تفاعل #168256

معادلة التفاعل

6-chloro-4-hydrazinyl-2-(4-phenoxyphenyl)nicotinonitrile

4-borono-2-fluorobenzoic acid

potassium phosphate

N2

→

desired product

4-(3-Amino-4-(4-phenoxyphenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl)-2-fluorobenzoic acid

المذيبات

DMF

ظروف التفاعل

الإجراء التجريبي

A solution of 6-chloro-4-hydrazinyl-2-(4-phenoxyphenyl)nicotinonitrile (9.5 mg, 0.028 mmol), 4-borono-2-fluorobenzoic acid (14.5 mg, 0.079 mmol), 2 M aqueous potassium phosphate (0.071 mL, 0.141 mmol) and PdCl2(dppf)-CH2Cl2 adduct (4.6 mg, 5.63 μmol) in DMF (0.45 mL) was degassed by vacuum-N2 refill cycle twice. The sealed tube was then heated at 85° C. under N2. After 1.5 h, no desired product was detected. Additional 4-borono-2-fluorobenzoic acid (21.4 mg), PdCl2(dppf)-CH2Cl2 adduct (11 mg), potassium phosphate (0.14 mL) and DMF (0.3 mL) were added. The mixture was again degassed by vacuum-N2 refill cycle twice and stirred at 85° C. for 20 h. The mixture was diluted with 1 N aqueous HCl (0.7 mL) and MeOH (0.8 mL), and purified by reverse phase HPLC (Sunfire S10 30×250 mm column), eluting with 60-90% solvent B (10% methanol-90% water-0.1% TFA) in solvent A (90% methanol-10% water-0.1% TFA), to give Example 245 as yellow powder (2.7 mg, 14% yield), assumed as bis-TFA salt. 1H NMR (400 MHz, methanol-d4) δ ppm 8.15 (1H, t, J=7.65 Hz), 7.89-7.93 (2H, m), 7.86 (1H, s), 7.77-7.84 (2H, m), 7.44-7.50 (2H, m), 7.24-7.30 (3H, m), 7.15-7.19 (2H, m); MS (ES+) m/z: 441.2 (M+H); LC retention time: 3.438 min (analytical HPLC Method A).

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