters: Into a dry vial was added cinnamic ester four (0.50 mmol) and freshly distilled acetonitrile (3.0 mL). The reaction vial was loaded with freshly activated 4 molecular sieves (250 mg), TsNCl2 (1.0 mmol) and Cu(OTf)two (ten mol ). The answer within the capped vial was stirred at room temperature for 24 h without argon protection. The reaction was lastly quenched by dropwise addition of saturated aqueous Na2SO3 option (3.0 mL). Soon after quench for 30 min, benzylamine (two.0 mL) was added towards the mixture exposed to air. Another 1 hour was necessary until conversion was full. Then the phases had been separated, plus the aqueous phase was extracted with ethyl a.