Dimethylformamide → Methyl 1-amino-5-carbamoyl-1H-pyrrole-3-carboxylate

Temperature

0 °C

The compound pyrrole-1,3-dicarboxylate 1 (5 g, 25.4 mmol, prepared according to Kamijo, S., Kanazawa, C., and Yamamoto Y. J. AM. CHEM. SOC. 2005, 127, 9260-9266, wherein the starting materials methyl propiolate and ethyl isocyanoacetate were purchased from Darui chemical Co., Ltd) was dissolved in 25 mL of anhydrous N,N-dimethylformamide, and cooled in an ice bath to 0° C. Sodium hydride (60%, dispensed in mineral oil, 1.22 g, 30.5 mmol) was added in batches. The mixture was stirred for 1 hour at room temperature. Then 300 mL of chloramine solution in diethyl ether prepared in advance was added in one portion and stirred overnight at room temperature under nitrogen atmosphere. The reaction mixture was quenched with saturated sodium thiosulfate solution and diluted with water. The diethyl ether layer was separated and the aqueous layer was extracted once with ethyl acetate. The organic layers were combined and washed with water for three times, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 6.2 g of crude product which is directly subjected to ammonolysis without purification. To each 3 g of crude product was added 80 mL of saturated solution of ammonia in methanol and the reaction was carried out at 80° C. in a sealed tube for 2 days. The reaction mixture was concentrated to precipitate solid, then allowed to settle for about 1 hour, and filtered to obtain 3 g product as white solid. The yield of two steps was 64.6%. m.p. 222-224° C.

1. additionwas added in one portion
2. stirringstirred overnight at room temperature under nitrogen atmosphere
3. customThe reaction mixture was quenched with saturated sodium thiosulfate solution
4. additiondiluted with water
5. customThe diethyl ether layer was separated
6. extractionthe aqueous layer was extracted once with ethyl acetate
7. washwashed with water for three times
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationconcentrated under reduced pressure
10. customto give 6.2 g of crude product which
11. customis directly subjected to ammonolysis without purification
12. additionTo each 3 g of crude product was added 80 mL of saturated solution of ammonia in methanol
13. waitthe reaction was carried out at 80° C. in a sealed tube for 2 days
14. concentrationThe reaction mixture was concentrated
15. customto precipitate solid
16. waitto settle for about 1 hour
17. filtrationfiltered

ORD record

ord-a25b499cdee64f3cb63da1a787375ae9

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09447101B2