N,N-Dimethylglycine → HCID 59272925, Verbindung

Temperatur

110 °C

A 250 mL one-neck round bottomed-flask with magnetic stirring and argon atmosphere was charged with cesium carbonate (30.3 g, 93.00 mmol), (1R,2S)-2-amino-1-(4H-benzo[d][1,3]dioxin-7-yl)propan-1-ol hydrochloride (I3) (7.37 g, 30.00 mmol), 2-(dimethylamino)acetic acid (1.547 g, 15.00 mmol), copper(I) iodide (1.428 g, 7.50 mmol) and butyronitrile (72 mL) and heated at 110° C. for 30 min. A solution of isobutyl 3-(5-iodo-1H-indazol-1-yl)benzoate (I1) (12.61 g, 30 mmol) in butyronitrile (12.00 mL) was generated by heating at 80° C. for 10 minutes. The solution was pumped to the above mixture within 3 minutes. The vessel was rinsed with further butyronitrile (6.00 mL) which also was added. The reaction mixture was sealed and stirred at 110° C. for 19 h. The reaction mixture was cooled and extracted between water and ethyl acetate (1 L). The organic phase was washed three times with water (3×500 mL), dried over magnesium sulfate and concentrated. The residue was purified by flash chromatography on silica using ethyl acetate:heptane 1:1 with 2% TEA followed by ethyl acetate:heptane 3:1 with 2% TEA and finally with ethyl acetate with 2% TEA. This gave the title compound (5.1 g, 34%).

1. temperatureby heating at 80° C. for 10 minutes
2. washThe vessel was rinsed with further butyronitrile (6.00 mL) which
3. additionalso was added
4. customThe reaction mixture was sealed
5. stirringstirred at 110° C. for 19 h
6. temperatureThe reaction mixture was cooled
7. extractionextracted between water and ethyl acetate (1 L)
8. washThe organic phase was washed three times with water (3×500 mL)
9. dry with materialdried over magnesium sulfate
10. concentrationconcentrated
11. customThe residue was purified by flash chromatography on silica

ORD-Eintrag

ord-b3eec1df55a04e48859b2e394df8e325

Quelldatensatz

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08916600B2