Sorafenib Impurity 13 synthesis

Yield:583840-04-4 51%

Reaction Conditions:

in BAY 67-3472;

Steps:

2.4 Step 4

Step 4 Preparation of N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-{4-[2-carbamoyl-1-oxo-(4-pyridyloxy)]phenyl}urea N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-{4-[2-carbamoyl-1-oxo-(4-pyridyloxy)]phenyl}urea (125.6 mg, 51%) was prepared as a white solid from N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-{4-[2-carbamoyl-(4-pyridyloxy)]phenyl}urea (240.0 mg, 0.53 mmol), in the manner described for N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-{4-[2-(N-methylcarbamoyl)-1-oxo-(4-pyridyloxy)]phenyl}urea: TLC (5% MeOH/CH₂Cl₂) R_f 0.17; ¹H-NMR (DMSO-d₆) δ 10.72 (d, J=4.3 Hz, 1H), 9.21 (s, 1H), 8.99 (s, 1H), 8.36 (d, J=7.2 Hz, 1H), 8.31 (d, J=4.1 Hz, 1H), 8.10 (d, J=2.3 Hz, 1H), 7.65 (dd, J=8.7 Hz, 2.3 Hz, 1H), 7.60 (d, J=8.9 Hz, 1H), 7.57 (d, J=9.0 Hz, 2H), 7.54 (d, J=3.8 Hz, 1H), 7.28 (dd, J=7.2 Hz, 3.8 Hz, 1H), 7.18 (d, J=9.0 Hz, 2 H); HPLC EI-MS m/z 467 ((M+H)⁺; Anal. calcd for C₂₀H₁₄ClF₃N₄O₄ 0.5H₂O: C, 50.49%; H, 3.18%; N, 11.78%. Found. C, 50.69%; H, 2.86%; N, 11.47%.

References:

US2003/216446,2003,A1