Potassium Carbonate → HCID 71519587, compound

Temperature

100 °C

A suspension of (1R,2S,3R)-3-((6-((5-iodo-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexane-1,2-diol (120 mg, 0.2 mmol), vinylboronic acid pinacol ester (71 mg, 0.5 mmol), and K2CO3 (64 mg, 0.5 mmol) in 6:1 dioxane:water (3.5 mL) was purged with argon for 5 min. [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (II) (19 mg, 0.02 mmol) was added to the mixture, the mixture was purged with argon for an additional 5 min and then heated in a sealed tube at 100° C. for 6 h. The mixture was cooled to rt and partitioned between EtOAc (150 mL) and 0.5 M aq K2CO3 (100 mL). The organic layer was separated and washed with brine (100 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by reverse-phase preparative HPLC using a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase to afford the nearly pure compound. This was further purified by silica gel flash chromatography, eluting isocratically with 5% MeOH in CH2Cl2, to afford (1R,2S,3R)-3-((6-((5-vinyl-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexane-1,2-diol (5 mg, 5%) as a white powder. 1H NMR (500 MHz, MeOH-d4) δ 8.28 (br s, 1H), 7.69 (s, 1H), 7.54 (m, 1H), 7.41-7.43 (m, 2H), 7.37 (d, J=8.1 Hz, 1H), 7.22 (m, 1H), 6.81-6.86 (m, 2H), 5.76 (d, J=17.7 Hz, 1H), 5.49 (s, 2H), 5.19 (d, J=11.1 Hz, 1H), 3.99-4.02 (m, 2H), 3.50 (m, 1H), 2.08 (m, 1H), 1.72-1.85 (m, 2H), 1.48-1.55 (m, 2H), 1.28-1.39 (m, 2H); LCMS (ESI) m/z 421 (M+H)+.

1. additionwas added to the mixture
2. customthe mixture was purged with argon for an additional 5 min
3. temperatureThe mixture was cooled to rt
4. custompartitioned between EtOAc (150 mL) and 0.5 M aq K2CO3 (100 mL)
5. customThe organic layer was separated
6. washwashed with brine (100 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by reverse-phase preparative HPLC
11. additiona mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase
12. customto afford the nearly pure compound
13. customThis was further purified by silica gel flash chromatography
14. washeluting isocratically with 5% MeOH in CH2Cl2

ORD record

ord-72b4e862180d4274aaf864f748888bf3

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952058B2