Tetrahydrofuran → HCID 10335345, compound

A clean, dry, 1 liter 4 neck round bottom flask equipped with mechanical stirrer, temperature probe, and purged with nitrogen, was charged with 6-[oxazol-5-yl]-3-isopropyl[1,2,4]triazolo[4,3-a)pyridine (45.2 grams 0.198 moles) and dimethylformamide (271 ml). The pot was cooled below −60° C. with a dry icelacetone bath. Lithium bis(trimethylsilyl)amide, 1 molar solution in tetrahydrofuran (198 ml 0.198 moles), was added, keeping the temperature below −60° C. After the addition was complete, the pot was further cooled to below −70° C. and stirred for 1 hour. While stirring, a solution of N-bromosuccinimide (35.24 g 0.198 moles) and dimethylformamide (105 ml), were stirred in a separate 500 ml round bottom flask under nitrogen. After the one hour stir at −70° C., the solution of N-bromosuccinimide and dimethylformamide was slowly added to the anion keeping the temperature below −70° C. After the addition, the reaction was continued for one hour below −70° C. The batch was then warmed to room temperature and quenched into methylene chloride (452 ml) and 1 N sodium hydroxide (452 ml). The organic layer was then separated. The aqueous layer was extracted a second time with methylene chloride (135 ml). The combined organic phase was washed with 1 N sodium hydroxide (452 ml) and saturated brine solution (452 ml). The organic phase was then dried over magnesium sulfate (50 grams) and concentrated/displaced with isopropyl ether (226 ml) to a temperature of 42° C. A thick slurry formed upon cooling. The solids were granulated at 20 to 25° C. for two hours, filtered, washed with isopropyl ether (50 ml), and dried to afford 53.0 grams of light yellow solids, 96.4% purity (HPLC), 87% of theory.

1. customA clean, dry
2. custom1 liter 4 neck round bottom flask equipped with mechanical stirrer
3. customtemperature probe, and purged with nitrogen
4. temperatureThe pot was cooled below −60° C. with a dry icelacetone bath
5. customthe temperature below −60° C
6. additionAfter the addition
7. temperaturethe pot was further cooled to below −70° C.
8. stirringWhile stirring
9. stirringAfter the one hour stir at −70° C.
10. customthe temperature below −70° C
11. additionAfter the addition
12. waitthe reaction was continued for one hour below −70° C
13. customquenched into methylene chloride (452 ml) and 1 N sodium hydroxide (452 ml)
14. customThe organic layer was then separated
15. extractionThe aqueous layer was extracted a second time with methylene chloride (135 ml)
16. washThe combined organic phase was washed with 1 N sodium hydroxide (452 ml) and saturated brine solution (452 ml)
17. dry with materialThe organic phase was then dried over magnesium sulfate (50 grams) and concentrated/displaced with isopropyl ether (226 ml) to a temperature of 42° C
18. customA thick slurry formed
19. temperatureupon cooling
20. waitThe solids were granulated at 20 to 25° C. for two hours
21. filtrationfiltered
22. washwashed with isopropyl ether (50 ml)
23. customdried

ORD record

ord-7fac671039cc45d193a37a3f9b45325d

Source dataset

uspto-grants-2006_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07012143B2