Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:17][C:18](=[O:23])[CH2:19][C:20](=O)[CH3:21])[CH:5]=[CH:6][C:7]=1[NH:8][CH2:9][CH2:10][CH2:11][CH:12]1[CH2:16][CH2:15][CH2:14][O:13]1.[C:24]([NH2:27])(=O)[CH3:25].C1(C)C(C)=CC=CC=1.[NH4+].[Cl-]>C([O-])(C)C.C([O-])(C)C.C([O-])(C)C.C([O-])(C)C.[Ti+4].C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([N:17]2[C:18](=[O:23])[CH:19]=[C:20]([CH3:21])[N:27]=[C:24]2[CH3:25])[CH:5]=[CH:6][C:7]=1[NH:8][CH2:9][CH2:10][CH2:11][CH:12]1[CH2:16][CH2:15][CH2:14][O:13]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 165 °C
Procedure
A mixture of N-(3-fluoro-4-((3-(tetrahydrofuran-2-yl)propyl)amino)phenyl)-3-oxobutanamide (250 mg, 0.78 mmol), acetamide (92 mg, 1.56 mmol), titanium tetraisopropanolate (1.9 mL) and xylene (10 mL) was stirred at 165° C. for 24 h. The mixture was then cooled to rt. 60 mL of toluene and 60 mL of saturated NH4Cl aqueous solution were added and the resulting mixture was stirred further at rt overnight. The mixture was then filtered and the filtrate was extracted with DCM (15 mL×3). The combined organic layers were washed with brine (15 mL×2), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=1:2) to give the title compound as a yellow solid (80 mg, 29%). The compound was characterized by the following spectroscopic data:
Workup
- temperatureThe mixture was then cooled to rt
- stirringthe resulting mixture was stirred further at rt overnight
- filtrationThe mixture was then filtered
- extractionthe filtrate was extracted with DCM (15 mL×3)
- washThe combined organic layers were washed with brine (15 mL×2)
- dry with materialdried over anhydrous Na2SO4
- concentrationconcentrated in vacuo
- customThe residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=1:2)
Sources & evidence
- ORD record
- ord-3dbf39e8ebda4244a9c3ea891f60787c
- Source dataset
- uspto-grants-2016_09
- Patent number
- US09434695B2
Linked notes
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