Benzyl Bromide → HCID 67353995, compound

Temperature

100 °C

To a stirred solution containing 4.87 g (17.4 mmol) of 5-bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl)-4,6-dimethylpyrimidine in 50 mL of 1:1 dioxane-degassed water was added 632 mg (0.69 mmol) of Pd2dba3 followed by 293 mg (0.69 mmol) of 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (L1) and 2.92 g (52.1 mmol) of KOH. The reaction mixture was stirred at 100° C. for 3 h. The cooled reaction mixture was poured into 200 mL of water and extracted with 100 mL of ethyl acetate. The aqueous layer was acidified with HCl (pH 2-3) and then extracted with two 150-mL portions of ethyl acetate. The combined organic layer was washed with 150 mL of brine, dried (MgSO4) and concentrated under diminished pressure. The residue was dissolved in 50 mL of anhydrous THF and treated with 3.10 mL (26.0 mmol) of benzyl bromide followed by 1.40 g (34.8 mmol) of a 60% suspension of NaH in mineral oil. The reaction mixture was stirred at 23° C. for 48 h. The reaction mixture was quenched with satd aq sodium bicarbonate and poured into 150 mL of water and extracted with two 150-mL portions of ether. The combined organic layer was washed with 150 mL of brine, dried (MgSO4) and concentrated under diminished pressure. The residue was purified by chromatography on a silica gel column (20×6 cm). Elution with 9:1 hexanes-ethyl acetate afforded the expected product as a light yellow oil: yield 4.09 g (76%); silica gel TLC Rf 0.6 (6:1 hexanes-ethyl acetate); 1H NMR (CDCl3) δ2.29 (s, 6H), 2.47 (s, 6H), 4.92 (s, 2H), 5.86 (s, 2H) and 7.42 (m, 5H); 13C NMR (CDCl3) δ 14.1, 14.1, 19.1, 19.1, 75.3, 107.9, 107.9, 128.3, 128.6, 128.6, 129.0, 129.0, 129.2, 129.2, 136.0, 147.7, 152.3, 152.3 and 161.6; mass spectrum (APCI), m/z 307.1675 (M)+ (C19H21N3O requires 307.1685).

1. customdegassed water
2. customThe cooled reaction mixture
3. extractionextracted with 100 mL of ethyl acetate
4. extractionextracted with two 150-mL portions of ethyl acetate
5. washThe combined organic layer was washed with 150 mL of brine
6. dry with materialdried (MgSO4)
7. concentrationconcentrated under diminished pressure
8. dissolutionThe residue was dissolved in 50 mL of anhydrous THF
9. stirringThe reaction mixture was stirred at 23° C. for 48 h
10. customThe reaction mixture was quenched with satd aq sodium bicarbonate
11. additionpoured into 150 mL of water
12. extractionextracted with two 150-mL portions of ether
13. washThe combined organic layer was washed with 150 mL of brine
14. dry with materialdried (MgSO4)
15. concentrationconcentrated under diminished pressure
16. customThe residue was purified by chromatography on a silica gel column (20×6 cm)
17. washElution with 9:1 hexanes-ethyl acetate

ORD record

ord-7f57fcdc530a4ad88e1efbd2c31c1aa8

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952025B2