1,10-Phenanthroline → Ethyl 4-(2-(ethyl(methyl)carbamoyl)pyrimidin-5-yloxy)-2-methylbenzofuran-6-carboxylate
Reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([C:8]([N:10]([CH2:12][CH3:13])[CH3:11])=[O:9])=[N:6][CH:7]=1.[OH:14][C:15]1[C:20]2[CH:21]=[C:22]([CH3:24])[O:23][C:19]=2[CH:18]=[C:17]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH:16]=1.C([O-])([O-])=O.[Cs+].[Cs+].N1C2C(=CC=C3C=2N=CC=C3)C=CC=1>[Cu](I)I.CN(C)C=O>[CH2:12]([N:10]([CH3:11])[C:8]([C:5]1[N:4]=[CH:3][C:2]([O:14][C:15]2[C:20]3[CH:21]=[C:22]([CH3:24])[O:23][C:19]=3[CH:18]=[C:17]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH:16]=2)=[CH:7][N:6]=1)=[O:9])[CH3:13]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 90 °C
Procedure
The flask was charged with 5-bromo-N-ethyl-N-methylpyrimidine-2-carboxamide (SM-3: 615 mg, 2.5 mmol), ethyl 4-hydroxy-2-methylbenzofuran-6-carboxylate (I-1c: 378 mg, 1.7 mmol), Cs2CO3 (1.15 g, 3.5 mmol), 1,10-phenanthroline (30.3 mg, 0.17 mmol), copper iodide (16 mg, 0.08 mmol) and dimethylformamide (17 mL). The reaction mixture was degassed with N2 for 5 minutes and then heated to 90° C. for 16 hours under a N2 atmosphere. The reaction mixture was diluted with ethylacetate (250 mL), washed with water (3×100 mL), dried (MgSO4) and concentrated. The crude material was purified by a biotage 50 g silica gel column (20%-100% EtOAc in Hep) to afford the title compound ethyl 4-(2-(ethyl(methyl)carbamoyl)pyrimidin-5-yloxy)-2-methylbenzofuran-6-carboxylate (I-5a: 180 mg, 28%) as a yellow solid.
Workup
- customThe reaction mixture was degassed with N2 for 5 minutes
- additionThe reaction mixture was diluted with ethylacetate (250 mL)
- washwashed with water (3×100 mL)
- dry with materialdried (MgSO4)
- concentrationconcentrated
- customThe crude material was purified by a biotage 50 g silica gel column (20%-100% EtOAc in Hep)
Sources & evidence
- ORD record
- ord-ff4acfd8b6a74cfe97a427a7a0523978
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08735396B2
Reaction notes
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