Triethylamine → 6-Bromo-2-(diethoxymethyl)-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridine

温度

60 °C

To DMF (3.4 mL) containing triethylamine (0.64 mL, 0.46 g 4.5 mmole) was added propargylaldehyde diethyl acetal (183 uL, 163 mg, 1.27 mmole) and N-(2-bromo-5-iodopyridin-4-yl)methanesulfonamide, (Preparation 8, 400 mg 1.06 mmole) followed by copper(I) iodide (7.1 mg, 0.037 mmole). The reaction was placed under nitrogen. Bis(triphenylphosphine)palladium dichloride (26.1 mg, 0.037 mmole) was added and the reaction was flushed again with nitrogen, then heated at 60° C. for 2 hours. The reaction was cooled and added to water (35 mL) containing a sodium bicarbonate solution (3 mL). The reaction was extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with water containing sodium bicarbonate solution (3×10 mL), brine and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 100% dichloromethane to 5% ethyl acetate in dichloromethane to 10% ethyl acetate in dichloromethane to give the title compound (207 mg, 51%). 1H-NMR (CDCl3, 500 MHz): δ 1.32 (t, J=6.94 Hz, 6H), 3.38 (s, 3H), 3.75 (m, 2H), 3.84 (m, 2H), 5.86 (d, J=0.95 Hz, 1H), 6.94 (t, J=0.95 Hz, 1H), 8.14 (t, J=0.95 Hz, 1H), 8.67 (d, J=0.95 Hz, 1H).

1. additionwas added
2. customthe reaction was flushed again with nitrogen
3. temperatureThe reaction was cooled
4. additionadded to water (35 mL)
5. additioncontaining a sodium bicarbonate solution (3 mL)
6. extractionThe reaction was extracted with ethyl acetate (3×20 mL)
7. washThe combined organic layers were washed with water
8. additioncontaining sodium bicarbonate solution (3×10 mL), brine
9. concentrationconcentrated in vacuo
10. customThe residue was purified
11. washeluting with 100% dichloromethane to 5% ethyl acetate in dichloromethane to 10% ethyl acetate in dichloromethane

ORDレコード

ord-086a562d38164ae5816bdbf229e082e6

出典データセット

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09371319B2