Triethylamine → 2-Fluoro-N1-(4-fluorobenzyl)-4-nitrobenzene-1,3-diamine

Temperature

120 °C

To a stirred suspension of compound 2 (0.100 g, 0.570 mmol, 1.00 equiv) in dry DMSO (4.6 mL) were added 4-fluorobenzylamine (0.210 g, 1.72 mmol, 3.00 equiv) followed by Et3N (69.6 mg, 0.690 mmol, 1.20 equiv) and I2 (catalytic, 1.00 mg). The reaction mixture was heated to 120° C. and stirred at 120° C. for 24 h. After consumption of the starting material (by TLC), the reaction mixture was cooled to RT, diluted with water (25 mL) and extracted with EtOAc (2×25 mL). The separated organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give crude; which was purified by silica gel column chromatography (EtOAc/Hexane 2:23) to afford compound 3 (0.100 g, 62.5%) as yellow solid. TLC: 20% EtOAc/Hexane (Rf: 0.20); 1H NMR (400 MHz, CDCl3): δ 7.87 (dd, J=1.60, 9.60 Hz, 1H), 7.31-7.28 (m, 2H), 7.08-7.03 (m, 2H), 6.11-6.03 (m, 3H, 2Exc), 4.82 (br s, 1H, Exc), 4.44 (d, J=5.2 Hz, 2H); LC-MS: m/z=278 (M+-1) at RT 3.64 (91.7% purity)

1. customAfter consumption of the starting material (by TLC)
2. temperaturethe reaction mixture was cooled to RT
3. additiondiluted with water (25 mL)
4. extractionextracted with EtOAc (2×25 mL)
5. dry with materialThe separated organic layer was dried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customto give crude
9. customwhich was purified by silica gel column chromatography (EtOAc/Hexane 2:23)

ORD record

ord-2e0b0cf99cc846658419a24c16a8256a

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08916133B2