Diisopropylethylamine → N1-(3-Fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-phenylmalonamide
Reaction equation
[O:1]=[C:2]([NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH2:3][C:4](O)=[O:5].C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.[F:29][C:30]1[CH:31]=[C:32]([CH:34]=[CH:35][C:36]=1[O:37][C:38]1[CH:43]=[CH:42][N:41]=[C:40]2[CH:44]=[C:45]([I:47])[S:46][C:39]=12)[NH2:33].CCN(C(C)C)C(C)C>C(Cl)Cl>[F:29][C:30]1[CH:31]=[C:32]([NH:33][C:4](=[O:5])[CH2:3][C:2]([NH:7][C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[O:1])[CH:34]=[CH:35][C:36]=1[O:37][C:38]1[CH:43]=[CH:42][N:41]=[C:40]2[CH:44]=[C:45]([I:47])[S:46][C:39]=12Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of the acid 1 (465 mg, 2.59 mmol) and BOPCl (666 mg, 2.59 mmol) was mixed in DCM (5 mL) at 0° C. and stirred at the same temperature for 15 min. The reaction mixture was then treated with a solution of 410 (500 mg, 1.29 mmol) and iPr2NEt (1.3 mL, 1 g, 7.79 mmol) in DCM (5 mL) at 0° C. and allowed to stir at room temperature for overnight. The mixture was diluted in DCM (30 mL), washed with saturated NaHCO3 solution (30 mL), dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by flash chromatography using the gradient 75-100% EtOAc in hexanes as an eluent, to provide 411 (382 mg, 54% yield). 1H NMR 6 (400 MHz, CD3OD): 8.33 (d, 5.7 Hz), 7.79 (dd, 1H, J=2.4 Hz, J=12.3 Hz), 7.54 (m, 5H), 7.2-7.4 (m, 4H), 7.09 (t, 1H, J=7.2 Hz), 6.50 (d, 1H, J=5.5 Hz), 3.51 (s, 2H), 7.75 (s, 1H). MS (m/z): (M+1) 547.9 (100%).
Workup
- stirringto stir at room temperature for overnight
- washwashed with saturated NaHCO3 solution (30 mL)
- dry with materialdried over anhydrous Na2SO4
- filtrationfiltered
- concentrationconcentrated
- customThe residue was purified by flash chromatography
Sources & evidence
- ORD record
- ord-895febdcd21e4e839e76e0e36f50ccad
- Source dataset
- uspto-grants-2012_12
- Patent number
- US08329726B2
Reaction notes
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