1,2-Cyclohexanedione → HCID 68182985, compound

In a 250 mL round bottomed flask were placed 1,2-cyclohexanedione (1.32 g, 11.8 mmol) and acetic acid (30 mL). To the solution was added dropwise a solution of bromine (1.67 g, 10.4 mmol) in acetic acid (20 mL). The mixture was stirred for 30 min at rt. To the mixture was added 2-methylpyrazolo[1,5-a]pyridine-3-carbothioamide (1.92 g, 10.0 mmol) and the resulting suspension was stirred for 1 hr at 120° C. After 30 min the suspension turned into a clear brown solution. After 1 hour the mixture was allowed to cool to rt during which time an off-white solid precipitated. The mixture was concentrated under reduced pressure and the residue was diluted with EtOAc (100 mL) and a saturated aqueous solution of NaHCO3 (100 mL). The resulting bi-phasic mixture was vigorously stirred for 30 min at rt. The aqueous phase was separated and the organic phase was washed with a 10% aqueous solution of NaHSO3 (50 mL), then a saturated aqueous solution of NaHCO3 (50 mL). The organic phase was dried over anhydrous MgSO4. Insoluble materials were removed by filtration and the filtrate was concentrated under reduced pressure. The residue was recrystallized from EtOAc and ether to yield the title compound (1.0 g; 35%) as a yellowish off-white crystalline solid. From the mother liquor, a 2nd crop of title compound (1.5 g; 53%) was obtained. LCMS: (FA) ES+ 284; 1H NMR (400 MHz, d6-DMSO) δ ppm 8.75 (dt, 1H), 8.29 (dt, 1H), 7.54 (dd, 1H), 7.07 (td, 1H), 3.16 (t, 2H), 2.65 (s, 3H), 2.60 (dd, 2H), 2.14-2.21 (m, 2H).

1. customIn a 250 mL round bottomed flask were placed
2. stirringthe resulting suspension was stirred for 1 hr at 120° C
3. waitAfter 30 min the suspension turned into a clear brown solution
4. waitAfter 1 hour the mixture was allowed
5. temperatureto cool to rt during which time an off-white solid
6. customprecipitated
7. concentrationThe mixture was concentrated under reduced pressure
8. additionthe residue was diluted with EtOAc (100 mL)
9. stirringThe resulting bi-phasic mixture was vigorously stirred for 30 min at rt
10. customThe aqueous phase was separated
11. washthe organic phase was washed with a 10% aqueous solution of NaHSO3 (50 mL)
12. dry with materialThe organic phase was dried over anhydrous MgSO4
13. customInsoluble materials were removed by filtration
14. concentrationthe filtrate was concentrated under reduced pressure
15. customThe residue was recrystallized from EtOAc and ether

ORD record

ord-a099e8afa5454c92a0b1d4d4f129aed7

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08765746B2