5-Formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid - Reaction / Application on synthetic works

5-Formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid is an important organic intermediate to synthetize substituted pyrrole products.

The following example is about its application on the preparation of 3-(pyrrol-2-yl)methylene)-2-pyrrolones [1]

(NH4)2SO4 (0.09 g, 0.67 mmol) was added into a stirred mixture of 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (1.0 g, 6.61 mmol) in HMDS (20 mL, 20 P) at room temperature. The reaction mixture was then heated to reflux and maintained at that temperature for no less than 5 hours. Monitor the reaction by GC. 

After the reaction is completed, TMSOTf (0.29 g, 1.32 mmol) was added. Then the mixture was stirred, once the reaction was complete (as indicated by HPLC analysis) it was quenched with water (6 mL, 6 P.) and MeCN (30 mL). The mixture was filtrated and the filtrate cake was washed with MeCN (20 mL) and EtOH (5 mL), then it was dried under vacuum at 40° C. overnight to give the goal product (1.92 g, 97 percent yield) as a yellow to brown powder with about 82.1 percent HPLC purity.

The following example is about its application on the synthesis of 7-aza-indolin-2-ketone [2]

2,4-dimethyl-5-aldehyde-1H- pyrrole-3-carboxylic acid( 167 mg, 1 mmol),1- (3-Dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride(230 mg, 1.2 mmol),1-hydroxybenzotriazole(162 mg, 1.2 mmol) and N, N-dimethylformamide(15 mL) was stirred at 0-4 ° C for 20 min, N, N-dimethylethylenediamine (0.26 mL, 2 mmol) was added. The reaction temperature was 3 0min after stirring at room temperature for 12h. Add distilled water and dilute it with saturated sodium carbonate solution to adjust pH = 9, extract 15mL×3 times with dichloromethane containing 10 percent methanol, wash once with water, once with saturated saline, and dry over anhydrous sodium sulfate. Suction filtration, the filtrate was concentrated under reduced pressure to give a red oily liquid (yield 59 percent).

The following example is about its application on the synthesis of a ratiometric fluorescent probe [3]

A solution of 5 formyl 2,4 dimethyl 1H pyrrole 3 carboxylic acid (230mg, 1mmol) dissolved in DMF (10 mL) was stirred at room temperature while N (3 dimethylaminopropyl) N ethylcarbodiimide hydrochloride (192mg, 1mmol), hydroxybenzotriazole hydrate (153mg, 1mmol), triethylamine (101mg, 1mmol), and N (2 aminoethyl)morpholine (130mg, 1mmol) were added. The reaction mixture was stirred at room temperature for 12h. The 5 formyl 2,4 dimethyl 1H pyrrole 3 carboxylic acid (2 morpholin 4 yl ethyl) amide (1a) was filtered, washed with DMF and then dried in air. Yield 82 percent. 

References

1.Scinopharm Taiwan, Ltd. Henscheke JP, Chen YF. Processes for the preparation of 3-(pyrrol-2-yl)methylene)-2-pyrrolones using 2-silyloxy-pyrroles. WO2013/190512[P], 2013, A1, Paragraph 0088.
2.Zhejiang Sitaili Pharmaceutical Co., Ltd. Chinese Academy of Medical Sciences Pharmaceutical Bio-technology Institute. Liu M, Guo H, Wang M, Xia G, Li L, Wang C, Shen W, Chen S. 7-aza-indolin-2-ketone compound and its preparation method (by machine translation). CN104876928[P], 2016, B, Paragraph 0049-0050
3.Wu WN, Wu H, Zhong RB, Wang Y, Xu ZH, Zhao XL, Xu ZQ, Fan YC. Ratiometric fluorescent probe based on pyrrole-modified rhodamine 6G hydrazone for the imaging of Cu2+ in lysosomes[J]. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2019,212:121 – 127.

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