반응 #1276188

반응 방정식

[2-(7-[2-methoxy-1-(methoxymethyl)ethoxy]-5-{[5-(methylsulfonyl)pyridin-2-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid

N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride

1-hydroxybenzotriazole

methylammonium chloride

→

title compound

수율 61.0%

2-[2-(7-[2-Methoxy-1-(methoxymethyl)ethoxy]-5-{[5-(methylsulfonyl)pyridin-2-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]-N-methylacetamide

수율 61.0%

용매

N,N-dimethylformamide

triethylamine

반응 조건

후처리

1. 1
   농축The mixture was concentrated under reduced pressure
2. 2
   workup.DISSOLUTIONThe residue was dissolved in water
3. 3
   추출the mixture was extracted with ethyl acetate-tetrahydrofuran
4. 4
   세척The organic layer was washed with saturated brine
5. 5
   건조dried over magnesium sulfate
6. 6
   여과filtered
7. 7
   농축concentrated
8. 8
   기타The residue was purified by basic silica gel column chromatography (methanol/ethyl acetate=0/100 to 5/95, volume ratio)
9. 9
   기타to give a pale yellow amorphous solid
10. 10
    기타The amorphous solid was crystallized from acetonitrile-diethyl ether
11. 11
    기타to give white crystals
12. 12
    기타The crystals were recrystallized from ethyl acetate-diethyl ether

실험 절차

A mixture of [2-(7-[2-methoxy-1-(methoxymethyl)ethoxy]-5-{[5-(methylsulfonyl)pyridin-2-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid (280 mg), N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (195 mg), 1-hydroxybenzotriazole (138 mg), methylammonium chloride (69 mg), triethylamine (0.14 mL) and N,N-dimethylformamide (15 mL) was stirred at room temperature for 2.5 h. The mixture was concentrated under reduced pressure. The residue was dissolved in water and the mixture was extracted with ethyl acetate-tetrahydrofuran. The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by basic silica gel column chromatography (methanol/ethyl acetate=0/100 to 5/95, volume ratio) to give a pale yellow amorphous solid. The amorphous solid was crystallized from acetonitrile-diethyl ether to give white crystals. The crystals were recrystallized from ethyl acetate-diethyl ether to give the title compound (174 mg, 61%) as colorless crystals. MS 563 (MH+). mp 123-125° C.

출처