* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
INTERMEDIATE 37 4-(3 -Bromo-4-methyl- 1 H-pyrazol- 1 - yl)-2-methoxyp yridine To 3-bromo-4-methyl-lH-pyrazole (200 mg, 1.24 mmol) in DMSO (1.2 mL) at 0 C, was added sodium hydride (60% in mineral oil, 55 mg, 1.37 mmol). The reaction was warmed to 25 C and stirred for 60 min before 4-chloro-2-methoxypyridine (178 mg, 1.24 mmol) was added. The reaction mixture was stirred at 85 C overnight. The reaction mixture was quenched by the addition of water and was extracted with EtOAc. The combined organic extracts were dried over MgS04 and concentrated in vacuo. The crude mixture was purified by flash chromatography (ISCO Combiflash, 0-30% EtOAc in hexanes) to afford 4-(3-bromo-4-methyl-lH-pyrazol-l -yl)-2- methoxypyridine, as a white solid. LCMS calc. = 268.00; found = 267.99 (M+H)+. NMR (500 MHz, CDCI3): delta 8.16 (d, J= 5.8 Hz, 1 H); 7.69 (s, 1 H); 7.23-7.15 (m, 1 H); 6.95 (s, 1 H); 3.96 (s, 3 H); 2.08 (s, 3 H).
With trifluoroacetic acid; In dichloromethane; for 3.0h;
To a solution of 56 in MeCN was added N-bromosuccinimide (507 mg, 2.85 mmol). The reaction mixture was stirred for 18 h at room temperature. The reaction was worked-up with saturated NaHC03-EtOAc extraction. The crude product was purified by ISCO to afford 57 which was treated with TFA in CH2C12for 3 h to give 58 (120 mg, 39%).
To a solution of 58 (120 mg, 0.74 mmol) in dimethylformamide (DMF) (1 mL) was added NaH (40 mg, 1.6 mmol). The mixture was stirred for 0.5 h at room temperature and 2- bromo-l,3-thiazole (125 mg, 0.74 mmol) was added. The reaction mixture was stirred for 1 h at room temperature. The reaction temperature was raised to 90C and stirred overnight. The reaction was quenched with MeOH and solvent was removed in vacuo. The residue was treated with water and EtOAc. The organic layer was separated and aqueous was extracted with EtOAc. The combined organic phase was dried over a2S04, filtered, and concentrated to give crude product. The crude product was purified on ISCO columns. Fractions containing pure product were combined and evaporated to give 59 (67 mg, 37%) as a yellow solid.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
