Benzene, 1-chloro-3-isocyanato- → 1-(3-Chloro-propyl)-3-[4-(2-dimethylaminomethyl-imidazol-1-yl)-2-fluoro-phenyl]-urea
Reaction equation
[CH3:1][N:2]([CH2:4][C:5]1[N:6]([C:10]2[CH:15]=[CH:14][C:13]([NH2:16])=[C:12]([F:17])[CH:11]=2)[CH:7]=[CH:8][N:9]=1)[CH3:3].[Cl:18][C:19]1[CH:20]=[C:21]([N:25]=[C:26]=[O:27])C=CC=1>C(Cl)Cl>[Cl:18][CH2:19][CH2:20][CH2:21][NH:25][C:26]([NH:16][C:13]1[CH:14]=[CH:15][C:10]([N:6]2[CH:7]=[CH:8][N:9]=[C:5]2[CH2:4][N:2]([CH3:1])[CH3:3])=[CH:11][C:12]=1[F:17])=[O:27]Participants
Procedure
To a solution of 234.3 mg (1 mmol) of 4-(2-dimethylaminomethyl-imidazol-1-yl)-2-fluoro-phenylamine in 5 mL of anhydrous CH2Cl2 and under N2 atmosphere were added 179 mg (1.5 mmol) of 3-chlorophenylisocyanate. The mixture was stirred for 3 days at room temperature. The volatiles were concentrated to yield quantitatively 1-(3-chloro-propyl)-3-[4-(2-dimethylaminomethyl-imidazol-1-yl)-2-fluoro-phenyl]-urea as a viscous oil. This compound can be was used without further purification. 1H NMR (400 MHz, CDCl3) δ 8.25 (t, J=8.6 Hz, 1H), 7.44 (dd, J=9.7 Hz, and J=2.1 Hz, 1H), 7.25 (m, 1H), 7.13 (m, 1H), 7.065 (d, J=6.5 Hz, 1H), 5.65 (t, 1H), 3.65 (t, J=6.5 Hz, 2H), 3.47 (m, 2H), 3.38 (s, 2H), 2.24 (s, 6H), 2.05 (m, 2H), ppm. LC-MS (ESI) 354.0 [M+H]+, tR=2.51 min (Shimadzu Phenomenex S5 ODS 4.6×50 mm Luna flow rate 2.5 mL/mn; detection at 220 nM; Gradient elution 0% to 100% B over 8 min; (A=10% MeOH, 90% H2O, 0.2% H3PO4& B=90% MeOH, 10% H2O, 0.2% H3PO4). HRMS (ESI) m/z calcd for C16H22ClFN5O [M+H]+ 354.1497, found 354.1491.
Workup
- concentrationThe volatiles were concentrated
Sources & evidence
- ORD record
- ord-bb77df68b7124f25b27944d9496b449d
- Source dataset
- uspto-grants-2007_01
- Patent number
- US07169795B2
Reaction notes
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