1,2,3-trifluoro-4-isocyanatobenzene

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: According to the method described in example S11, aminocarnitine (41 mg) was reacted with 1,2,3-trifluoro-4-isocyanatobenzene to yield the title compound as a white solid (2.3 mg). 1H NMR (400 MHz, CD3OD): δ=7.70-7.60 (m, 1H), 7.10-7.00 (m, 1H), 4.61 (br s, 1H), 3.80-45 (m, 2H), 3.22 (s, 9H), 2.40-2.60 (m, 2H), 1.97 (s, 3H); MS ESI [M+H]+, calcd for [C14H18F3N3O3+H]+ 334.3 found m/z 334.1 (100)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Using general method A, 1-(3-((t-butyldimethylsilyloxy)methyl)phenyl)-3-(2-fluorophenyl)-1H-pyrazol-5-amine (available from ethyl 3-(5-amino-3-(2-fluorophenyl)-1H-pyrazol-1-yl)benzoate using general method followed by protection with TBSCl) (0.4 g, 1.0 mmol) was combined with 2,3,4-trifluorophenyl isocyanate (0.32 g, 1.2 mmol) to yield 1-(2,3,4-trifluorophenyl)-3-(3-(2-fluorophenyl)-1-(3-(hydroxymethyl)phenyl)-1H-pyrazol-5-yl)urea (330 mg, 72% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.14 (brs, 1H), 9.01 (s, 1H), 7.98 (dt, J=1.6, and 8.0 Hz, 1H), 7.86 (m, 1H), 7.2-7.6 (m, 8H), 6.96 (d, J=4.0 Hz, 1H), 5.39 (t, J=6.0 Hz, 1H), 4.62 (d, J=6.0 Hz, 2H); MS (EI) m/z: 457.0 (M+H+).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1-(3-((t-butyldimethylsilyloxy)methyl)phenyl)-3-(thiophen-2-yl)-1H-pyrazol-5-amine (available from ethyl 3-(5-amino-3-(thiophen-2-yl)-1H-pyrazol-1-yl)benzoate using general method C followed by protection with TBSCl) (0.5 g, 1.3 mmol) in THF (3 mL) was added pyridine (0.10 g, 1.3 mmol) and 1,2,3-trifluoro-4-isocyanatobenzene (0.27 g, 1.6 mmol). The reaction mixture was stirred at room temperature for 22 hours. Water was added and the solid was filtered, washed with H2O and dried under vacuum to obtain the crude product. To a solution of the crude product in THF was added TBAF (1.6 mL, 1.0 M). The reaction mixture was stirred at room temperature for 3 hours. The solvent was removed under reduced pressure. Ethyl acetate was added into the residue and then 1N—HCl (5 drops) was added. The organic layer was washed with water, dried (Na2SO4) and evaporated under reduced pressure to obtain the crude product. The crude was dissolved in methanol and the solid filtered and dried under vacuum to yield 1-(1-(3-(hydroxymethyl)phenyl)-3-(thiophen-2-yl)-1H-pyrazol-5-yl)-3-(2,3,4-trifluorophenyl)urea (0.42 g, 73% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.13 (brs, 1H), 8.99 (s, 1H), 7.85 (m, 1H), 7.4-7.6 (m, 6H), 7.28 (m, 1H), 7.11 (dd, J=3.6, and 4.8 Hz, 1H), 6.86 (s, 1H), 5.39 (t, J=6.0 Hz, 1H), 4.62 (d, J=6.0 Hz, 2H); MS (EI) m/z: 445.0 (M+H+). the solid was filtered washed with H2O dried under vacuum to obtain the crude product The reaction mixture was stirred at room temperature for 3 hours The solvent was removed under reduced pressure Ethyl acetate was added into the residue 1N—HCl (5 drops) was added The organic layer was washed with water dried (Na2SO4) evaporated under reduced pressure to obtain the crude product the solid filtered dried under vacuum