Diisopropylethylamine → 1-(5-tert-Butyl-isoxazol-3-yl)-3-[5-fluoro-2-(1-isobutyl-1H-indazol-5-yloxy)-benzyl]-urea
Reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([CH2:20][CH:21]([CH3:23])[CH3:22])[N:15]=[CH:14]3)=[C:6]([CH:9]=1)[CH2:7][NH2:8].CCN(C(C)C)C(C)C.ClC(Cl)(O[C:37](=[O:43])OC(Cl)(Cl)Cl)Cl.[C:45]([C:49]1[O:53][N:52]=[C:51]([NH2:54])[CH:50]=1)([CH3:48])([CH3:47])[CH3:46]>ClCCl>[C:45]([C:49]1[O:53][N:52]=[C:51]([NH:54][C:37]([NH:8][CH2:7][C:6]2[CH:9]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=2[O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([CH2:20][CH:21]([CH3:23])[CH3:22])[N:15]=[CH:14]3)=[O:43])[CH:50]=1)([CH3:48])([CH3:47])[CH3:46]Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
To a cooled (0° C.) solution of 5-fluoro-2-(1-isobutyl-1H-indazol-5-yloxy)-benzylamine (0.364 g, 1.04 mmol) and DIEA (0.5 mL, 2.08 mmol) in dichloromethane (10 mL) was added triphosgene (0.131 g, 0.374 mmol). The mixture was stirred at 0° C. for 1 hour and then stirred at room temperature for 18 hours under N2 atmosphere. The reaction mixture was concentrated under reduced pressure and suspended in dichloromethane (10 mL) making a 0.123 M solution. 0.4 mL of this solution (0.015 g, 0.048 mmol) was treated with 5-tert-butyl-isoxazol-3-ylamine (0.008 g, 0.053 mmol). The product was obtained in 44% yield. MS (APCI+) m/z 480 (M+1) detected.
Workup
- stirringstirred at room temperature for 18 hours under N2 atmosphere
- concentrationThe reaction mixture was concentrated under reduced pressure
- customThe product was obtained in 44% yield
Sources & evidence
- ORD record
- ord-da6a2dbedfaa473c868dfca8f2d14131
- Source dataset
- uspto-grants-2009_04
- Patent number
- US07521447B2
Reaction notes
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