1,2-Dimethoxyethane → HCID 44231068, compound

Temperature

90 °C

A mixture of 4-(5-bromo-2-phenyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)pyridine (620 mg, 1.4 mmol; Example 1, Step 3), 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)pyridine-2-amine (570 mg, 2.3 mmol, Example 17, Step 3), and aqueous 2.0 M Na2CO3 solution (2 mL, 4 mmol) in DME (8 mL) was purged with Ar for 3 min. Pd(dppf) Cl2-DCM (34 mg, 0.04 mmol) was added and the reaction mixture was purged with Ar for another 5 min. The reaction mixture was then heated to and maintained at 90° C. for 18 h under Ar. The reaction was allowed to cool to rt and was concentrated. The resulting residue was suspended in EtOAc (15 mL) and passed through a syringe filter. The filtrate was concentrated, treated with aqueous 3 M HCl solution (6 mL), and heated at 60° C. for 2 h. The reaction was allowed to cool to rt and was evaporated in vacuo. The resulting residue was purified by reverse-phase HPLC and lypholized to afford 160 mg (33%) of 3-methoxy-5-(2-phenyl-5-(pyridine-4-yl)-1H-imidazol-4-yl)pyridine-2-amine as the TFA salt: LCMS (m/z): 344.2 (MH+); tR=0.46 min; 1H NMR (CD3OD) δ 3.88 (s, 3H), 6.22 (br s, 2H), 7.16 (m, 1H), 7.38 (t, J=7.2 Hz, 1H), 7.47 (t, J=7.2 Hz, 2H), 7.61 (m, 2H), 7.67 (m, 1H), 8.05 (d, J=6.0 Hz, 2H), 8.48 (d, J=6.0 Hz, 2H).

1. customwas purged with Ar for 3 min
2. customthe reaction mixture was purged with Ar for another 5 min
3. temperatureThe reaction mixture was then heated to and
4. temperatureto cool to rt
5. concentrationwas concentrated
6. custompassed through a syringe
7. filtrationfilter
8. concentrationThe filtrate was concentrated
9. additiontreated with aqueous 3 M HCl solution (6 mL)
10. temperatureheated at 60° C. for 2 h
11. temperatureto cool to rt
12. customwas evaporated in vacuo
13. customThe resulting residue was purified by reverse-phase HPLC

ORD record

ord-15e29f766d704ca0b3e13b54030aec04

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08865732B2