반응 #218674

반응 방정식

pyridine

2-cyclopentyl-4,9-dihydro-3-thia-1,4,9-triazabenzo[f]azulene-10-thione

methyl triflate

(S)-2-(2-methoxyethyl)piperazine

→

(S)-10-[3-(2-methoxy-ethyl)-piperazin-1-yl]-2-cyclopentyl 4H-3-thia-1,4,9-triazabenzo[f]azulene

수율 52.5%

용매

dichloromethane

반응 조건

후처리

1. 1
   기타at 0° C
2. 2
   온도warm to room temperature overnight
3. 3
   기타Evaporate the mixture
4. 4
   온도heat
5. 5
   온도at reflux overnight
6. 6
   기타Evaporate the mixture
7. 7
   workup.ADDITIONdilute with methanol and apply to a 10 g SCX column
8. 8
   세척Wash with methanol
9. 9
   세척elute with a step gradient
10. 10
    기타to obtain the
11. 11
    기타Purify by flash chromatography
12. 12
    세척eluting with a step gradient

실험 절차

Combine 2-cyclopentyl-4,9-dihydro-3-thia-1,4,9-triazabenzo[f]azulene-10-thione (0.529 g, 1.75 mmol) and methyl triflate (0.24 mL, 2.11 mmol) in dichloromethane (3 mL) at 0° C. Stir the mixture at 0° C. for 15 minutes and warm to room temperature overnight. Evaporate the mixture, combine the residue with (S)-2-(2-methoxyethyl)piperazine (0.253 g, 1.75 mmol) and pyridine (3 mL) and heat at reflux overnight. Evaporate the mixture, then dilute with methanol and apply to a 10 g SCX column. Wash with methanol, then elute with a step gradient starting with dichloromethane going to 10% 2N ammonia-methanol in dichloromethane followed by 100% 2N ammonia-methanol to obtain the desired coupled product. Purify by flash chromatography, eluting with a step gradient starting with dichloromethane going to 6% 2N ammonia-methanol in dichloromethane, to give (S)-10-[3-(2-methoxy-ethyl)-piperazin-1-yl]-2-cyclopentyl 4H-3-thia-1,4,9-triazabenzo[f]azulene (0.378 g, 0.918 mmol, 52%) as a yellow amorphous solid: mass spectrum (APCI): m/z=412.2 (M+1).

출처