2-Chloro-4-formylthiazole

2-Chlorothiazole (50 mmol) was dissolved in 100 mL of tetrahydrofuran to prepare solution A; solution B was a solution of lithium diisopropylamidein tetrahydrofuran-cyclohexane, and the concentration of lithium diisopropylamide was 2.0 mol/L. Solution B was purchased from Saan Chemical Technology(Shanghai) Co., Ltd.The solution A was placed in a dry ice acetone bath to cool to -78 C, and the solution B was slowly added dropwise (solution B was added in an amount of26 mL). After the addition was completed, the reaction was kept at -78 C for 0.5 hour, and then added dropwise. Piperidine-1-carbaldehyde (70 mmol), after completion of thedropwise addition, the reaction was continued at -78 C for 10 minutes, the dry ice acetone bath was removed, and the reaction was allowed to proceed to room temperature for 2 hours. After the reaction was completed, thereaction solution was poured into 50 mL of dilute hydrochloric acid. (2 mol / L) in the reaction was quenched, aqueous ammonia was added to neutral pH, dichloromethane was added into theline, and the extract phase was washed with saturated brine, dried over sodium sulfate, and the solvent removed to give a yellow solid 6.27 g The yield is 85%.2-Chlorothiazole (50 mmol) was dissolved in 100 mL of tetrahydrofuran to prepare solution A; solution B was a solution of lithium diisopropylamidein tetrahydrofuran-cyclohexane, and the concentration of lithium diisopropylamide was 2.0 mol/L. Solution B was purchased from Saan Chemical Technology(Shanghai) Co., Ltd.The solution A was placed in a dry ice acetone bath to cool to -78 C, and the solution B was slowly added dropwise (solution B was added in an amount of26 mL). After the addition was completed, the reaction was incubated at -78 C for 0.5 hour, and then added dropwise. N, N- dimethylformamide (70mmol), after the addition was complete, the reaction was continued at -78 10 minutes dry ice-acetone bath was removed and the reaction warmed to room temperature for 2 hours inverseshould be ended, the reaction solution was poured The reaction was quenched in 50 mL of dilute hydrochloric acid (2 mol/L), then added with aqueous ammonia to adjust the pH to neutral.Methylene chloride wasaddedfor extraction. The extracted phase was washed successively with saturated brine, dried over sodium sulfate, and then removed. The solvent gave 7.08 g of a yellow solid to give the product of 2-chloro-1, 3-thiazole-5-carbaldehyde in a yield of 96%.2. To a solution of 2 (2.66 g, 18.0 mmol) in dry THF (50 mL) was added n-BuLi (2.5 M in hexane, 7.2 mL, 18.0 mmol) dropwise at -78 C under N2. After 1 h, a solution of 2-chloro-4- thiazolecarboxaldehyde (Sigma-Aldrich, 4.00 g, 18.02 mmol) in THF (10 mL) was added dropwise. The resulting mixture was warmed to room temperature. The reaction was quenched with saturated NH4C1 and extracted with EtOAc. The combined organic extracts were concentrated to give a crude oil which was purified by silica gel chromatography to afford 3 (420 mg, 8% yield) as a yellow oil.General procedure: A solution of 2, 3-diamino-1, 4-naphthoquinone (1.0 mmol), appropriate aromatic aldehyde (1.0 mmol) with sodium pyrosulfitein DMF was stirred at 120 C overnight. On completion of the reactionmonitored by TLC, the solvent was evaporated and the residuewas purified by silica gel chromatography by DCM/MeOHsystem to afford the final product. If necessary, the crude productcould be recrystallized in methanol or DMSO to afford pure sample.4.1.5.1. 2-(2-Chlorophenyl)-1H-naphtho[2, 3-d]imidazole-4, 9-dione(T1). Pale yellow solid; yield 80%;