An efficient and mild synthetic method was developed for tofacitinib citrate from 3-amino-4-methylpyridine and 4-chloro-7H-pyrrolo[2,3-d]pyrimidine. The related reactions were systematically optimized. Sodium hydride instead of potassium tert-butoxide employed in the methoxycarbonylation reaction of compound 9 made the reaction proceed effectively to present compound 8 in a better yield. The replacement of benzaldehyde with benzyl bromide simplified the protection process of amino group. Red-Al provided a cost-effective method for the reduction of amides. The introduction of tosyl group into compound 10 enhanced the nucleophilic substitution of 10 with compound 4 dramatically. Thus, under the optimized conditions, tofacitinib citrate was obtained in 13.3% yield (based on compound 9) with a purity of 99.9%, much better than the reported yield 8.6%. This cost-effective and environmental friendly process is more suitable for scale-up production.

Laquinimod, 5-chloro-1,2-dihydro-N-ethyl-4-hydroxy-1-methyl-2-oxo-N- phenyl-3-quinoline carboxamide, is an oral drug in clinical trials for the treatment of multiple sclerosis. An efficient synthetic method for laquinimod from 2-amino-6-chlorobenzoic acid via four steps was established. The overall yield of laquinimod is up to 82% as compared with 70% reported in literature. It has also been demonstrated that green reagent dimethyl carbonate is not suitable for the N-methylation of 5-chloroisatoic anhydride owing to the ring-cleavage reaction induced by the generated methanol. The ring-cleavage by-products were isolated and characterized by ¹H-NMR and ¹³C-NMR. In addition, in the study of laquinimod derivatives, we found that 5-chloro-1,2-dihydro-N-ethyl-4-hydroxy-1-methyl-2-oxo-N-phenyl-3-quinoline carboxamide (laquinimod) was obtained in much higher yield than 7-chloro-1,2-dihydro-N-ethyl-4-hydroxy-1-methyl-2-oxo-N-phenyl-3-quinoline carboxamide under the same reaction conditions, and it is possibly attributed to a neighboring group effect.

As a novel ultraviolet (UV) absorbent with excellent performance in UVA section (320 ~ 400 nm), 2-{2-hydroxy-4-[(octyloxycarbonyl)ethylideneoxy]phenyl}-4,6-Bis(4-biphenylyl)-1,3,5-triazine (CGL-479) was synthesized in a simple method with a total yield of 45.3% in four steps. Its outstanding UV absorption capability (λ_max = 326 nm, ε_max = 4.15 × 10⁴ L•mol⁻¹•cm⁻¹), high thermostability [T₅ (the temperature of losing 5% in weight) = 385 °C], and compatibility with polymer materials make it a potential substitute of the traditional UV absorbents.

An efficient synthetic method for the pemetrexed disodium has been developed using methyl 4-iodobenzoate and 3-buten-1-ol as starting materials via six steps. The developed process avoided some tedious workup procedures and unfriendly reagents compared with the reported synthetic routes. In addition, two impurities generated in the process were isolated and characterized by ¹H NMR, ¹³C NMR, and HRMS. The mechanisms of the two impurities were also discussed, and the impurities could be easily removed by suitable workup procedures. The overall yield of pemetrexed disodium was increased from 12.8% (literature) to 34.9%. Therefore, this cost-effective, environmental friendly, and high-yielding process is more suitable for scale-up production of pemetrexed disodium.

A series of pyridine Rho kinase inhibitors were designed and synthesized utilizing the ligand-binding pocket model with Y-26732 as the lead compound. These compounds were evaluated on cell lines for their biological activities.

The asymmetric domino oxa-Michael–Henry reaction of salicylaldehyde derivatives with trans-β-nitro olefins catalyzed by a readily available trans-4-hydroxy-L-prolinamide with 4-nitrophenol as an effective cocatalyst is presented. The corresponding 3-nitro-2H-chromenes were obtained in moderate to excellent yields (up to 99 %) and with up to 90 % ee under mild conditions. In addition, a preliminary study shows that this organocatalytic system is able to promote the domino aza-Michael–Henry reaction of 2-formylpyrrole derivatives with trans-β-nitro olefins to give chiral 2-nitro-3H-pyrrolizines.

Cyclohexanone was chosen as a model substrate to evaluate certain catalysts for the hydrodeoxygenation of aliphatic ketones in a fixed-bed reactor. The experimental results indicated that alkali-treated Ni/HZSM-5 exhibited excellent performance for this reaction. Two aspects of the catalyst are enhanced by alkaline treatment; the amount of strong acid sites on the catalyst is sharply reduced, and also a large number of mesopores are generated in the catalyst. The decrease of strong acid sites suppresses the formation of low-boiling products and aldol-condensation side products, while the mesopores improved hydrogenation and dehydration performances of the catalyst. These two aspects also promoted the catalyst’s excellent time-on-stream performance. Additionally, generality of the catalyst is proved; most of the selected carbonyl compounds can be hydrodeoxygenated to the corresponding alkanes with selectivities of more than 97.0 %.