반응 #40281

반응 방정식

5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-ylamine

2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid

hydrochloric acid

pyridine

oxalyl chloride

→

2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-yl]-propionamide

수율 92.4%

용매

methylene chloride

methylene chloride

반응 조건

후처리

1. 1
   농축The reaction mixture was then concentrated in vacuo
2. 2
   workup.DISSOLUTIONThe residue was dissolved in benzene (25 mL)
3. 3
   기타the evaporation
4. 4
   workup.DISSOLUTIONThe resulting acid chloride was dissolved in methylene chloride (40 mL)
5. 5
   온도cooled to at 0° C.
6. 6
   workup.ADDITIONtreated with a solution
7. 7
   workup.STIRRINGThe mixture was stirred for 16 h
8. 8
   기타The layers were separated
9. 9
   추출the aqueous layer was extracted with methylene chloride (75 mL)
10. 10
    세척The organic layers were washed with a saturated aqueous sodium bicarbonate solution (100 mL)
11. 11
    건조The combined organic layers were dried over sodium sulfate
12. 12
    여과filtered
13. 13
    농축concentrated in vacuo

실험 절차

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 6.29 g, 19.01 mmol) and N,N-dimethylformamide (2 drops) in methylene chloride (70 mL) was stirred at 2° C. and then treated with oxalyl chloride (4.15 mL, 45.7 mmol). The mixture was stirred at 2° C. for 5 min and at 25° C. for 15 min. The reaction mixture was then concentrated in vacuo. The residue was dissolved in benzene (25 mL), and the evaporation was repeated. The resulting acid chloride was dissolved in methylene chloride (40 mL), cooled to at 0° C., and then treated with a solution composed of 5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-ylamine (3.65 g, 18.95 mmol), pyridine (4.6 mL, 56.9 mmol) and methylene chloride (40 mL). The mixture was stirred for 16 h without replenishing the cooling bath. The reaction mixture was then treated with a 1N aqueous hydrochloric acid solution (100 mL). The layers were separated, and the aqueous layer was extracted with methylene chloride (75 mL). The organic layers were washed with a saturated aqueous sodium bicarbonate solution (100 mL) and a saturated aqueous sodium chloride solution. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40 L, Silica, 1/1 ethyl acetate/hexanes) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-yl]-propionamide (8.9 g, 92%) as a white foam: (ES)+-HRMS m/e calcd for C24H30CiN3O5S (M+H)+ 508.1668, found 508.1671.

출처