Propyne → HCID 58365126, Verbindung

Temperatur

-40 °C

Propyne (35 g, 0.87 mol) was condensed into a pre-weighed flask cooled to ca. −40° C. containing THF (100 mL). The solution was added via cannula to a cooled (0-5° C.), degassed mixture of 5-chloro-3-iodo-pyridin-2-ylamine (81.4 g, 0.32 mol), bis(triphenylphosphine)dichloropalladium(0) (4.49 g, 6.4 mmol), copper (I) iodide (1.46 g, 7.67 mmol) and triethylamine (97.3 g, 134 mL, 0.98 mol) in THF (900 mL). The mixture was stirred at 0-5° C. for 30 minutes then for a further 30 minutes at ambient temperature. The solid was removed by filtration and the cake washed with THF. The filtrate was diluted with ethyl acetate and extracted with 2M hydrochloric acid (×3). The combined acid extract was washed with diethyl ether and then made basic by careful addition of potassium carbonate then extracted with diethyl ether (×3). The combined organic layer was dried (Na2SO4), filtered and evaporated to afford the title compound as a brown solid (53.8 g, quantitative yield). LCMS (Method B): RT=3.55 min, M+H+=167/169. 1H NMR (300 MHz, CDCl3): 7.92 (d, J=2.5 Hz, 1H), 7.42 (d, J=2.5 Hz, 1H), 5.00 (s, 2H), 2.10 (s, 3H).

1. customcondensed into a pre-weighed flask
2. additionThe solution was added via cannula to
3. temperaturea cooled (0-5° C.)
4. customdegassed
5. waitfor a further 30 minutes at ambient temperature
6. customThe solid was removed by filtration
7. washthe cake washed with THF
8. additionThe filtrate was diluted with ethyl acetate
9. extractionextracted with 2M hydrochloric acid (×3)
10. extractionThe combined acid extract
11. washwas washed with diethyl ether
12. additionmade basic by careful addition of potassium carbonate
13. extractionthen extracted with diethyl ether (×3)
14. dry with materialThe combined organic layer was dried (Na2SO4)
15. filtrationfiltered
16. customevaporated

ORD-Eintrag

ord-d5f624be23b7443fa48e60985222f87e

Quelldatensatz

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09440976B2