N-(tert-butoxycarbonyl)glycine → {1-[4-(5-Aminomethyl[1,2,4]oxadiazol-3-yl)phenyl)pyrrolidin-3-yl}dimethylamine

PyBOP (546.4 mg), HOAt (136.1 mg) and triethylamine (0.279 ml) were added to a mixture of 4-(3-dimethylaminopyrrolidin-1-yl)-N-hydroxybenzamidine (248.3 mg), tert-butoxycarbonylaminoacetic acid (175.2 mg) and DMF (2.8 ml) at 0° C. and the mixture was stirred at this temperature for 10 min. It was subsequently stirred at room temperature for 2 h and then ethyl acetate and water were added to the reaction solution. The organic phase then washed twice each with 10% strength citric acid solution, saturated sodium bicarbonate solution and water, dried over sodium sulfate and filtered, and the solvent removed in vacuo. The residue was then taken up in 6.2 ml of THF, and EDC (105 mg) and triethylamine (0.09 ml) were added, and the mixture was stirred at 50° C. for 16 h. Ethyl acetate and water were then added to the reaction solution. The organic phase then washed twice each with 10% strength citric acid solution, saturated sodium bicarbonate solution and water and dried over sodium sulfate, and the solvent removed in vacuo. The crude product was taken up in methylene chloride (9.6 ml), and trifluoroacetic acid (2.3 ml) was added. The reaction was stirred at room temperature for 5 h and then the solvent was removed in vacuo. The residue was purified by preparative HPLC. The product with the molecular weight of 287.37 (C15H21N50) was obtained in this way; MS (ESI): 288.05 (M+H+).

1. stirringIt was subsequently stirred at room temperature for 2 h
2. washThe organic phase then washed twice each with 10% strength citric acid solution, saturated sodium bicarbonate solution and water
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. customthe solvent removed in vacuo
6. additionEDC (105 mg) and triethylamine (0.09 ml) were added
7. stirringthe mixture was stirred at 50° C. for 16 h
8. additionEthyl acetate and water were then added to the reaction solution
9. washThe organic phase then washed twice each with 10% strength citric acid solution, saturated sodium bicarbonate solution and water
10. dry with materialdried over sodium sulfate
11. customthe solvent removed in vacuo
12. additiontrifluoroacetic acid (2.3 ml) was added
13. stirringThe reaction was stirred at room temperature for 5 h
14. customthe solvent was removed in vacuo
15. customThe residue was purified by preparative HPLC
16. customThe product with the molecular weight of 287.37 (C15H21N50) was obtained in this way

ORD record

ord-a09b77083da44b93bd17304bb00c6568

Source dataset

uspto-grants-2008_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07319108B2