Methane → HCID 86724303, compound

Temperature

100 °C

A mixture of di-tert-butyl (6′-bromo-2′,2′-dimethyldispiro[oxetane-3,3′-chromene-4′,4″-[1,3]thiazol]-2″-yl)imidodicarbonate (268 mg, 0.471 mmol), pyrimidin-5-ylboronic acid (175 mg, 1.41 mmol), bis(triphenylphosphine)palladium(II) dichloride (33.0 mg, 0.047 mmol) and Na2CO3 (150 mg, 1.41 mmol) in dioxane-water (4:1, 5.4 mL) was stirred for 1.5 hours at 100° C. Tetrakis(triphenylphosphine)palladium(0) (272 mg, 0.235 mmol) was added to the mixture and the mixture was stirred for 1.5 hours at 100° C. To the mixture was added charcoal and the mixture was stirred for 30 minutes at 50° C. The mixture was filtered through celite pad (eluted with EtOAc) and the filtrate was washed with water and brine. The organic layer was dried over MgSO4 and filtered, and the filtrate was concentrated at reduced pressure. To the residue were added toluene (2.7 mL) and silica gel (neutral; 804 mg), and the mixture was stirred for 1 hour at 110° C. After concentration of the reaction mixture at reduced pressure, the residue was purified with column chromatography on silica gel (CHCl3-EtOH, a linear gradient of EtOH from 0 to 20%), then re-purified with column chromatography on amino silica gel (Hexane-EtOAc, a linear gradient of EtOAc from 0 to 90%). The purified product was dissolved in dioxane (5.0 mL) and HCl (4 M in dioxane, 0.049 mL, 0.198 mmol) was added. The mixture was stirred for 2 hours at ambient temperature. After concentration at reduced pressure, the residue was triturated with IPE, collected by filtration and washed with IPE. The solid was dried under reduced pressure at 30° C. to afford 2′,2′-dimethyl-6′-(pyrimidin-5-yl)dispiro[oxetane-3,3′-chromene-4′,4″-[1,3]thiazol]-2″-amine hydrochloride (62.6 mg).

1. stirringthe mixture was stirred for 1.5 hours at 100° C
2. stirringthe mixture was stirred for 30 minutes at 50° C
3. filtrationThe mixture was filtered through celite pad (eluted with EtOAc)
4. washthe filtrate was washed with water and brine
5. dry with materialThe organic layer was dried over MgSO4
6. filtrationfiltered
7. concentrationthe filtrate was concentrated at reduced pressure
8. additionTo the residue were added toluene (2.7 mL) and silica gel (neutral; 804 mg)
9. stirringthe mixture was stirred for 1 hour at 110° C
10. customAfter concentration of the reaction mixture at reduced pressure, the residue was purified with column chromatography on silica gel (CHCl3-EtOH
11. customa linear gradient of EtOH from 0 to 20%), then re-purified with column chromatography on amino silica gel (Hexane-EtOAc
12. dissolutionThe purified product was dissolved in dioxane (5.0 mL)
13. stirringThe mixture was stirred for 2 hours at ambient temperature
14. concentrationAfter concentration at reduced pressure
15. customthe residue was triturated with IPE
16. filtrationcollected by filtration
17. washwashed with IPE
18. customThe solid was dried under reduced pressure at 30° C.

ORD record

ord-7cb145901b0747d8ac7cd63aa2ed19a7

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08975415B2