反应详情

温度

0 °C

Acetic acid (0.053 mL) was added to a mixture of 7-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2,2-dimethylheptanal (example 102, step d) (0.33 g) and (R)-7-(2-amino-1-hydroxyethyl)-4-hydroxybenzo[d]thiazol-2(3H)-one hydrochloride (WO2007027134, example 1, step d) (0.25 g) with 3 Å molecular sieves in anhydrous methanol (10 mL). The mixture was stirred for 5 min then cooled to 0° C. Sodium triacetoxyborohydride (0.13 g) was added and the resulting mixture stirred at RT for 16.5 h. The solution was filtered then concentrated in vacuo. The residue was dissolved in a mixture of acetonitrile and water and purified by preparative HPLC (Phenomenex Gemini®, Gradient: 10-40% acetonitrile in 0.1% aqueous formic acid). The fractions containing product were combined and freeze-dried to give the titled compound as a white solid. Yield 0.1 g.

1. stirringthe resulting mixture stirred at RT for 16.5 h
2. filtrationThe solution was filtered
3. concentrationthen concentrated in vacuo
4. dissolutionThe residue was dissolved in a mixture of acetonitrile and water
5. custompurified by preparative HPLC (Phenomenex Gemini®, Gradient: 10-40% acetonitrile in 0.1% aqueous formic acid)
6. additionThe fractions containing product
7. customfreeze-dried