Ethanol → HCID 178522939, Verbindung

Formaldehyde (2.6 mL) is added to morpholine (2.7 mL) at 0° C. Ethanol (10 mL) is then added followed by addition of N-(4-chlorobenzyl)-4-hydroxythieno[2,3-b]pyridine-5-carboxamide (1.00 g) from Example No. 1. Acetic acid (2 mL) is added, and the reaction mixture is allowed to warm to rt and then refluxed for 18 h. Additional morpholine (2.7 mL) and formaldehyde (2.6 mL) are added and the reaction is refluxed for an additional 24 h. The reaction mixture is allowed to cool to room temperature and is then concentrated in vacuo. The residue is treated with 25% NaOH (20 mL). The aqueous layer is extracted with ethyl acetate (50 mL) then CHCl3 (60 mL). Methanol (30 mL) is added to the aqueous layer and it is extracted with CHCl3 (2×60 mL). This procedure is repeated 3 times. The combined organic layers are dried with MgSO4, filtered, and concentrated in vacuo. The resulting brown solid is purified by column chromatography (CH2Cl2/methanol, 98/2; 96/4) to yield a tan solid which is recrystallized from ethyl acetate/Et2O to yield 0.718 g (55%) of the title compound as an off-white solid.

1. temperaturerefluxed for 18 h
2. temperaturethe reaction is refluxed for an additional 24 h
3. temperatureto cool to room temperature
4. concentrationis then concentrated in vacuo
5. additionThe residue is treated with 25% NaOH (20 mL)
6. extractionThe aqueous layer is extracted with ethyl acetate (50 mL)
7. additionMethanol (30 mL) is added to the aqueous layer and it
8. extractionis extracted with CHCl3 (2×60 mL)
9. dry with materialThe combined organic layers are dried with MgSO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe resulting brown solid is purified by column chromatography (CH2Cl2/methanol, 98/2; 96/4)
13. customto yield a tan solid which
14. customis recrystallized from ethyl acetate/Et2O

ORD-Eintrag

ord-640d58eb2e1346caaf0381823fc3daef

Quelldatensatz

uspto-grants-2001_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06239142B1