Diisopropylethylamine → N'-(5-bromo-4-(4-chlorophenyl)pyridin-2-yl)-2-(6-(trifluoromethyl)pyridin-3-yl)acetohydrazide

Temperature

20 °C

To a suspension of 5-bromo-4-(4-chlorophenyl)-2-hydrazinylpyridine (37 mg, 0.12 mmol), 2-(6-(trifluoromethyl)pyridin-3-yl)acetic acid (26 mg, 0.12 mmol) and bromotripyrrolidinophosphonium hexafluorophosphate (PyBop, 70 mg, 0.13 mmol) in CH3CN (1.0 mL) was added (i-Pr)2EtN (32 mg, 0.25 mmol) at 20° C. The reaction mixture was stirred at 20° C. under argon for 15 h, then concentrated in vacuo. The residue was dissolved in EtOAc (15 mL). The organic solution was successively washed with saturated aqueous NaHCO3 (5 mL) and saturated aqueous NaCl (5 mL), dried over MgSO4, filtered and concentrated in vacuo. The residue was purified using reverse phase preparative HPLC (Conditions: Phemomenex Luna 5μ C18 30×75 mm; Eluted with 0% to 100% B, 10 min gradient, 100% B hold for 2 min, (A=90% H2O, 10% CH3CN, 0.1% trifluoroacetic acid and B=10% H2O, 90% CH3CN, 0.1% trifluoroacetic acid); Flow rate at 40 mL/min, UV detection at 220 nm), followed by basification with 1N aqueous NaOH to pH 12 and extraction with EtOAc to afford 54 mg (92%) of the title compound as a white solid. LC/MS (method B): retention time 1.91 min, [M+H]+=487.0.

1. concentrationconcentrated in vacuo
2. dissolutionThe residue was dissolved in EtOAc (15 mL)
3. washThe organic solution was successively washed with saturated aqueous NaHCO3 (5 mL) and saturated aqueous NaCl (5 mL)
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified
8. washEluted with 0% to 100% B, 10 min gradient, 100% B hold for 2 min
9. extractionFlow rate at 40 mL/min, UV detection at 220 nm), followed by basification with 1N aqueous NaOH to pH 12 and extraction with EtOAc

ORD record

ord-8f1d6815173f4b948e7194d9fdbde536

Source dataset

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07858639B2