Reaction #77681

Reaction equation

2-[4-(2-methyl-thiazol-4-yl)-phenoxy]-ethylamine

toluene-4-sulfonic acid 2-(6-acetylamino-pyridin-3-yl)-2-(tert-butyl-dimethyl-silanyloxy)-ethyl ester

diisopropyl ethyl amine

→

desired product

Yield 45.0%

(R)-N-[5-(1-(tert-Butyl-dimethyl-silanyloxy)-2-{2-[4-(2-methyl-thiazol-4-yl)-phenoxy]ethylamino}-ethyl)-pyridin-2-yl]-acetamide

Yield 45.0%

Solvents

dimethylsulfoxide

Conditions

Workup

1. 1
   Otherwas then partitioned between diethyl ether and water
2. 2
   ExtractionThe aqueous phase was extracted with diethyl ether four times
3. 3
   Washthe combined organic extracts were then washed with brine
4. 4
   Dryingdried over magnesium sulfate
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated in vacuo
7. 7
   OtherThe resulting white solid was purified by column chromatography (methylene chloride to 10% methanol/methylene chloride)

Procedure

In a round-bottomed flask, 2-[4-(2-methyl-thiazol-4-yl)-phenoxy]-ethylamine (175 mg, 0.747 mmol) and toluene-4-sulfonic acid 2-(6-acetylamino-pyridin-3-yl)-2-(tert-butyl-dimethyl-silanyloxy)-ethyl ester (231 mg, 0.498 mmol) were dissolved in dimethylsulfoxide (0.50 mL), and diisopropyl ethyl amine (0.105 mL, 0.600 mmol) was added in one portion. The resulting mixture was heated to about 80° C. for about sixteen hours, and was then partitioned between diethyl ether and water. The aqueous phase was extracted with diethyl ether four times, and the combined organic extracts were then washed with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting white solid was purified by column chromatography (methylene chloride to 10% methanol/methylene chloride) to afford 117 mg (45%) of the desired product. LRMS ([M+1]+): 527.1.

Source