Trisodium 3,3',3''-phosphinetriyltris(benzene-1-sulphonate) → Isobutyl 2-(4-(1,3,4-oxadiazol-2-yl)phenyl)pyridin-3-ylsulfonyl(3-methoxy-5-methylpyrazin-2-yl)carbamate

온도

105 °C

Palladium acetate (0.4144 g) and 3,3′,3″-phosphinidyne tris(benzenesulphonic acid) trisodium salt 30% w/w aq sol (3.26 g) were dissolved in water (35 ml) over 6 minutes in an ultrasonic bath. The yellow solution was added to a stirred slurry of [4-(1,3,4-oxadiazol-2-yl)phenyl]boronic acid (10 g) and isobutyl [(2-chloropyridin-3-yl)sulfonyl](3-methoxy-5-methylpyrazin-2-yl)carbamate (16.86 g) in xylene (100 ml), industrial methylated spirit (50 ml) and triethylamine (17 ml). The catalyst dissolution flask was then washed in with water (5 ml) and the reaction mixture heated to reflux (80° C.) on an oil bath (105° C.) and stirred at reflux for 24.5 hours. The reaction mixture was cooled to 30° C. and filtered through a Whatman GF/B glass filter paper and the lower aqueous phase separated off. The reaction flask and filter cake was washed with xylene (20 ml). The xylene wash was used to re-extract the aqueous phase. The combined organic phases were stirred and heated to reflux (85° C.) in a clean 500 ml 4-necked flask equipped with overhead stirrer, water condenser, and nitrogen atmosphere. Essochem solvent 30 (hydrocarbons Bp 100-130° C.) (100 ml) was added dropwise over 6 min and the mixture was allowed to self cool to ambient temperature and then further cooled to −5° C. and held for 1 hour. The product was filtered off and washed with Essochem solvent 30 (50 ml). The cake was dried on the filter for 3 hours to give 15.20 g@100% strength, yield 76.8%. 270 MHz 1H-NMR Spectrum: 0.70 (d, 6H), 1.72 (m, 1H), 2.51 (s, 3H), 3.84 (d, 2H), 4.00 (s, 3H), 7.59 (m, 1H); 7.80 (d, 2H), 7.90 (s, 1H), 8.17 (d, 2H), 8.50 (s, 1H), 8.90 (m, 1H) and 9.00 (d, 1H). Mass Spectrum MH+=525.2 (C24H25N6O6S=525.16).

1. dissolutionThe catalyst dissolution flask
2. washwas then washed in with water (5 ml)
3. temperaturethe reaction mixture heated
4. temperatureat reflux for 24.5 hours
5. temperatureThe reaction mixture was cooled to 30° C.
6. filtrationfiltered through a Whatman GF/B glass
7. filtrationfilter paper
8. customthe lower aqueous phase separated off
9. filtrationThe reaction flask and filter cake
10. washwas washed with xylene (20 ml)
11. washThe xylene wash
12. extractionto re-extract the aqueous phase
13. stirringThe combined organic phases were stirred
14. temperatureheated
15. temperatureto reflux (85° C.) in a clean 500 ml 4-necked flask
16. customequipped with overhead stirrer, water condenser
17. additionEssochem solvent 30 (hydrocarbons Bp 100-130° C.) (100 ml) was added dropwise over 6 min
18. temperaturecool to ambient temperature
19. temperaturefurther cooled to −5° C.
20. filtrationThe product was filtered off
21. washwashed with Essochem solvent 30 (50 ml)
22. customThe cake was dried on the
23. filtrationfilter for 3 hours
24. customto give 15.20 g@100% strength, yield 76.8%

ORD 기록

ord-ff81cb763d1c43bcbc3abf6d0968d26a

출처 데이터셋

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07626020B2