反应详情

A mixture of 4-[N-(2,3-difluoro-phenyl)-N′-amino-carbamimidoyl]-1-methanesulfonyl-1H-pyrrole-2-carboxylic acid methyl ester (200 mg, 0.54 mmol), CH(OEt)3 (4 mL), and HCOOH (0.8 mL) was stirred at room temperature for 2 hours and poured into 50 mL of aqueous NaHCO3 solution. The aqueous mixture was extracted with EtOAc and the combined organic layers were dried over Na2SO4, filtered, and evaporated. The crude material was used for the next step without further purification. This crude product was dissolved in MeOH (5 mL) then 6N NaOH aqeous solution was added (1 mL) and the mixture was heated at 50° C. for 3 hours. The solvent was evaporated and the residue was acidified with 6N HCl to pH 3. The white precipitate was collected by filtration and washed with water. The crude product (150 mg, 96%) was dried on the pump for the next reaction. 1H NMR (500 MHz, DMSO-d6) δ12.61 (s, br, 1H), 12.20 (s, 1H), 8.78 (s, 1H), 7.75 (m, 1H), 7.55 (m, 1H), 7.47 (m, 1H), 6.96 (s, 1H), 6.58 (s, 1H) ppm. MS (ES+): m/e=291.1 (M+H); LC/Method A/2.46 min.

1. extractionThe aqueous mixture was extracted with EtOAc
2. dry with materialthe combined organic layers were dried over Na2SO4
3. filtrationfiltered
4. customevaporated
5. customThe crude material was used for the next step without further purification
6. dissolutionThis crude product was dissolved in MeOH (5 mL)
7. addition6N NaOH aqeous solution was added (1 mL)
8. temperaturethe mixture was heated at 50° C. for 3 hours
9. customThe solvent was evaporated
10. filtrationThe white precipitate was collected by filtration
11. washwashed with water
12. dry with materialThe crude product (150 mg, 96%) was dried on the pump for the next reaction
13. customLC/Method A/2.46 min.